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Sample records for sustained antinociceptive effect

Antinociceptive effect of purine nucleotides.

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Mello, C F; Begnini, J; De-La-Vega, D D; Lopes, F P; Schwartz, C C; Jimenez-Bernal, R E; Bellot, R G; Frussa-Filho, R

1996-10-01

The antinociceptive effect of purine nucleotides administered systematically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that antinociceptive effect of adenine nucleotides is mediated by adenosine.
Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice.

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Ghosh, Sudeshna; Kinsey, Steven G; Liu, Qing-Song; Hruba, Lenka; McMahon, Lance R; Grim, Travis W; Merritt, Christina R; Wise, Laura E; Abdullah, Rehab A; Selley, Dana E; Sim-Selley, Laura J; Cravatt, Benjamin F; Lichtman, Aron H

2015-08-01

Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception but with minimal cannabimimetic side effects. Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents another challenge in this potential therapeutic strategy. Therefore, the present study tested whether full FAAH inhibition combined with partial MAGL inhibition would produce sustained antinociceptive effects with minimal cannabimimetic side effects. Accordingly, we tested a high dose of the FAAH inhibitor PF-3845 (N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide; 10 mg/kg) given in combination with a low dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (4 mg/kg) in mouse models of inflammatory and neuropathic pain. This combination of inhibitors elicited profound increases in brain AEA levels (>10-fold) but only 2- to 3-fold increases in brain 2-AG levels. This combination produced significantly greater antinociceptive effects than single enzyme inhibition and did not elicit common cannabimimetic effects (e.g., catalepsy, hypomotility, hypothermia, and substitution for Δ(9)-tetrahydrocannabinol in the drug-discrimination assay), although these side effects emerged with high-dose JZL184 (i.e., 100 mg/kg). Finally, repeated administration of this combination did not lead to tolerance to its antiallodynic actions in the carrageenan assay or CB1 receptor functional tolerance. Thus, full FAAH inhibition
Toxicity and antinociceptive effects of Hamelia patens

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Angel Josabad Alonso-Castro

Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.
The antinociceptive effect of zolpidem and zopiclone in mice.

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Pick, Chaim G; Chernes, Yakov; Rigai, Tova; Rice, Kenner C; Schreiber, Shaul

2005-07-01

Zolpidem and zopiclone are two of a newer hypno-sedative class of drugs, the "Z compounds". Their use for the treatment of short-term insomnia has been expanding constantly during the last two decades. The "Z compounds" are considered to cause less significant rebound insomnia or tolerance than the conventional hypnotic benzodiazepines. Their possible antinociceptive effect and interaction with the opioid system has not been studied yet. Our results demonstrate a significant difference between the antinociceptive properties of zopiclone and zolpidem when injected s.c. in the hotplate analgesic assay in mice. Zopiclone induced a weak, dose-dependent antinociceptive effect, antagonized only by the alpha2-adrenergic receptor antagonist yohimbine. Zolpidem induced a weak, biphasic dose-dependent antinociceptive effect, antagonized primarily by the non-selective opioid antagonist naloxone and by yohimbine. The weak antinociceptive effect of both drugs, evident only at very high doses (far beyond those used clinically to induce sleep), implies no clinical use for zopiclone or zolpidem in the management of pain. However, the possible interaction of zolpidem with the opioid system should be further investigated (in behavioral models, which do not overlap with the acute-pain antinociception model we used), both for possible side effects in special populations (i.e. elderly) and for possible drug-drug interactions, in order to minimize possible hazards and maximize clinical beneficial effects of its use for sleep.
Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

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Abdel Salam, Omar M E

2006-01-01

The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.
The effect of benfotiamine on mu-opioid receptor mediated antinociception in experimental diabetes.

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Nacitarhan, C; Minareci, E; Sadan, G

2014-03-01

Diabetic neuropathy is a prevalent, disabling disorder. Currently, the only treatments available to patients with diabetic neuropathy are glucose control and pain management. B vitamin present neuroprotective effects, which are suggested to be related to their analgesic action in various models of neuropathic pain. According to our literature knowledge there is no report about antinociceptive effects of thiamine as benfotiamine and opioids together in diabetic mice. The purpose of this study was to determine the effects of benfotiamine on the antinociception produced by mu-opioid receptor agonist fentanyl in diabetic mice. The effects of benfotiamine on antinociception produced by fentanyl in diabetic mice were studied in 4 groups. Antinociceptive effect was determined with tail flick, hot plate and formalin test. Our results showed that, mu-opioid agonist fentanyl in benfotiamine applied diabetic group caused more potent antinociceptive effect than in diabetic group without benfotiamine treatment. In brief benfotiamine supplement in diet did not bring out antinociceptive effect itself, but during development of STZ diabetes, benfotiamine replacement increased the antinociceptive effect of fentanyl in mice tail-flick test. This effect is probably due to the replacement of benfotiamine efficiency occurring in diabetes mellitus. Finally, we suppose that oral benfotiamine replacement therapy may be useful to ameliorate analgesic effect of mu-opioid agonists on neuropathic pain in diabetic case. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.
Antinociceptive effect of novel pyrazolines in mice

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Tabarelli Z.

2004-01-01

Full Text Available The antinociceptive effect of six novel synthetic pyrazolines (3-ethoxymethyl-5-ethoxycarbonyl-1H-pyrazole (Pz 1 and its corresponding 1-substituted methyl (Pz 2 and phenyl (Pz 3 analogues, and 3-(1-ethoxyethyl-5-ethoxycarbonyl-1H-pyrazole (Pz 4 and its corresponding 1-substituted methyl (Pz 5 and phenyl (Pz 6 analogues was evaluated by the tail immersion test in adult male albino mice. The animals (N = 11-12 in each group received vehicle (5% Tween 80, 10 ml/kg, sc or 1.5 mmol/kg of each of the pyrazolines (Pz 1-Pz 6, sc. Fifteen, thirty and sixty minutes after drug administration, the mice were subjected to the tail immersion test. Thirty minutes after drug administration Pz 2 and Pz 3 increased tail withdrawal latency (vehicle = 3.4 ± 0.2; Pz 2 = 5.2 ± 0.4; Pz 3 = 5.9 ± 0.4 s; mean ± SEM, whereas the other pyrazolines did not present antinociceptive activity. Dose-effect curves (0.15 to 1.5 mmol/kg were constructed for the bioactive pyrazolines. Pz 2 (1.5 mmol/kg, sc impaired motor coordination in the rotarod and increased immobility in the open-field test. Pz 3 did not alter rotarod performance and spontaneous locomotion, but increased immobility in the open field at the dose of 1.5 mmol/kg. The involvement of opioid mechanisms in the pyrazoline-induced antinociception was investigated by pretreating the animals with naloxone (2.75 µmol/kg, sc. Naloxone prevented Pz 3- but not Pz 2-induced antinociception. Moreover, naloxone pretreatment did not alter Pz 3-induced immobility. We conclude that Pz 3-induced antinociception involves opioid mechanisms but this is not the case for Pz 2.
Antinociceptive effects of Cremophor EL orally administered to mice

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Z. Tabarelli

2003-01-01

Full Text Available Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight or saline (0.9% NaCl, 10 ml/kg body weight. CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL.
TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate.

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Rios, Emiliano Ricardo Vasconcelos; Rocha, Nayrton Flávio Moura; Carvalho, Alyne Mara Rodrigues; Vasconcelos, Leonardo Freire; Dias, Marília Leite; de Sousa, Damião Pergentino; de Sousa, Francisca Cléa Florenço; Fonteles, Marta Maria de França

2013-05-25

Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT. The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists. CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT. The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
[Genetic and environmental effects on neuromodulation and the antinociceptive effect of dextromethorphan].

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Oestreicher, M K; Desmeules, J; Piguet, V; Allaz, A F; Dayer, P

1998-02-07

Administration of NMDA antagonists leads to attenuation or disappearance of some symptoms of central sensitization, such as secondary hyperalgesia. However, the side effects of NMDA antagonists to a large extent counterbalance the expected benefits, thus preventing wide or prolonged use. Dextromethorphan and its metabolite dextrophan, on the other hand, are established and safe drugs. Experimentally they both antagonize the NMDA receptor. This study evaluates the effects of dextromethorphan and its metabolite in pain models using electrical stimulation for testing the antinociceptive effect and capsaicin-induced hyperalgesia. Dextromethorphan shows clear antinociceptive as well as neuromodulary effects, both depending heavily on the cytochrome P450 2D6 phenotype (CYP2D6).
Comparative antinociceptive and sedative effects of epidural romifidine and detomidine in buffalo (Bubalus bubalis).

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Marzok, M A; El-Khodery, S A

2017-07-01

In this study, comparative antinociceptive and sedative effects of epidural administration of romifidine and detomidine in buffalo were evaluated. Eighteen healthy adult buffalo, allocated randomly in three groups (two experimental and one control; n=6) received either 50 μg/kg of romifidine or detomidine diluted in sterile saline (0.9 per cent) to a final volume of 20 ml, or an equivalent volume of sterile saline epidurally. Antinociception, sedation and ataxia parameters were recorded immediately after drug administration. Epidural romifidine and detomidine produced mild to deep sedation and complete antinociception of the perineum, inguinal area and flank, and extended distally to the coronary band of the hindlimbs and cranially to the chest area. Times to onset of antinociception and sedation were significantly shorter with romifidine than with detomidine. The antinociceptive and sedative effects were significantly longer with romifidine than with detomidine. Romifidine or detomidine could be used to provide a reliable, long-lasting and cost-effective method for achieving epidural anaesthesia for standing surgical procedures in buffalo. Romifidine induces a longer antinociceptive effect and a more rapid onset than detomidine. Consequently, epidural romifidine may offer better therapeutic benefits in the management of acute postoperative pain. British Veterinary Association.
Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

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Okuyama, S; Aihara, H

1987-02-01

The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.
Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

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Mohammad Reza Zarrindast

2009-04-01

Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p. and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.
PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

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Tsuda Yuko

2010-12-01

Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.
Chemical composition and antinociceptive effects of essential oil ...

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Antinociceptive effect of EOGT in rats was carried out using chemical (formalin and acetic acid) and .... rat using a microsyringe with a 27 gauge needle. Immediately after formalin ... SEM, and were analyzed using GraphPad Prism. Statistically ...
Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae

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Raimundo Gonçalves de Oliveira Júnior

2017-05-01

Full Text Available Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p., a medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (E-caryophyllene, caryophyllene oxide, and camphor. The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (p < 0.05. The same was observed in both phases (neurogenic and inflammatory of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of KATP channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4. These results corroborate the medicinal use of C. conduplicatus in folk medicine.
Dextromethorphan differentially affects opioid antinociception in rats

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Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

2005-01-01

Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510
Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae Exert Antinociceptive and Neuropharmacological Effects in Mice

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Md. Shafiullah Shajib

2018-02-01

Full Text Available Polymethoxylavones (PMFs are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1, 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin (2, 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3, and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4, isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w. exhibited dose-dependent and significant (p < 0.01 antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w. demonstrated significant (p < 0.05 anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4 from N. Plumbaginifolia could be considered as suitable candidates for the development
Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

2012-08-01

To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.
alpha-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception.

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Sierralta, F; Naquira, D; Pinardi, G; Miranda, H F

1996-10-01

1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.

Serotonin induces peripheral antinociception via the opioidergic system.

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Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda E; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

2018-01-01

Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model. The selective antagonists for mu, delta and kappa opioid receptors, clocinnamox clocinnamox (40 μg), naltrindole (60 μg) and nor-binaltorfimina (200 μg), respectively, inhibited the antinociceptive effect induced by serotonin. Additionally, bestatin (400 μg), an inhibitor of enkephalinases that degrade peptides opioids, enhanced the antinociceptive effect induced by serotonin (low dose of 62.5 ng). These results suggest that serotonin possibly induce peripheral antinociception through the release of endogenous opioid peptides, possible from immune cells or keratinocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Differential effects of whole-body γ-irradiation on antinociception induced by morphine and β-endorphin administered intracerebroventricularly in the mouse

International Nuclear Information System (INIS)

Kim, J.K.; Chung, K.M.; Park, T.W.

2000-01-01

Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a μ-opioid receptor agonist) and β-endorphin (an ε-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, γ-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a δ-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of γ-irradiation on the antinociception produced by i.c.v. injected morphine and β-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a 60 Co γ-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or β-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by β-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of μ- and ε-opioid receptors to γ-irradiation, in addition, support the hypothesis that morphine and β-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)
Differential effects of whole-body {gamma}-irradiation on antinociception induced by morphine and {beta}-endorphin administered intracerebroventricularly in the mouse

Energy Technology Data Exchange (ETDEWEB)

Kim, J.K. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of); Chung, K.M.; Park, T.W.

2000-05-01

Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a {mu}-opioid receptor agonist) and {beta}-endorphin (an {epsilon}-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, {gamma}-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a {delta}-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of {gamma}-irradiation on the antinociception produced by i.c.v. injected morphine and {beta}-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co {gamma}-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or {beta}-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by {beta}-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of {mu}- and {epsilon}-opioid receptors to {gamma}-irradiation, in addition, support the hypothesis that morphine and {beta}-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)
Antinociceptive Properties of Ascorbic Acid: Evidence for the Mechanism of Action

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Zeraati

2014-09-01

Full Text Available Background Ascorbic acid is amongst important water-soluble vitamins and when used orally in high-doses it has been observed to relieve pain and reduce opioid use in patients. However no controlled trial has compared the antinociceptive effects of ascorbic acid with other analgesic groups on animal models, and investigated the involved mechanisms. Objectives In the present study, the antinociceptive effect of vitamin C on male mice was investigated and compared with morphine and diclofenac. Also, possible mechanisms were assayed. Materials and Methods Male albino mice were used in this study. Antinociception was measured using the writhing test, tail flick and formalin tests. Ascorbic acid was used in three doses (30, 150 and 300 mg/kg, IP and compared with the antinociceptive effects of 10 mg/kg of morphine as an opioid analgesic agent and 5-10 mg/kg of diclofenac as a nonsteroidal anti-inflammatory drug (NSAID analgesic agent.The antinociceptive effect of ascorbic acid (300 mg/kg was compared before and after treatment with naloxone (4 mg/kg, ondansetron (0.5 mg/kg, atropine (5 mg/kg and metoclopramide (1 mg/kg in the writhing test. Results Vitamin C caused dose-dependent antinociceptive effects in acetic acid writhing test (P < 0.05. It had no significant effect in the tail flick test. Meanwhile, vitamin C in high doses reduced pain in the second phase of the formalin test (P < 0.05. Morphine had higher nociceptive effects in comparison to ascorbic acid in the writhing test (P < 0.05. In the second phase of the formalin test the antinociceptive effects of vitamin C (300 mg/kg was not significantly different with morphine at dose of 10 mg/kg. There was not significant difference between vitamin C (300 mg/kg and diclofenac (10 mg/kg in the second phase of the formalin test. Metoclopramide and ondansetrone reduced the antinociceptive effects of vitamin C. Conclusions The results obtained from the acetic acid induced writhing test and second
Evaluation of antinociceptive effect of Petiveria alliacea (guiné in animals

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Thereza C. M. de Lima

1991-01-01

Full Text Available Petiveria alliacea (Phytolaccaceae is a bush widely distributed in South America including Brazil, where it is popularly known as "guiné", pipi", "tipi" or "erva-de-tipi". Brazilian folk medicine attributes to the hot water infusion of its roots or leaves the following pharmacologicalproperties: antipyretic, antispasmodic, abortifacient, antirrheumatic, diuretic, analgesic and sedative. The present study has evaluated the alleged effects of P. alliacea on central nervous system (CNS, particularly, the sedative and analgesic properties of root crude aqueous extract of this plant in mice and rats. This extract showed an antinociceptive effect in acetic acid - acetylcholine - and hypertonic saline - induced abdominal constrictions, but not in hot-plate and tail flick tests P. alliacea did not produce any CNS depressor effect. Thus its antinociceptive action in animals can be responsible by its poplar use as an analgesic.
Evaluation of antinociceptive effect of Petiveria alliacea (Guiné) in animals.

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de Lima, T C; Morato, G S; Takahashi, R N

1991-01-01

Petiveria alliacea (Phytolaccaceae) is a bush widely distributed in South America including Brazil, where it is popularly known as "guiné", "pipi", "tipi" or "erva-de-tipi". Brazilian folk medicine attributes to the hot water infusion of its roots or leaves the following pharmacological properties: antipyretic, antispasmodic, abortifacient, antirrheumatic, diuretic, analgesic and sedative. The present study has evaluated the alleged effects of P. alliacea on central nervous system (CNS), particularly, the sedative and analgesic properties of root crude aqueous extract of this plant in mice and rats. This extract showed an antinociceptive effect in acetic acid--acetylcholine--and hypertonic saline--induced abdominal constrictions, but not in hot-plate and tail flick tests. P. alliacea did not produce any CNS depressor effect. Thus its antinociceptive action in animals can be responsible by its popular use as an analgesic.
Melatonin in antinociception: its therapeutic applications.

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Srinivasan, Venkatramanujam; Lauterbach, Edward C; Ho, Khek Yu; Acuña-Castroviejo, Dario; Zakaria, Rahimah; Brzezinski, Amnon

2012-06-01

The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord and supraspinal levels. The mechanism of antinociceptive actions of melatonin involves opioid, benzodiazepine, α(1)- and α(2)-adrenergic, serotonergic and cholinergic receptors. Most importantly however, the involvement of MT(1)/MT(2) melatonergic receptors in the spinal cord has been well documented as an antinociceptive mechanism in a number of animal models of pain perception. Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT(1)/MT(2) melatonin receptors, plays an important role in the pathophysiological mechanism of pain.
Antinociceptive effects of methadone combined with detomidine or acepromazine in horses.

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Lopes, C; Luna, S P L; Rosa, A C; Quarterone, C; Crosignani, N; Taylor, P M; Pantoja, J C; Puoli, J N P

2016-09-01

To investigate two protocols to provide antinociception in horses. To evaluate the antinociceptive effects of intravenous methadone combined with detomidine or acepromazine in adult horses. Randomised, blinded, crossover study. Mechanical, thermal and electrical stimuli were applied to the dorsal left and right metacarpus and coronary band of the left thoracic limb, respectively. A thermal stimulus was applied caudal to the withers. The horses were treated with saline (C), a combination of methadone (0.2 mg/kg bwt) and detomidine (10 μg/kg bwt) (MD) or methadone (0.2 mg/kg bwt) and acepromazine (0.05 mg/kg bwt) (MA) at 1 week intervals. Nociceptive thresholds were measured before and at 15 min intervals until 150 min after treatment. Wilcoxon rank-sum and Wilcoxon signed rank tests were used to compare data between groups at each time point and over time within each group, followed by the Bonferroni method to adjust the P value. The mechanical stimulus was the most sensitive test to differentiate the antinociceptive effects of the treatments. Mechanical thresholds were greater after MD than MA between 15 and 30 min and with both MD and MA these thresholds were greater than C from 15 to 60 min. Electrical and thermal limb thresholds were greater after MD than C at 15 and 45 min and at 15, 30, 45, 75 and 105 min, respectively. Thermal limb thresholds were greater with MA than C at 30 min. Thoracic thermal threshold in MD and MA were higher than C at 45, 75, 90 and 120 min and from 30 to 75 min, respectively. Methadone and acepromazine produced less pronounced mechanical antinociception than MD. © 2015 EVJ Ltd.
The Antinociceptive Effects of Iranian Cobra Snake Venom using Formalin Test

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Zahra Hadi Chegeni

2015-06-01

Full Text Available Abstract Background: There have been numerous reports of snake venoms being employed as analgesics in attempts to relieve severe pain associated with cancer, immune dysfunction and viral infections. This study investigates the antinociceptive effects of iranian cobra snake venom (Naja naja oxiana in comparison with morphine and lidocain on laboratorial femal mice. Materials and Methods: This study has been done on 48 NMRI female mice of 18-20 g in weight. Antinociceptive activeity of snake venom was evaluated by formalin test. In this test, the animals were divided into 6 groups (each group consisting of 8 mice: Sham, positive Control (receiving morphine at dose of 5 mg/kg, and receiving lidocain at dose of 20 mg/kg, and experimental groups receiving venom at doses of 1, 3 and 4/5 µg/mice. In all groups, the formalin test was recorded for 60 min after administration of venom and drugs in mice. Data were analyzed using one-way ANOVA and Tukey test. Results: The results showed that the venom of Naja naja oxiana decreased nociception meaningfully in both acute and chronic phases. We also showed that this venom revealed even a better analgesic activity in comparison with morphine and lidocain. Conclusion: This study showed that the antinociceptive effect of the venom was mediated through central nervous system and peripheral mechanisms. Although details of the mechanism remain unclear, and further studies should be considered to demonstrate its therapeutic effects.
Adrenergic Component of Nicotine Antinociception in Rats | Ibironke ...

African Journals Online (AJOL)

African Journal of Biomedical Research ... Abstract. It has been widely established that nicotine , the active pharmacological agent in tobacco has antinociceptive effects , but the mechanism of this activity is yet to be fully ... These findings suggest the involvement of the adrenergic system in nicotine induced antinociception .
The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

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Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

2005-08-03

To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.
Libidibia ferrea mature seeds promote antinociceptive effect by peripheral and central pathway: possible involvement of opioid and cholinergic receptors.

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Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

2014-01-01

Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.
Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

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Luis Armando Sawada

2014-01-01

Full Text Available Libidibia ferrea (LF is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF, partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg, naloxone (5 mg/kg in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.
Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

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Hurt, Julie K; Coleman, Jennifer L; Fitzpatrick, Brendan J; Taylor-Blake, Bonnie; Bridges, Arlene S; Vihko, Pirkko; Zylka, Mark J

2012-01-01

Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.
Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

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Julie K Hurt

Full Text Available Thiamine (Vitamin B1 is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP can dephosphorylate BT in vitro, in dorsal root ganglia (DRG neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT then decomposes to O-benzoylthiamine (O-BT and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/- mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.
Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

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Abe, Kenji; Ishida, Kota; Kato, Masatoshi; Shigenaga, Toshiro; Taguchi, Kyoji; Miyatake, Tadashi

2002-11-01

To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests. Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine. These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.
Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test.

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Ortiz, Mario I

2012-01-02

Recent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and phenformin. Therefore, this work was undertaken to determine whether glibenclamide and glipizide and the biguanides metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. Diclofenac and indomethacin were administered locally in the formalin-injured rat paw, and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K(+) channels or biguanides-induced mechanisms, the effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. Local peripheral injections of diclofenac (50-200 μg/paw) and indomethacin (200-800 μg/paw) produced a dose-dependent antinociception during the second phase of the test. Local pretreatment with glibenclamide, glipizide, metformin and phenformin blocked the diclofenac-induced antinociception. On the other hand, the pretreatment with glibenclamide and glipizide did not prevent the local antinociception produced by indomethacin. Nonetheless, metformin and phenformin reversed the local antinociception induced by indomethacin. Data suggest that diclofenac could activate the K(+) channels and biguanides-dependent mechanisms to produce its peripheral antinociceptive effects in the formalin test. Likewise, a biguanides-dependent mechanism could be activated by indomethacin consecutively to generate its peripheral antinociceptive effect. Copyright © 2011 Elsevier Inc. All rights reserved.
Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

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Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng

2006-09-01

Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.
Antinociception induced by atorvastatin in different pain models.

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Garcia, G G; Miranda, H F; Noriega, V; Sierralta, F; Olavarría, L; Zepeda, R J; Prieto, J C

2011-11-01

Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models. Copyright © 2011 Elsevier Inc. All rights reserved.
Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide.

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Souto-Maior, Flávia Negromonte; Fonsêca, Diogo Vilar da; Salgado, Paula Regina Rodrigues; Monte, Lucas de Oliveira; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega

2017-12-01

Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance. To evaluate OXL's acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice. OXL (50, 100 and 150 mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30 min before for pharmacological tests. OXL showed an LD 50 of ∼721 (681-765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal's motor coordination. OXL significantly reduced (p monoterpene may lead to the development of a new molecule with even higher potency and selectivity.

Antinociceptive and anti-inflammatory effects of Lantana camara L. extract in mice

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T.S.C. SILVA

2015-06-01

Full Text Available ABSTRACT:he Lantana camara L. belongs to the family Verbenaceae, which contains several active compounds in leaves and roots and which are reported to have medicinal and insecticidal properties. Studies of plants within the same family show the existence of anti-inflammatory activity in paw edema induced by carrageenan, serotonin and histamine and analgesic activity in the acetic acid writhing and tail-flick tests. The present study investigated whether the L. camara extract (ACE also exerts these effects. The ACE toxicity was studied in male mice, and the percentage of mortality recorded 7 days after treatment was assessed. The ACE was evaluated as an antinociceptive agent in the hot plate, tail-flick and acetic acid writhing tests at a nontoxic dose of 1.0 g/Kg. The results showed that 1.5 g/Kg of ACE was not able to cause death, and doses of 3.0 and 4.0 g/Kg caused 50% and 60% death, respectively, in male mice. In all of the antinociceptive tests, 1 g/Kg of ACE markedly reduced responses to pain. Our findings suggest that ACE may have active anti-inflammatory and antinociceptive properties in much smaller doses than toxic.
Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats

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Akbari, Esmaeil; Mirzaei, Ebrahim; Shahabi Majd, Naghi

2013-01-01

This study investigates the effectiveness of the antinociceptive effects of diclofenac, an NSAID, on the nociceptive behavior of morphine-treated rats on formalin test. Rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. The antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain. Diclofenac potentiated pain suppression in morphine-de...
Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice.

Science.gov (United States)

Goh, Jun Zheng; Tang, Sook Nai; Chiong, Hoe Siong; Yong, Yoke Keong; Zuraini, Ahmad; Hakim, Muhammad Nazrul

2015-01-01

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall-Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall-Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.
Antinociceptive Effect of Ondansetron in Albino Mice Using Acetic Acid Induced Writhing Model

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Abhay Purohit

2016-10-01

Full Text Available Background: Pain is an unpleasant sensory and emotional experience. Pain is a protective mechanism. Pain occurs whenever any tissues are being damaged, and it causes the individual to react and to remove the pain stimulus. Aim and Objectives: To evaluate the antinociceptive effect of ondansetron in comparison with the standard diclofenac. Material and Methods: The antinociceptive effect was tested by using the acetic acid induced writhing model in Swiss Albino mice. Animals were divided into 4 groups of 6 animals each. Animals were received distilled water (control, diclofenac (standard, ondansetron 0.5mg/kg (test I and ondansetron 1mg/kg (test II. After 30 minutes of drug administration, 0.1 ml of 1% acetic acid was injected. Mice were placed individually into glass beakers and five minutes were allowed to elapse. They were then observed for a period of ten minutes and the numbers of writhes were recorded in each animal. The results were expressed as mean ± SEM. One way ANOVA with post-test was used for statistical calculation. Results: The numbers of writhes were 1.33±0.494 for diclofenac; 6.33±1.872 and 9.33±1.706 for ondansetron 0.5 and 1mg/kg respectively. Conclusion: Ondansetron demonstrated statistical significant antinociceptive activity at both doses (0.5mg/kg and 1mg/kg and statistically similar effect as diclofenac
Phytohormone abscisic acid elicits antinociceptive effects in rats through the activation of opioid and peroxisome proliferator-activated receptors β/δ.

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Mollashahi, Mahtab; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed

2018-08-05

The phytohormone abscisic acid exists in animal tissues particularly in the brain. However, its neurophysiological effects have not yet been fully clarified. This study was designed to evaluate the possible antinociceptive effects of abscisic acid on animal models of pain and determine its possible signaling mechanism. Tail-flick, hot-plate and formalin tests were used to assess the nociceptive threshold. All experiments were carried out on male Wistar rats. To determine the role of Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and opioid receptors on the induction of abscisic acid antinociception, specific antagonists were injected 15 min before abscisic acid. The data showed that abscisic acid (5, 10 and 15 µg/rat, i.c.v.) significantly decreased pain responses in formalin test. In addition, it could also produce dose-dependent antinociceptive effect in tail-flick and hot-plate tests. Administration of PPARβ/δ antagonist (GSK0660, 80 nM, i.c.v.) significantly attenuated the antinociceptive effect of abscisic acid in all tests. The antinociceptive effects of abscisic acid were completely inhibited by naloxone (6 µg, i.c.v.) during the time course of tail-flick and hot-plate tests. The results indicated that the central injection of abscisic acid has potent pain-relieving property which is mediated partly via the PPAR β/δ and opioid signaling. Copyright © 2018 Elsevier B.V. All rights reserved.
Antinociceptive effect on mice of the hydroalcoholic fraction and (- epicatechin obtained from Combretum leprosum Mart & Eich

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L.S. Lopes

2010-12-01

Full Text Available Previous studies on Combretum leprosum, a tree growing in the Northeastern states of Brazil, have shown antinociceptive effects of the ethanol extract of its leaves and bark, but studies examining its constituents are rare. The objective of this study was to evaluate the antinociceptive effect of the hydroalcoholic fraction (HF of one of its constituents, the flavonoid (- epicatechin (EPI, administered orally to mice (20-30 g in models of chemical nociception, and the possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg and EPI (12.5 to 50 mg/kg were evaluated in models of abdominal writhing, glutamate, capsaicin, and formalin in animals pretreated with different antagonists: naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in the abdominal writhing test. To determine the role of nitric oxide, the animals were pretreated with L-arginine (600 mg/kg, ip in the glutamate test. The HF was effective (P < 0.05 in all protocols at different doses and EPI was effective in the abdominal writhing, capsaicin and glutamate tests (P < 0.05 at doses of 25 and 50 mg/kg. However, in the formalin test it was only effective in the second phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when HF was associated with yohimbine (0.15 mg/kg, ketanserine (0.03 mg/kg, and L-arginine (600 mg/kg, but not with the other antagonists. HF and EPI were effective in models of chemical nociception, with the suggested participation of the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect of HF.
Influence of oxcarbazepine on the antinociceptive action of morphine and metamizole in mice.

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Pakulska, Wanda; Czarnecka, Elzbieta

2009-01-01

Numerous methods of management applied in order to obtain higher therapeutic efficacy of drugs with minimum adverse effects include taking advantage of interactions taking place between individual agents. Analgesics are combined with drugs belonging to other therapeutic groups, including, more and more frequently, antiepileptic agents. The influence of oxcarbazepine (10 mg/kg) on the antinociceptive effect of morphine (10 mg/kg) and metamizole (500 mg/kg) was investigated in mice using the hot-plate and tail-flick tests. All drugs were injected intraperitoneally (i.p.). Oxcarbazepine was administered 30 min prior to the injection of analgesic drugs. The reactions to noxious stimuli were measured 30, 60 and 90 min after the administration of an analgesic. The study was further conducted for 10 days with repeated drug doses. Single administration of oxcarbazepine enhanced the antinociceptive effect of a single dose of morphine, and 10-day administration led to a decrease of morphine tolerance in the hot-plate test. Oxcarbazepine administered in a single dose did not affect significantly the antinociceptive effect of metamizole in either of the tests. Multiple administration of oxcarbazepine enhanced the antinociceptive effect of metamizole in the hot-plate test. Oxcarbazepine alone, administered in a single and repeated doses, demonstrated an antinociceptive effect, but only for the hot-plate test, which indicates involvement of supraspinal structures in antinociception.
Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone.

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Huang, Y; Brodda-Jansen, G; Lundeberg, T; Yu, L C

2000-08-04

The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.
Antinociceptive esters of N-methylanthranilic acid: Mechanism of action in heat-mediated pain.

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Pinheiro, Mariana Martins Gomes; Radulović, Niko S; Miltojević, Ana B; Boylan, Fabio; Dias Fernandes, Patrícia

2014-03-15

Recently, we identified a new natural antinociceptive alkaloid ternanthranin, isopropyl N-methylanthranilate (ISOAN), from the plant species Choisya ternata Kunth (Rutaceae). In this work we concentrated on the elucidation of its mechanism of action in comparison with two other esters of this acid (methyl (MAN) and propyl (PAN)). Mice orally pre-treated with ISOAN, MAN or PAN (at 0.3, 1 and 3mg/kg) were less sensitive to chemical or thermal stimuli in different nociception models (formalin-, capsaicin- and glutamate-induced licking response, tail flick and hot plate). All compounds (1 and 3mg/kg) showed significant activity in the peripheral nociception models, as well as a dose-dependent spinal antinociceptive effect in the tail flick model. We observed that glibenclamide was able to reverse the antinociceptive effect of ISOAN in the hot plate model suggesting the involvement of K(+)ATP channels. The antinociceptive effect of MAN and PAN may be related to adrenergic, nitrergic and serotoninergic pathways. In addition, the antinociception of PAN was reverted by naloxone implying that the opioid pathway participates in its activity. The cholinergic and cannabinoid systems were found not be involved in the onset of the antinociceptive effects of any of the esters. In conclusion, isopropyl, methyl and propyl N-methylanthranilates produced significant peripheral and central antinociception at doses lower than that of morphine, the classical opioid analgesic drug, without causing toxicity. Copyright © 2014 Elsevier B.V. All rights reserved.
Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats

DEFF Research Database (Denmark)

Kristensen, Sara Hestehave; Munro, Gordon; Brønnum Pedersen, Tina

2017-01-01

the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (Peffects were not as marked......Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice....... In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing...
Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in thermal injury

DEFF Research Database (Denmark)

Pedersen, J L; Møiniche, S; Kehlet, H

1994-01-01

We have studied the antinociceptive and anti-inflammatory effects of topical glucocorticoids in human thermal injury. The right and left legs of 12 healthy volunteers were allocated randomly to be treated with either 0.05% clobetasol propionate cream or placebo in a double-blind trial. Thermal...
Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats.

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Liévano-Reyes, Ricardo; Pérez-Méndez, Hermínia Ines; Solís-Oba, Aida; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

2016-06-01

Preclinical Research Drug combinations are routinely used in the treatment of pain. In drug associations, adjuvants such as caffeine, are employed with different non-steroidal anti-inflammatories drugs (NSAIDs), however, at present does not exist studies showing the effect of the combination of racemic flurbiprofen (rac-Flur) in association with caffeine. The objective of this work was to evaluate the combination of rac-Flur + caffeine oral in arthritic gout-type pain in rats. The antinociceptive effects of the rac-Flur alone and in combination with caffeine were analyzed on a pain-induced functional impairment model in rat. rac-Flur induced a dose-dependent antinociceptive effect and caffeine did not present any effect. The combination of rac-Flur and caffeine achieve a higher percentage of antinociceptive effect compared with the individual administration of rac-Flur. The dose-response curve (DRCs) shows that the combination of rac-Flur (31.6 mg/kg) + caffeine (17.8 mg/kg) exhibited the maximal antinociceptive efficacy (294.0 ± 21.2 area units), while rac-Flur alone (31.6 mg/kg) showed 207.2 ± 35.2 au, thus indicating an increase in efficacy (potentiation). Furthermore, the DRCs of the combinations presented a displacement to the left, indicating a change in the potency. Caffeine is able to increase the effect of rac-Flur in the arthritic gout-type pain in rats. Drug Dev Res 77 : 192-198, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Melatonin in Antinociception: Its Therapeutic Applications

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Srinivasan, Venkatramanujam; Lauterbach, Edward C; Ho, Khek Yu; Acuña-Castroviejo, Dario; Zakaria, Rahimah; Brzezinski, Amnon

2012-01-01

The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord a...
Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

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Goh JZ

2014-12-01

Full Text Available Jun Zheng Goh,1 Sook Nai Tang,1 Hoe Siong Chiong,1,2 Yoke Keong Yong,3 Ahmad Zuraini,1 Muhammad Nazrul Hakim1,4 1Department of Biomedical Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2InQpharm Group, Kuala Lumpur, Malaysia; 3Department of Human Anatomy, 4Halal Product Research Institute, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall–Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall–Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect
Antinociceptive Action of Isolated Mitragynine from Mitragyna Speciosa through Activation of Opioid Receptor System

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Mohamad Aris Mohd Moklas

2012-09-01

Full Text Available Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG, a major indole alkaloid found in Mitragyna speciosa (MS can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1 and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt. In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist, naloxone (non-selective opioid antagonist, naltrindole (δ-opioid antagonist naloxonazine (µ1-receptor antagonist and norbinaltorpimine (κ-opioid antagonist respectively, prior to administration of MG (35 mg/kg. The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.
The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the rat inflamed joint model.

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Mecs, Laszlo; Tuboly, Gabor; Nagy, Endre; Benedek, Gyorgy; Horvath, Gyongyi

2009-10-01

Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/20 microL) into the tibiotarsal joint of the right hind leg. The mechanical pain threshold was assessed by von Frey filaments (0.064-110 g). EM1 (30, 100, and 200 microg), KYNA (30, 100, 200, and 400 microg), and their combinations in a fixed-dose ratio (1:1) were injected into the inflamed joint, and the pain threshold was determined repeatedly for 75 min after the drug administrations. Neither EM1 nor KYNA administered to the inflamed joint influenced the pain threshold at the noninflamed side. Both ligands produced dose-dependent antihyperalgesia, and the highest doses caused a prolonged effect. EM1 had higher potency (30% effective dose [ED(30)] and 50% effective dose [ED(50)] values were 112 microg [confidence interval {CI}: 80-146] and 167 microg [CI: 135-220], respectively) compared with KYNA (ED(30) and ED(50) values were 204 microg [CI: 160-251] and 330 microg [CI: 280-407], respectively). The antinociceptive effect of EM1 was prevented by subcutaneous naltrexone pretreatment. The coadministration of EM1 with KYNA caused an enhanced and/or prolonged antinociceptive effect. The ED(30) and ED(50) values of the combination were 141 microg [CI: 83-182] and 231 microg [CI: 190-293], respectively, which did not differ significantly from the theoretically additive values (ED(30) and ED(50) values were 145 microg
TRPV1 in brain is involved in acetaminophen-induced antinociception.

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Christophe Mallet

2010-09-01

Full Text Available Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404 by fatty acid amide hydrolase (FAAH in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV(1 in vitro. Pharmacological activation of TRPV(1 in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV(1 in the brain contributes to the analgesic effect of acetaminophen.Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV(1 knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E(2 (PGE(2 and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV(1-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV(1 in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test.This study shows that TRPV(1 in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV(1 in the brain.
Antinociceptive activity of Inula britannica L. and patuletin: In vivo and possible mechanisms studies.

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Zarei, Mohammad; Mohammadi, Saeed; Komaki, Alireza

2018-06-12

Inula britannica L. is a predominant medicinal plant traditionally utilized in the treatments of arthritis and back pain in Iranian folk medicine. The purpose of this research was to evaluate the antinociceptive effects of Inula britannica L. flower essential oil (IBLEO) and one of its major constituents, Patuletin (Pn), in male mice. In this study, we used pain assessment tests including acetic acid-induced writhing, tail-flick (TF), formalin induced paw licking (FIPL) model, and glutamate-induced paw licking (GPL). For understanding the supposed antinociceptive mechanisms of IBLEO, opioid and L-arginine/NO/cGMP/ KATP pathways were examined. In the TF, writhing, GPL, and FIPL tests, a dosage of 100 mg/kg of IBLEO showed noteworthy antinociceptive effects in comparison with control (p L-arginine or sodium nitroprusside fundamentally potentiated the antinociception induced by IBLEO in phase II of the FIPL (p L-arginine/NO/cGMP/KATP pathway in IBLEO antinociceptive effects. Copyright © 2018 Elsevier B.V. All rights reserved.
Botulinum neurotoxin type-A when utilized in animals with trigeminal sensitization induced a antinociceptive effect

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Elcio J Piovesan

2016-06-01

Full Text Available ABSTRACT Purpose of the study was evaluate the possible antinociceptive effect of botulinum neurotoxin type-A (BoNT/A in an experimental model of trigeminal neuralgia. Method Neuropathic pain was induced by surgical constriction of the infraorbital nerve in rats. A control group underwent a sham procedure consisting of surgical exposure of the nerve. Subgroups of each group received either BoNT/A or isotonic saline solution. The clinical response was assessed with the -20°C test. Animals that underwent nerve constriction developed sensitization; the sham group did not. Results The sensitization was reversed by BoNT/A treatment evident 24 hours following application. Pronociceptive effect was observed in the sham group following BoNT/A. Conclusion BoNT/A has an antinociceptive effect in sensitized animals and a pronociceptive effect in non-sensitized animals.
Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

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Md. Josim Uddin; A. S. M. Ali Reza; Md. Abdullah-Al-Mamun; Mohammad S. H. Kabir; Mst. Samima Nasrin; Sharmin Akhter; Md. Saiful Islam Arman; Md. Atiar Rahman

2018-01-01

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental...

Comparison between oral and intra-articular antinociceptive effect of dexketoprofen and tramadol combination in monosodium iodoacetate-induced osteoarthritis in rats.

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Cialdai, Cecilia; Giuliani, Sandro; Valenti, Claudio; Tramontana, Manuela; Maggi, Carlo Alberto

2013-08-15

Dexketoprofen and tramadol, alone or in combination, were evaluated after oral or intra-articular administration on knee osteoarthritis nociception induced by intra-articular (i.ar.) monosodium iodoacetate (MIA, 1 mg/25 µl) in the rat right knee while the left knee received saline (25 µl). Seven days after MIA treatment, dexketoprofen, tramadol, their combination or the vehicle were administered. Nociception was evaluated as alteration in hind limb weight distribution with Incapacitance tester at different time-points after drug administration. Oral dexketoprofen (0.1-1 mg/kg) or tramadol (0.5-5 mg/kg) induced maximal antinociception at 1 and 5 mg/kg, respectively. Their combination dose-dependently increased the intensity and duration of antinociception, that was additive and lasted up to 3 days. Also the intra-articular administration of dexketoprofen or tramadol (10-100 µg/25 µl) inhibited MIA-induced nociception, and the combination of the lower doses (10 µg/25 µl) produced a long lasting more than additive antinociceptive effect indicating a synergistic interaction between the two drugs. This effect was significantly reduced by naloxone (10 μg/25 μl, i.ar.) co-administered with both compounds. The intra-articular administration of both drugs at 10 µg/25 µl in the contralateral control knee joint provoked a marked synergistic antinociceptive effect indicating significant systemic diffusion through synovial membrane. The oral or intra-articular combination of dexketoprofen and tramadol produced additive or synergistic antinociceptive effects, respectively, in the model of MIA-induced osteoarthritis in rats, that might allow to obtain therapeutic advantages with lower side effects. © 2013 Elsevier B.V. All rights reserved.
Antinociceptive activity of Sempervivum tectorum L. extract in rats.

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Kekesi, Gabriella; Dobos, Ildiko; Benedek, György; Horvath, Gyöngyi

2003-11-01

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract. Copyright 2003 John Wiley & Sons, Ltd.
Antinociceptive effect of extracts of Marrubium astracanicum Jacq. aerial parts

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Niloofar Kahkeshani

2017-01-01

Full Text Available Objective: The genus Marrubium is used for treatment of joint pain, gout, stomach-ache and colic in Iranian Traditional Medicine. Marrubium astracanicum Jacq. (M. astracanicum is a native species in the flora of Iran. The aim of this study was to evaluate the antinociceptive properties of various extracts of aerial parts of M. astracanicum.Materials and Methods: Antinociceptive activities of total hydroalcoholic extract (THE and its n-hexane (non-polar and residual partition (polar fractions were analyzed using formalin test in mice. Morphine (5 mg/kg and normal saline were used as positive and negative controls, respectively.Results: Intraperitoneal administration of THE (50, 100 and 200 mg/kg, non-polar fraction (200 mg/kg and polar fraction (100 and 200 mg/kg, 30 min before formalin injection, caused significant analgesic activity in acute phase (0-5 min after formalin injection of formalin test (p0.05 in comparison with morphine. In chronic phase (15–60 min after formalin injection, non-polar and polar fractions (50, 100 and 200 mg/kg showed significant analgesic activity (p0.05 in comparison with morphine.Conclusion: Different extracts of M. astracanicum demonstrated antinociceptive activity that support the traditional usage of Marrubium genus for the treatment of arthritis, gout and other inflammatory diseases.
Assessment of anti-nociceptive efficacy of costus speciosus rhizome in swiss albino mice.

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Bhattacharya, Sanjib; Nagaich, Upendra

2010-01-01

Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE) in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA) significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE) produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE) showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.
Assessment of anti-nociceptive efficacy of Costus Speciosus rhizome in swiss albino mice

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Sanjib Bhattacharya

2010-01-01

Full Text Available Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.
Antinociception induced by chronic glucocorticoid treatment is correlated to local modulation of spinal neurotransmitter content

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Almeida Armando

2009-07-01

Full Text Available Abstract Background While acute effects of stress on pain are well described, those produced by chronic stress are still a matter of dispute. Previously we demonstrated that chronic unpredictable stress results in antinociception in the tail-flick test, an effect that is mediated by increased levels of corticosteroids. In the present study, we evaluated nociception in rats after chronic treatment with corticosterone (CORT and dexamethasone (DEX in order to discriminate the role of each type of corticosteroid receptors in antinociception. Results Both experimental groups exhibited a pronounced antinociceptive effect after three weeks of treatment when compared to controls (CONT; however, at four weeks the pain threshold in CORT-treated animals returned to basal levels whereas in DEX-treated rats antinociception was maintained. In order to assess if these differences are associated with altered expression of neuropeptides involved in nociceptive transmission we evaluated the density of substance P (SP, calcitonin gene-related peptide (CGRP, somatostatin (SS and B2-γ-aminobutiric acid receptors (GABAB2 expression in the spinal dorsal horn using light density measurements and stereological techniques. After three weeks of treatment the expression of CGRP in the superficial dorsal horn was significantly decreased in both CORT and DEX groups, while GABAB2 was significantly increased; the levels of SP for both experimental groups remained unchanged at this point. At 4 weeks, CGRP and SP are reduced in DEX-treated animals and GABAB2 unchanged, but all changes were restored to CONT levels in CORT-treated animals. The expression of SS remained unaltered throughout the experimental period. Conclusion These data indicate that corticosteroids modulate nociception since chronic corticosteroid treatment alters the expression of neuropeptides involved in nociceptive transmission at the spinal cord level. As previously observed in some supraspinal areas, the
Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice.

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Shajib, Md Shafiullah; Rashid, Ridwan B; Ming, Long C; Islam, Shanta; Sarker, Md Moklesur R; Nahar, Lutfun; Sarker, Satyajit D; Datta, Bidyut K; Rashid, Mohammad A

2018-01-01

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia , an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone ( 1 ), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) ( 2 ), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone ( 3 ), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone ( 4 ), isolated and identified from N. plumbaginifolia . Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1 , 3 , and 4 (12.5-25 mg/kg b.w.) exhibited dose-dependent and significant ( p Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents.
Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

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Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.
Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

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Laura S Stone

Full Text Available Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs. Analgesics acting at α2ARs and opioid receptors (ORs frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C. Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic
Anti-inflammatory, and antinociceptive effects of Campomanesia adamantium microencapsulated pulp

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Danieli Z. Viscardi

Full Text Available ABSTRACT Guavira fruits have antimicrobial, antioxidant, antinociceptive, and anti-inflammatory activities. Spray drying has been widely used in the food industry presenting good retention in bioactive compounds used to transform the pulp/fruit juice into powder form. Therefore, the present study has evaluated the anti-inflammatory and antinociceptive activities of the microencapsulated pulp of Campomanesia adamantium (Cambess. O.Berg, Myrtaceae, by spray drying. Different groups of mice were treated with the doses of 100 and 300 mg/kg of microencapsulated "guavira" pulp and inflammatory parameters were assessed in a carrageenan paw edema-model and leukocyte migration with pleurisy model, while the antinociceptive activity was assessed using the formalin method and CFA-induced hyperalgesia model. A significant reduction in leukocyte migration and in paw edema was observed in rodents in all time after carrageenan injection for both doses of microencapsulated pulp of C. adamantium when compared with control group. Microencapsulated pulp of C. adamantium also reduced licking time at the first (nociceptive and second (inflammatory phases in the formalin model. In CFA-induced cold and mechanical hyperalgesia, depressive behavior, and knee edema, all parameters analyzed were significantly inhibited by microencapsulated pulp of C. adamantium. Microencapsulation by spray drying proved to be a technique that promotes bioavailability and the preservation of bioactive components in guavira pulp.
Antinociceptive principle from Curcuma aeruginosa

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Hossain, Chowdhury Faiz; Al-Amin, Mohammad; Sayem, Abu Sadat Md.; Siragee, Ismail Hossain; Tunan, Asif Mahmud; Hassan, Fahima; Kabir, Md. Mohiuddin; Sultana, Gazi Nurun Nahar

2015-01-01

Background The rhizome of Curcuma aeruginosa Roxb (Zingiberaceae) has been used as a traditional folk medicine for the treatment of rheumatic disorders in Bangladesh. The aim of the current study was the bioassay-guided isolation and purification of an antinociceptive principle from the methanol extract of C. aeruginosa rhizomes. Methods The antinociceptive activity was determined using acetic acid induced writhing and formalin induced licking in the Swiss albino mice to investigate central a...
Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheral β-Adrenoceptors

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Suk-Yun Kang

2013-01-01

Full Text Available The injection of diluted bee venom (DBV into an acupoint has been used traditionally in eastern medicine to treat a variety of inflammatory chronic pain conditions. We have previously shown that DBV had a potent antinociceptive efficacy in several rodent pain models. However, the peripheral mechanisms underlying DBV-induced antinociception remain unclear. The present study was designed to investigate the role of peripheral epinephrine on the DBV-induced antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly enhanced the antinociceptive effect of DBV during the late phase of the formalin test, while chemical sympathectomy had no effect. Intraperitoneal injection of epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced antinociceptive effect. Moreover, injection of a phenylethanolamine N-methyltransferase (PNMT inhibitor enhanced the DBV-induced antinociceptive effect. Administration of nonselective β-adrenergic antagonists also significantly potentiated this DBV-induced antinociception, in a manner similar to adrenalectomy. These results demonstrate that the antinociceptive effect of DBV treatment can be significantly enhanced by modulation of adrenal medulla-derived epinephrine and this effect is mediated by peripheral β-adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of peripheral β-adrenoceptors could be a potentially novel strategy for the management of inflammatory pain.
Anti-inflammatory and Antinociceptive Effects of the Alcoholic Extract ...

African Journals Online (AJOL)

The alcoholic extract of Polygala arvensis (family Polygalaceae) was screened for antinociceptive and anti-inflammatory activities in experimental animals. The extract was administered for three consecutive days. Following an oral dose of 25 - 100 mg/kg, the extract exhibited graded dose response equivalent to 16.24% ...
Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

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Xiao Li

2014-07-01

Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.
Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds

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Carolina Carvalho Guilhon

2015-01-01

Full Text Available Pereskia bleo (Kunth DC. (Cactaceae is a plant commonly used in popular medicine in Malaysia. In this work, we evaluate the antinociceptive effect of P. bleo leaf extracts and isolated compounds in central antinociceptive model. Ethanol extract (E, hexane (H, ethyl acetate (EA, or butanol (B fractions (30, 50, or 100 mg/kg, p.o., sitosterol (from hexane and vitexin (from ethyl acetate, were administered to mice. Antinociceptive effect was evaluated in the hot plate and capsaicin- or glutamate-induced licking models. Morphine (1 mg/kg, p.o. was used as reference drug. Naloxone (1 mg/kg, i.p., atropine (1 mg/kg, i.p., and L-nitro arginine methyl ester (L-NAME, 3 mg/kg, i.p. were administered 30 min earlier (100 mg/kg, p.o. in order to evaluate the mechanism of the antinociceptive action. Higher dose of B developed an effect significantly superior to morphine-treated group. Naloxone prevented the antinociceptive effect of all fractions. L-NAME demonstrated effect against E, EA, and B. In all fractions, sitosterol and vitexin reduced the licking time after capsaicin injection. Glutamate-induced licking response was blocked by H, EA, and B. Our results indicate that Pereskia bleo fractions, sitosterol and vitexin, possessed a central antinociceptive effect. Part of this effect is mediated by opioid receptors and nitrergic pathway.
The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

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Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

2010-02-01

The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.
Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

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Jokinen, Viljami; Lilius, Tuomas; Laitila, Jouko; Niemi, Mikko; Kambur, Oleg; Kalso, Eija; Rauhala, Pekka

2017-01-01

Spironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co-administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)- and morphine (3 mg/kg, s.c.)-induced antinociception using tail-flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice.

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Fialho, Maria Fernanda Pessano; Brusco, Indiara; da Silva Brum, Evelyne; Piana, Mariana; Boligon, Aline Augusti; Trevisan, Gabriela; Oliveira, Sara Marchesan

2017-08-17

Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and β-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition ( I max ) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses.

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Gozalo-Marcilla, Miguel; Luna, Stelio Pl; Crosignani, Nadia; Filho, José Np Puoli; Possebon, Fábio S; Pelligand, Ludovic; Taylor, Polly M

2017-09-01

To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects. Randomized, placebo-controlled, blinded, crossover. A group of eight adult healthy horses aged (mean ± standard deviation) 7 ± 2 years and 372 ± 27 kg. A total of six treatments were administered IV: saline (SAL); detomidine (5 μg kg -1 ; DET); methadone (0.2 mg kg -1 ; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD) μg kg -1 ]. Thermal, mechanical and electrical nociceptive thresholds were measured, and sedation, head height above ground (HHAG), cardiopulmonary variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90, 120 and 180 minutes. Normal data were analyzed by mixed-model analysis of variance and non-normal by Kruskal-Wallis (p detomidine (MMD, MHD) were increased above baseline to a greater degree and for longer duration (MMD: 15-30 minutes, MHD: 30-60 minutes) than in horses administered low dose with methadone or detomidine alone (MLD, DET: 5-15 minutes). No increases in nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No significant sedation was observed in SAL, MET or MLD. Intestinal motility was reduced for 75 minutes in MHD and for 30 minutes in all other treatments. Methadone (0.2 mg kg -1 ) potentiated the antinociception produced by detomidine (5 μg kg -1 ), with minimal sedative effects. Detomidine (5 μg kg -1 ) with methadone (0.2 mg kg -1 ) produced antinociception without the adverse effects of higher doses of detomidine. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models.

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Hajhashemi, Valiollah; Klooshani, Vahid

2013-01-01

This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects. The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%. The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract.

Anti-nociceptive activity of Pereskia bleo Kunth. (Cactaceae) leaves extracts.

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Abdul-Wahab, Ikarastika Rahayu; Guilhon, Carolina Carvalho; Fernandes, Patricia Dias; Boylan, Fabio

2012-12-18

Local communities in Malaysia consume Pereskia bleo Kunth. (Cactaceae) leaves as raw vegetables or as a concoction and drink as a tea to treat diabetes, hypertension, rheumatism, cancer-related diseases, inflammation, gastric pain, ulcers, and for revitalizing the body. To evaluate anti-nociceptive activity of the extracts and vitexin, isolated for the first time in this species, in two analgesic models; formalin-induced licking and acetic acid-induced abdominal writhing. Three and a half kilos of P. bleo leaves were extracted using Soxhlet apparatus with ethanol for 72 h. The crude ethanol extract was treated with activated charcoal overnight and subjected to a liquid-liquid partition yielding hexane, dichloromethane, ethyl acetate and butanol extracts. All extracts, including the crude ethanol and vitexin isolated from the ethyl acetate partition were tested for peripheral anti-nociceptive activity using formalin test and acetic acid-induced abdominal writhing, besides having their acute toxicity assays performed. The phytochemical analyses resulted in the isolation of vitexin (1), β-sitosterol glucoside (2) and β-sitosterol (3) isolated from the ethyl acetate, dichloromethane and hexane extracts, respectively. This is the first time vitexin and β-sitosterol glucoside are isolated from this species. The anti-nociceptive activities for all extracts were only moderate. Vitexin, which was isolated from the ethyl acetate extract did not show any activity in all models tested when used alone at the same concentration as it appears in the extract. This study showed that all the extracts possess moderate anti-nociceptive activity. Vitexin is not the compound responsible for the anti-nociceptive effect in the ethyl acetate extract. Further investigations are needed to identify the compound(s) that might be responsible for the anti-nociceptive activity in this plant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Diabetes-causing gene, kruppel-like factor 11, modulates the antinociceptive response of chronic ethanol intake.

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Ou, Xiao-Ming; Udemgba, Chinelo; Wang, Niping; Dai, Xiaoli; Lomberk, Gwen; Seo, Seungmae; Urrutia, Raul; Wang, Junming; Duncan, Jeremy; Harris, Sharonda; Fairbanks, Carolyn A; Zhang, Xiao

2014-02-01

Alcohol (EtOH [ethanol]) is an antinociceptive agent, working in part, by reducing sensitivity to painful stimuli. The transcription factor Kruppel-like factor 11 (KLF11), a human diabetes-causing gene that also regulates the neurotransmitter metabolic enzymes monoamine oxidase (MAO), has recently been identified as an EtOH-inducible gene. However, its role in antinociception remains unknown. Consequently, we investigated the function of KLF11 in chronic EtOH-induced antinociception using a genetically engineered knockout mouse model. Wild-type (Klf11(+/+) ) and KLF11 knockout (Klf11(-/-) ) mice were fed a liquid diet containing EtOH for 28 days with increasing amounts of EtOH from 0% up to a final concentration of 6.4%, representing a final diet containing 36% of calories primarily from EtOH. Control mice from both genotypes were fed liquid diet without EtOH for 28 days. The EtOH-induced antinociceptive effect was determined using the tail-flick test before and after EtOH exposure (on day 29). In addition, the enzyme activity and mRNA levels of MAO A and MAO B were measured by real-time RT-PCR and enzyme assays, respectively. EtOH produced an antinociceptive response to thermal pain in Klf11(+/+) mice, as expected. In contrast, deletion of KLF11 in the Klf11(-/-) mice abolished the EtOH-induced antinociceptive effect. The mRNA and protein levels of KLF11 were significantly increased in the brain prefrontal cortex of Klf11(+/+) mice exposed to EtOH compared with control Klf11(+/+) mice. Furthermore, MAO enzyme activities were affected differently in Klf11 wild-type versus Klf11 knockout mice exposed to chronic EtOH. Chronic EtOH intake significantly increased MAO B activity in Klf11(+/+) mice. The data show KLF11 modulation of EtOH-induced antinociception. The KLF11-targeted MAO B enzyme may contribute more significantly to EtOH-induced antinociception. Thus, this study revealed a new role for the KLF11 gene in the mechanisms underlying the antinociceptive
NSAID Antinociception Measured in a Chemical and a Thermal Assay in Mice

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HF Miranda

2001-01-01

Full Text Available The antinociceptive activity of several nonsteroidal anti-inflammatory drugs (NSAIDs that were administered either intraperitoneally or intrathecally was assessed in mice by two algesiometric tests. The first was the writhing test, which assessed the abdominal constrictions that were induced by intraperitoneal acetic acid (a chemical test, and the second was the tail flick test, which measured pain responses to heat stimuli. The corresponding effective doses and their relative potencies were compared because these tests use different nociceptive stimuli with different transmission pathways. The intraperitoneal and intrathecal dose-response curves for the antinociception induced by every NSAID that was tested were parallel in the writhing test. In the tail flick test, however, only the intraperitoneal and intrathecal dose-response curves for ketoprofen, piroxicam, naproxen, nimesulide, paracetamol and diclofenac were parallel. The results obtained in this study confirm that NSAIDs possess different abilities to induce inhibition of cyclooxygenase, and they can be indirectly assessed by their different antinociceptive activities, depending on the algesiometric assays that are used. The antinociception of most NSAIDs might involve central mechanisms. The findings demonstrate the increasing importance of the spinal cord in processing and modulating nociceptive input, because intrathecal administration of NSAIDs is always more effective (in terms of potency than systemic administration; thus, the antinociceptive efficacy of NSAIDs strongly depends on the algesiometric assay that is used and on the type of the nociceptive stimulus to which the test subject is exposed.
Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testing in normal and monoarthritic rats.

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Pelissier, Teresa; Infante, Claudio; Constandil, Luis; Espinosa, Jeannette; Lapeyra, Carolina De; Hernández, Alejandro

2008-01-01

We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the antinociceptive effect of intrathecal administration of the drugs alone or combined was evaluated by using the intraplantar capsaicin and the paw pressure tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater dose-dependent antinociception in the capsaicin than in the paw pressure test. Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.
Anti-nociceptive and anti-hyperprolactinemia activities of Fructus Viticis and its effective fractions and chemical constituents.

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Hu, Y; Xin, H-L; Zhang, Q-Y; Zheng, H-C; Rahman, K; Qin, L-P

2007-10-01

Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).
Antinociceptive and anti-inflammatory activities of the methanol ...

African Journals Online (AJOL)

This study was aimed at screening the methanol tuber extract of Chlorophytum alismifolium for antinociceptive and anti-inflammatory activities using experimental animal models. The antinociceptive activity was tested using acetic acid-induced writhing response in Swiss albino mice and formalininduced pain in Wistar rats, ...
"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

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Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

2017-10-01

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.
Enhanced inhibitory synaptic transmission in the spinal dorsal horn mediates antinociceptive effects of TC-2559

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2011-01-01

Background TC-2559 is a selective α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist and α4β2 nAChR activation has been related to antinociception. The aim of this study is to investigate the analgesic effect of TC-2559 and its underlying spinal mechanisms. Results 1) In vivo bioavailability study: TC-2559 (3 mg/kg) had high absorption rate in rats with maximal total brain concentration reached over 4.6 μM within first 15 min after administration and eliminated rapidly with brain half life of about 20 min after injection. 2) In vivo behavioral experiments: TC-2559 exerts dose dependent antinociceptive effects in both formalin test in mice and chronic constriction injury (CCI) model in rats by activation of α4β2 nAChRs; 3) Whole-cell patch-clamp studies in the superficial dorsal horn neurons of the spinal cord slices: perfusion of TC-2559 (2 μM) significantly increased the frequency, but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). The enhancement of sIPSCs was blocked by pre-application of DHβE (2 μM), a selective α4β2 nicotinic receptor antagonist. Neither the frequency nor the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of spinal dorsal horn neurons were affected by TC-2559. Conclusions Enhancement of inhibitory synaptic transmission in the spinal dorsal horn via activation of α4β2 nAChRs may be one of the mechanisms of the antinociceptive effects of TC-2559 on pathological pain models. It provides further evidence to support the notion that selective α4β2 subtype nAChR agonist may be developed as new analgesic drug for the treatment of neuropathic pain. PMID:21816108
Anti-Inflammatory and Antinociceptive Activities of Untreated, Germinated, and Fermented Mung Bean Aqueous Extract

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Norlaily Mohd Ali

2014-01-01

Full Text Available Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB, germinated mung bean (GMB, and fermented mung bean (FMB was performed on both in vitro (inhibition of inflammatory mediator, nitric oxide(NO and in vivo (inhibition of ear oedema and reduction of response to pain stimulus studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner. In vitro results showed that GMB and FMB were potent inflammatory mediator (NO inhibitors at both 2.5 and 5 mg/mL. Further in vivo studies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and 1000 mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects.
Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor.

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Yu, Xuan; Wang, Xin-Pei; Yan, Xiao-Jin; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; Guo, Yue-Ying; Du, Li-Jun

2017-08-09

To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels. The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confifirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (Peffect of PA. A decrease in the intracellular calcium level (Peffect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.
The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism

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Nushrat Sharmin Ani

2016-01-01

Full Text Available Murraya koenigii L. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant’s leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract of M. koenigii (MEMK leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly (p<0.01 inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly (p<0.01 suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker at 10 mg/kg significantly (p<0.05 reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects of M. koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine.
Antinociceptive activity of Buddleja globosa (matico) in several models of pain.

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Backhouse, Nadine; Delporte, Carla; Apablaza, Cecia; Farías, Mariela; Goïty, León; Arrau, Sylvia; Negrete, Rosa; Castro, Consuelo; Miranda, Hugo

2008-09-02

Leaf extracts of Buddleja globosa (Buddlejaceae) are used in Chilean folk medicine for wound healing. The anti-inflammatory (topic and per os), analgesic (per os) effects and the antioxidant activity of Buddleja globosa were for the first time reported by us. Assess the antinociceptive activity of the methanol sequential and global extracts using complementary chemical and thermal models of pain, characterize pharmacologically the antinociception induced, evaluate seasonal influence to support Buddleja globosa medicinal use. Global methanol, sequential methanol and ethanol (leaves collected in autumn and summer) extracts were evaluated for oral and topic analgesia in tail flick, formalin and writhing models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and writhing. Ibuprofen was used as reference. For characterization of induced antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine, prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as antagonists and inhibitors drugs. Seasonal influence was observed since autumn extract resulted less active. Extracts showed a dose-dependent antinociceptive activity in all assays, the highest effects were obtained for the formalin and writhing test. Verbascoside was more active than ibuprofen in the writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to ibuprofen. Luteolin 7-O-glucoside was slightly more active in the tail flick test and nearly half active than verbascoside in the writhing assay. Effectiveness was higher for the sequential than for global alcoholic extracts, and can be increased by selective blocking of opioid receptors. Global methanol extract seems modulated only by naltrexone. Analgesic effect of Buddleja globosa is here demonstrated validating its use in traditional medicine. Season influence is important to be considered.
From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

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Schreiber, Shaul; Pick, Chaim G

2006-08-01

Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.
The novel δ opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions.

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Saitoh, Akiyoshi; Sugiyama, Azusa; Nemoto, Toru; Fujii, Hideaki; Wada, Keiji; Oka, Jun-Ichiro; Nagase, Hiroshi; Yamada, Mitsuhiko

2011-10-01

We previously reported that the δ opioid receptor (DOP) agonists SNC80 and TAN-67 produce potent antidepressant-like and antinociceptive effects in rodents. However, SNC80 produced convulsive effects. Recently, we succeeded in synthesizing a novel DOP agonist called KNT-127. The present study examined the convulsive, antidepressant-like, and antinociceptive effects of KNT-127 in mice. In contrast to SNC80, KNT-127 produced no convulsions at doses of up to 100mg/kg. In mice subjected to the forced swim test, a screening model for antidepressants, KNT-127 (1mg/kg, s.c.) significantly decreased the duration of immobility and increased the duration of swimming without influencing spontaneous locomotor activity. These behavioral changes were similar to that observed for the tricyclic antidepressant imipramine (6mg/kg). The antidepressant-like effect of KNT-127 in mice was antagonized by pretreatment with naltrindole (NTI), a selective DOP antagonist, or naltriben, a putative DOP(2) subtype antagonist. In addition, KNT-127 (3mg/kg, s.c.) significantly reduced the number of acetic acid-induced abdominal constrictions and the duration of licking time, respectively, in mice subjected to a writhing test and a formalin test. These antinociceptive effects were antagonized by pretreatment with either NTI or 7-benzylidenenaltrexone, a putative DOP(1) subtype antagonist. We propose that KNT-127 should be considered as a candidate compound for the development of DOP-based antidepressants and/or analgesics that lack convulsive effects. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.
Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae).

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Rinaldi, Sebastian; Silva, Davi O; Bello, Fabiana; Alviano, Celuta S; Alviano, Daniela S; Matheus, Maria Eline; Fernandes, Patricia D

2009-04-21

Cocos nucifera cultivated in Brazil is known as "coco-da-Bahia" or "coqueiro-da-India". The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera "common variety" were evaluated to test the anti-inflammatory and antinociceptive activities. Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50mg/kg), and the references drugs morphine (5mg/kg), acetilsalicilic acid (200mg/kg), prometazine (30 mg/kg), and metisergide (5mg/kg) were evaluated on models of analgesia and inflammation. CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin. results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.
Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats

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Kim, Hye-Jin; Lee, Geun-Woo; Kim, Min-Ji; Yang, Kui-Ye; Kim, Seong-Taek; Bae, Yong-Cheol

2015-01-01

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions. PMID:26170739
Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.

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Macedo, E M A; Santos, W C; Sousa, B P; Lopes, E M; Piauilino, C A; Cunha, F V M; Sousa, D P; Oliveira, F A; Almeida, F R C

2016-06-20

Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.
Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

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E.M.A. Macedo

2016-01-01

Full Text Available Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs. These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF (3.125 and 1.25 mg/kg po, respectively presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment and chronic (10 days inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA in the right hind paw of female Wistar rats (170-230 g, n=6-8. The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this
Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models

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Camila Carolina de Menezes Patrício Santos

2013-01-01

Full Text Available The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p. to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P<0.001. In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases, this effect being more pronounced in the second phase (P<0.001. Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS. Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.
Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

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M.A. Oliveira

1998-05-01

Full Text Available The antinociceptive effects of stimulating the medial (ME and central (CE nuclei of the amygdala in rats were evaluated by the changes in the latency for the tail withdrawal reflex to noxious heating of the skin. A 30-s period of sine-wave stimulation of the ME or CE produced a significant and short increase in the duration of tail flick latency. A 15-s period of stimulation was ineffective. Repeated stimulation of these nuclei at 48-h intervals produced progressively smaller effects. The antinociception evoked from the ME was significantly reduced by the previous systemic administration of naloxone, methysergide, atropine, phenoxybenzamine, and propranolol, but not by mecamylamine, all given at the dose of 1.0 mg/kg. Previous systemic administration of naloxone, atropine, and propranolol, but not methysergide, phenoxybenzamine, or mecamylamine, was effective against the effects of stimulating the CE. We conclude that the antinociceptive effects of stimulating the ME involve at least opioid, serotonergic, adrenergic, and muscarinic cholinergic descending mechanisms. The effects of stimulating the CE involve at least opioid, ß-adrenergic, and muscarinic cholinergic descending mechanisms.

Antinociceptive and Anti-Inflammatory Activity from Algae of the Genus Caulerpa

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Bárbara Viviana de Oliveira Santos

2011-03-01

Full Text Available Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME, acetate (AE, hexanic (HE and chloroform (CE extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o. did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism
In vivo antinociceptive and muscle relaxant activity of leaf and bark of Buddleja asiatica L.

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Barkatullah, -; Ibrar, Muhammad; Ikram, Nazia; Rauf, Abdur; Hadda, Taibi Ben; Bawazeer, Saud; Khan, Haroon; Pervez, Samreen

2016-09-01

The current study was designed to assess the antinociceptive and skeleton muscle relaxant effect of leaves and barks of Buddleja asiatica in animal models. In acetic acid induced writhing test, pretreatment of ethanolic extract of leaves and barks evoked marked dose dependent antinociceptive effect with maximum of 70% and 67% pain relief at 300mg/kg i.p. respectively. In chimney test, the ethanolic extract of leaves and barks evoked maximum of 66.66% and 53.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In traction test, the ethanolic extract of leaves and barks caused maximum of 60% and 73.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In short, both leaves and barks demonstrated profound antinociceptive and skeleton muscle relaxant effects and thus the study provided natural healing agents for the treatment of said disorders.
Evaluation and comparison of antinociceptive activity of aspartame with sucrose.

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Rani, Seema; Gupta, Mahesh C

2012-01-01

Artificial sweeteners are low-calorie substances used to sweeten a wide variety of foods. At present they are used increasingly not only by diabetics, but also by the general public as a mean of controlling the weight. This study was carried out to evaluate and compare antinociceptive activity of the artificial sweeteners, aspartame and sucrose and to study the mechanisms involved in this analgesic activity. Forty eight white albino Wistar rats were divided into two groups of 24 rats each. Group 1 received sucrose and group 2 received aspartame solution ad libitum for 14 days as their only source of liquid. On 14(th) day, both groups of rats were divided into 3 subgroups having 8 rats each. Group Ia and IIa served as control. Group Ib and IIb were given naloxone and Ic and IIc received ketanserin, the opioid and serotonergic receptor antagonists, respectively. Tail withdrawal latencies (tail flick analgesiometer) and paw licking/jumping latencies (Eddy's hot plate method) were increased significantly in both aspartame and sucrose group. The analgesia produced by aspartame was comparable with sucrose. The opioid receptor antagonist naloxone and the 5-HT(2A/2C) serotonergic receptor antagonist ketanserin partly reversed the antinociceptive effect of these sweeteners. Thus, the artificial sweetening agent aspartame showed antinociceptive activity like sucrose in rats. Reduction in antinociceptive activity of aspartame and sucrose by opioid and serotoninergic antagonists demonstrate the involvement of both opioid and serotonergic system.
Antinociceptive and antiedematogenic effect of pecan (Carya illinoensis) nut shell extract in mice: a possible beneficial use for a by-product of the nut industry.

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Trevisan, Gabriela; Rossato, Mateus F; Hoffmeister, Carin; Müller, Liz G; Pase, Camila; Córdova, Marina M; Rosa, Fernanda; Tonello, Raquel; Hausen, Bruna S; Boligon, Aline A; Moresco, Rafael N; Athayde, Margareth L; Burguer, Marilise E; Santos, Adair R; Ferreira, Juliano

2014-01-27

Abstract Background: Interest in pecan (Carya illinoensis) nut shells, a by-product of the nut industry, has increased due to its anti-inflammatory and antioxidant activities. The goal of this study was to evaluate the antinociceptive and antiedematogenic activity and the mechanisms of the pecan shell aqueous extract (AE). Methods: First, we performed fingerprinting of C. illinoensis AE. The antinociceptive and antiedematogenic effects of AE intragastric (i.g.) administration in mice (male Swiss mice 20-30 g) were evaluated using the acetic acid test or after subcutaneous (s.c.) paw injection of diverse transient receptor potential ankyrin 1 (TRPA1) agonists, including hydrogen peroxide (H2O2), allyl isothiocyanate, or cinnamaldehyde. We also observed AE antinociceptive and antiedematogenic effects after carrageenan s.c. paw injection and measured H2O2 production. Moreover, we observed the development of adverse effects after AE i.g. treatment. Results: The high-performance liquid chromatography fingerprinting of AE showed the presence of rutin. AE or rutin i.g. treatment produced antinociception in the acetic acid test and reduced the nociception and edema mediated by H2O2 s.c. hind paw injection or nociception induced by other TRPA1 agonists. Moreover, AE or rutin reduced the hyperalgesia, edema, and H2O2 production induced by carrageenan s.c. paw injection. No motor, gastric, or toxicological alterations were observed after AE administration. Conclusions: Collectively, the present results show that AE and its constituent rutin produced antinociceptive and antiedematogenic action in models of acute and persistent inflammatory nociception and it seems to be related to the inhibition of TRPA1 receptor activation.
Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

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Yuqing Mao

2017-09-01

Full Text Available Background/Aims: Irritable bowel syndrome (IBS, defined as recurrent abdominal pain and changes in bowel habits, seriously affects quality of life and ability to work. Ghrelin is a brain-gut hormone, which has been reported to show antinociceptive effects in peripheral pain. We investigated the effect of ghrelin on visceral hypersensitivity and pain in a rat model of IBS. Methods: Maternal deprivation (MD was used to provide a stress-induced model of IBS in Wistar rats. Colorectal distension (CRD was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR scores. Rats that were confirmed to have visceral hypersensitivity after MD were injected with ghrelin (10 µg/kg subcutaneously twice a week from weeks 7 to 8. [D-Lys3]-GHRP-6 (100 nmol/L and naloxone (100 nmol/L were administered subcutaneously to block growth hormone secretagogue receptor 1α (GHS-R1α and opioid receptors, respectively. Expression of transient receptor potential vanilloid type 1 (TRPV1 and µ and κ opioid receptors (MOR and KOR in colon, dorsal root ganglion (DRG and cerebral cortex tissues were detected by western blotting, quantitative real-time polymerase chain reaction (qRT-PCR, immunohistochemical analyses and immunofluorescence. Results: Ghrelin treatment increased expression of opioid receptors and inhibited expression of TRPV1 in colon, dorsal root ganglion (DRG and cerebral cortex. The antinociceptive effect of ghrelin in the rat model of IBS was partly blocked by both the ghrelin antagonist [D-Lys3]-GHRP-6 and the opioid receptor antagonist naloxone. Conclusion: The results indicate that ghrelin exerted an antinociceptive effect, which was mediated via TRPV1/opioid systems, in IBS-induced visceral hypersensitivity. Ghrelin might potentially be used as a new treatment for IBS.
Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice

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Diego C. Mascarenhas

2017-10-01

Full Text Available Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1 and Cannabinoid type 1 (CB1 receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist, capsaicin (TRPV1 agonist, WIN (CB1 agonist, AM251 (CB1 antagonist, and 6-iodonordihydrocapsaicin (6-IODO (TRPV1 selective antagonist and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1- and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.
Antinociceptive effects of tramadol hydrochloride after intravenous administration to Hispaniolan Amazon parrots (Amazona ventralis).

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Geelen, Saskia; Sanchez-Migallon Guzman, David; Souza, Marcy J; Cox, Sherry; Keuler, Nicholas S; Paul-Murphy, Joanne R

2013-02-01

To determine the antinociceptive and sedative effects of tramadol in Hispaniolan Amazon parrots (Amazona ventralis) following IV administration. 11 healthy Hispaniolan Amazon parrots of unknown sex. Tramadol hydrochloride (5 mg/kg, IV) and an equivalent volume (≤ 0.34 mL) of saline (0.9% NaCl) solution were administered to parrots in a complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 15, 30, 60, 120, and 240 minutes after treatment administration; agitation-sedation scores were determined for parrots at each of those times. The estimated mean changes in temperature from the baseline value that elicited a foot withdrawal response were 1.65° and -1.08°C after administration of tramadol and saline solution, respectively. Temperatures at which a foot withdrawal response was elicited were significantly higher than baseline values at all 5 evaluation times after administration of tramadol and were significantly lower than baseline values at 30, 120, and 240 minutes after administration of saline solution. No sedation, agitation, or other adverse effects were observed in any of the parrots after administration of tramadol. Tramadol hydrochloride (5 mg/kg, IV) significantly increased the thermal nociception threshold for Hispaniolan Amazon parrots in the present study. Sedation and adverse effects were not observed. These results are consistent with results of other studies in which the antinociceptive effects of tramadol after oral administration to parrots were determined.
Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain.

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Czopek, Anna; Sałat, Kinga; Byrtus, Hanna; Rychtyk, Joanna; Pawłowski, Maciej; Siwek, Agata; Soluch, Joanna; Mureddu, Valentina; Filipek, Barbara

2016-06-01

Antiepileptic drugs are commonly used in non-epileptic disorders. For example, phenytoin and levetiracetam demonstrate analgesic properties in rodent models of pain. In order to enhance their antinociceptive activity, structural features of phenytoin and levetiracetam, such as imidazolidine-2,4-dione and amide bond in alkyl chain, were combined in one molecule. Furthermore, in preliminary studies, methoxyphenylpiperazinpropyl derivatives of imidazolidine-2,4-dione acted as antinociceptive agents in several rodent models of acute pain. The final compounds and the reference drugs - levetiracetam and phenytoin were evaluated in the hot plate test to assess their antinociceptive activity in this acute pain model. Furthermore, for the analgesic active compounds the impact on animals' locomotor activity and motor performance were estimated and the affinity to serotonergic (5-HT1A, 5-HT7) and adrenergic (α1) receptors was determined. Three of the tested compounds: 7, 15 and 18 showed statistically significant antinociceptive properties at the dose of 30mg/kg. Among them, compound 18, 1-methyl-3-[1-(morpholin-4-yl)-1-oxobutan-2-yl]imidazolidine-2,4-dione, exhibited the most significant and long-lasting antinociceptive activity. Noteworthy, this activity was not associated with a negative effect on animals' motor functions. Serotonergic or adrenergic neurotransmission is not involved in this antinociceptive effect. Some amide derivatives of imidazolidine-2,4-diones possess antinociceptive properties in mice but further studies are needed to explain their mechanism of action and assess their toxicity. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

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Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

2014-01-01

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060
A Comparative Analysis of the Chemical Composition, Anti-Inflammatory, and Antinociceptive Effects of the Essential Oils from Three Species of Mentha Cultivated in Romania

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Cristina Mogosan

2017-02-01

Full Text Available This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint, Mentha spicata L. subsp. crispata (spearmint, and Mentha suaveolens Ehrh. (pineapple mint. Qualitative and quantitative analysis of the essential oils isolated from the selected Mentha species was performed by gas chromatography coupled with mass spectrometry (GC-MS. The anti-inflammatory activity of the essential oils was determined by the rat paw edema test induced by λ-carrageenan. The antinociceptive effect of the essential oils was evaluated by the writhing test in mice, using 1% (v/v acetic acid solution administered intraperitonealy and by the hot plate test in mice. The results showed a menthol chemotype for M. piperita pallescens, a carvone chemotype for M. spicata, and a piperitenone oxide chemotype for M. suaveolens. The essential oil from M. spicata L. (EOMSP produced statistically significant and dose-dependent anti-inflammatory and antinociceptive effects.
Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

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Md. Josim Uddin

2018-04-01

Full Text Available Anisomeles indica (L. kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models.
Evaluation of antinociceptive and antimicrobial activities of galbanum plant (Ferula gumosa Boiss

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B. S. Fazly Bazzaz

1997-08-01

Full Text Available To evaluate the antinociceptive and antimicrobial activities of galbanum plant (Ferula gumosa, various parts of the plant were collected at specific seasons. Aerial parts and root of the plant were dried in shady place and grinded to desirable. Unnatural and natural gum resins did not have the drying and grinding stages. The alcohol-aqueous (33%extract was obtained by masuration and the solvent was removed by rotary evaporator at low temperature and vaccum condition. The essential oil was extracted by water and steam distillation. Its antinociceptive effect was investigated in mice using hot plate method. Antibacterial effect was determined using paper disk method. The results suggest that the maximum antinociceptive effect (efficacy of root and aerial parts extract was higher than morphine and maximum effect of unnatural and natural gum resins extract was equal to morphine. The maximum effect of essential oil and unnatural gum resin was less than morphine but potency of these preparations were less than morphine. The amount of microbial growth inhibition of all extracts was less than chloramphenicol (30 ;ug on gram positive bacteria, but these extracts have not any growth inhibitory effect on gram negative baceria. These extracts inhibited fungus growth equal to nystatin (100units. "nThese results in conjunction with economic considerations suggest the usefulness of aerial parts of plant for medical treatment.
Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in mice.

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Vilela, Fabiana Cardoso; de Mesquita Padilha, Marina; Dos Santos-E-Silva, Lucas; Alves-da-Silva, Geraldo; Giusti-Paiva, Alexandre

2009-07-15

Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine. Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of hydroethanolic and dichloromethane extracts from aerial parts of Sonchus oleraceus in mice using chemical and thermal models of nociception. The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice. Given orally, the extracts at test doses of 30-300 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin since decreased the number of writhing episodes and the time licking. Treatment with the extracts in the same doses produced a significant increase of the reaction time in tail immersion and in the hot plate test. The extracts administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5mg/kg, p.o.) and morphine (10mg/kg, p.o.). The extracts of Sonchus oleraceus markedly demonstrated antinociceptive action in mice, which supports previous claims of its traditional use.
Recombinant mouse PAP has pH-dependent ectonucleotidase activity and acts through A(1-adenosine receptors to mediate antinociception.

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Nathaniel A Sowa

Full Text Available Prostatic acid phosphatase (PAP is expressed in nociceptive neurons and functions as an ectonucleotidase. When injected intraspinally, the secretory isoforms of human and bovine PAP protein have potent and long-lasting antinociceptive effects that are dependent on A(1-adenosine receptor (A(1R activation. In this study, we purified the secretory isoform of mouse (mPAP using the baculovirus expression system to determine if recombinant mPAP also had antinociceptive properties. We found that mPAP dephosphorylated AMP, and to a much lesser extent, ADP at neutral pH (pH 7.0. In contrast, mPAP dephosphorylated all purine nucleotides (AMP, ADP, ATP at an acidic pH (pH 5.6. The transmembrane isoform of mPAP had similar pH-dependent ectonucleotidase activity. A single intraspinal injection of mPAP protein had long-lasting (three day antinociceptive properties, including antihyperalgesic and antiallodynic effects in the Complete Freund's Adjuvant (CFA inflammatory pain model. These antinociceptive effects were transiently blocked by the A(1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX, suggesting mPAP dephosphorylates nucleotides to adenosine to mediate antinociception just like human and bovine PAP. Our studies indicate that PAP has species-conserved antinociceptive effects and has pH-dependent ectonucleotidase activity. The ability to metabolize nucleotides in a pH-dependent manner could be relevant to conditions like inflammation where tissue acidosis and nucleotide release occur. Lastly, our studies demonstrate that recombinant PAP protein can be used to treat chronic pain in animal models.
Study of antinociceptive effect of isolated fractions from Petiveria alliacea L. (tipi) in mice.

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Gomes, Patrícia Bezerra; Oliveira, Maria Mirele da Silva; Nogueira, Carlos Renato Alves; Noronha, Emmanuelle Coelho; Carneiro, Lyvia Maria Vasconcelos; Bezerra, José Noberto Sousa; Neto, Manoel Andrade; Vasconcelos, Silvania Maria Mendes; Fonteles, Marta Maria França; Viana, Glauce Socorro Barros; de Sousa, Francisca Clea Florenço

2005-01-01

The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of Petiveria alliacea L. were evaluated for antinociceptive effect using the abdominal constriction induced by acetic acid, hot-plate, formalin tests. The open field and rota rod tests were used to evaluate psychomotor function and myorelaxant activity. The fractions were administered intraperitoneally in mice at doses of 100 and 200 mg/kg. Inhibitions of abdominal constrictions were observed with all doses of the fractions, as compared to control. FH and FHAppt, at both doses, reduced the nociception produced by formalin in the 1st (0-5 min) and 2nd (20-25 min) phases, however FHA (100, 200 mg/kg) and FA 200 mg/kg presented significant inhibition on the 1st and 2nd phases, respectively, of this test. A reduction of the locomotor activity was observed in the open field test with all the fractions. These fractions failed to affect the motor coordination in the rota rod test. Results showed that the different fractions of Petiveria alliacea L. have different antinociceptive potentials as demonstrated in the experimental models of nociception in mice, supporting folk medicine use of this plant.
Antinociceptive activity of Astragalus gummifer gum (gum tragacanth) through the adrenergic system: A in vivo study in mice.

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Bagheri, Seyyed Majid; Keyhani, Leila; Heydari, Mehrangiz; Dashti-R, Mohammad Hossein

2015-01-01

In Iranian traditional medicine, gum obtained from Astragalus gummifer and some other species of Astragalus was used as analgesic agent. In this study, we investigated the antinociceptive effect of several concentrations (125, 250, and 500 μg/kg body weight) of Astragalus gummifer gum (AGG) on thermal and acetic acid induced pain in mice. AGG was dissolved in distillated water and injected i.p to male mice 15 minute before the onset of experiment. Writhing and hot-plate tests were applied to study the analgesic effect of AGG and compared with that of diclofenac sodium (30 mg/kg, i.p.) or morphine (8 mg/kg, i.p). To investigate the mechanisms involved in antinociception, yohimbine, naloxone, glibenclamide, and theophylline were used in writhing test. These drugs were injected intraperitoneally 15 min before the administration of AGG. The number of writhes were counted in 30 minutes and analyzed. AGG exhibited a significant antinociceptive effect and the most effective dose of AGG was 500 μg/kg. The most maximum possible effect (%MPE) was observed (117.4%) 15 min after drug administration. The %inhibition of acetic acid-induced writhing in AGG 125, 250 and 500 was 47%, 50% and 54% vs %15 of control and 66.3% of diclofenac sodium group. The antinociceptive effect induced by this gum in the writhing test was reversed by the systemic administration of yohimbine (α2-adrenergic antagonist), but naloxone, glibenclamide, and theophylline did not reverse this effect. The findings of this study indicated that AGG induced its antinociceptive through the adrenergic system.
Evaluation of long-term antinociceptive properties of stabilized hyaluronic acid preparation (NASHA) in an animal model of repetitive joint pain

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2011-01-01

Introduction Clinical trials provided controversial results on whether the injection of hyaluronan preparations into osteoarthritic joints reduces pain. Problems of clinical studies may be the substantial placebo effects of intra-articular injections, different severity and rate of progression of the disease and others. We hypothesize that the use of preclinical pain models may help to clarify whether a certain hyaluronan exerts antinociceptive effects upon intra-articular injection. In the present study we tested in the bradykinin/prostaglandin E2 (PGE2) model primarily the putative antinociceptive effect of stabilized hyaluronic acid from a non animal source (NASHA), a stabilized hyaluronic acid based gel for intra-articular treatment of OA. We established a dose-response relationship for NASHA and we compared NASHA to other hyaluronans with different formulations that are in clinical use. Methods To induce transient joint pain episodes bradykinin and PGE2 were repetitively administered intra-articularly and unilaterally into rat knee joints during short anaesthesia. After establishment of the predrug nociceptive responses, a single intra-articular injection of saline or NASHA at different concentrations was administered and pain responses to further bradykinin/PGE2 injections were monitored up to 56 days after NASHA. Furthermore, the obtained effective dose was compared to clinically defined concentrations of Hylan GF20 and sodium hyaluronate. The primary outcome measures were primary mechanical hyperalgesia at the knee joint and pain-induced weight bearing. Results On day 1 after injection, all tested hyaluronan preparations showed an antinociceptive effect >50% compared to saline. Single injections of higher doses of NASHA (50, 75 and 100 μl) were antinociceptive up to 56 days. When injection volumes in rat knee joints were adapted to clinical injection volumes in humans, the antinociceptive effects of the cross-linked NASHA and Hylan GF20 had a longer
Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

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Elham A. Afify

2017-11-01

Full Text Available Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate, (visceral, acetic acid, and (inflammatory, formalin test in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.
Isobolographic analysis of the antinociceptive interaction between ursolic acid and diclofenac or tramadol in mice.

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Déciga-Campos, Myrna; Cortés, Alejandra; Pellicer, Francisco; Díaz-Reval, Irene; González-Trujano, María Eva

2014-02-01

It is considered that natural products used in folk medicine can potentiate the effect of drugs. The aim of this study was to evaluate the pharmacological interaction between ursolic acid, a triterpene isolated from herbal medicines to treat pain, and the analgesics diclofenac or tramadol. Individual dose-response curves of the antinociceptive effect of these compounds were built to calculate the ED50, as well as the pharmacological interaction, by using isobolographic analysis. All treatments decreased significantly and in a dose-dependent manner the writhing behavior with ED50 values of 103.50 ± 19.66, 20.54 ± 6.05, and 9.60 ± 1.69 mg/kg, for ursolic acid, diclofenac, and tramadol, respectively. An isobolographic analysis allowed the characterization of the pharmacological interaction produced by a fixed ratio combination of 1 : 1 and 1 : 3 of equi-effective doses of these compounds. Theoretical antinociceptive ED50 values of ursolic acid-diclofenac were 62.12 ± 10.28 and 41.43 ± 6.69 mg/kg, respectively, not statistically different from those obtained experimentally (44.52 ± 5.25 and 44.89 ± 49.05 mg/kg, respectively), reporting an additive interaction. Theoretical antinociceptive ED50 values of ursolic acid-tramadol (56.56 ± 9.87 and 33.08 ± 5.07 mg/kg, respectively) were significantly lower than those observed experimentally (138.36 ± 49.05 and 67.34 ± 18.98 mg/kg, respectively) reporting antagonism in this interaction. Antinociceptive response obtained from isobolograms in the writhing test was corroborated by using formalin test in mice. Adverse effects such as gastric damage in the ursolic acid-diclofenac combination did not increase in an additive form similarly as with antinociception. Conversely, sedative response was significantly increased in the ursolic acid-tramadol combination. As observed in the formalin test, the antagonism on the antinociceptive response between ursolic acid
Phytochemical composition and antinociceptive activity of Bauhinia glauca subsp. hupehana in rats.

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Xu, Jinlong; Zhao, Qizhi; Wei, Lei; Yang, Yu; Xu, Rui; Yu, Nengjiang; Zhao, Yimin

2015-01-01

In traditional medicine, Bauhinia glauca subsp. hupehana has long been used as an analgesic agent in China. The aim of this study was to evaluate the antinociceptive activity of the ethanol extract of the aerial parts of B. glauca subsp. hupehana (BHE) in rats and its chemical fingerprint. The antinociceptive activity of BHE was assessed in mice using chemically and heat-induced pain models, such as the acetic acid-induced writhing, hot plate, tail-flick and glutamate tests. Naltrexone hydrochloride, a non-selective opioid receptor antagonist, was utilized to determine the involvement of the opioid system. In addition to this, the involvements of the cGMP and ATP-sensitive K+ channel pathways were also detected using methylene blue and glibenclamide. The oral administration of BHE (at doses of 50, 100 and 200 mg/kg) produced significant and dose-related inhibitions in both the chemically and heat-induced pain models. Interestingly, in the abdominal constriction test, when the dose of BHE was increased to 800 mg/kg (p.o., n = 10), the inhibition rate was 100%. The antinociceptive mechanism may involve the cGMP pathway and ATP sensitive K+ channel pathway. The central antinociceptive effect was not antagonized by naltrexone. One phenolic acid, one lignin and five flavonoids were isolated from BHE. The antinociceptive activity of BHE was most likely due to the presence of the flavonoids. The acute toxicity results showed that BHE was safe at a high dose (2 g/kg, p.o.). The current investigation demonstrates that B. glauca subsp. hupehana is a potential candidate for the development of novel, non-opioid, analgesic phytomedicines.

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

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de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro

2017-04-01

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.
Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract

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Cínthia R. C. Porto

2013-02-01

Full Text Available Phyllanthus niruri L., Euphorbiaceae, spray-dried standardized extract was studied for its anti-inflammatory and antinociceptive activities in adult albino rats and mice. The anti-inflammatory effect of spray-dried standardized extract was observed in carrageenan-induced paw edema and thioglycolate-induced leukocyte migration, while antinociceptive effects were observed using Randall & Selitto, tail flick, and hot plate tests. This study showed that intraperitoneal spray-dried standardized extract at 100, 200, 800, or 1600 mg/kg reduced the vascular response in the inflammatory process of paw edema induced by 1% carrageenan. Oral spray-dried standardized extract at 100 or 200 mg/kg inhibited leukocyte migration to the site of inflammation induced by 3% thioglycolate. In rats, at 100 and 200 mg/kg intraperitoneally, the extract exhibited a marked peripheral analgesic effect in a Randall & Selitto assay and showed significant central analgesic activity in a hot plate and tail flick assay. In conclusion, this study suggested that Phyllanthus niruri spray-dried standardized extract has potent inflammatory and antinociceptive activities and that these activities are not modified by standard drying process, making it feasible to use the dry extract standardized to obtain a phytotherapic preparation and thus validating its use for the treatment of pain and inflammation disorders.
Antinociceptive Activity of Thymoquinone and its Structural Analogues

African Journals Online (AJOL)

Methods: The quinones were prepared by an oxidation procedure using molecular oxygen and catalysis with [CoII(salen)] from ... mg/kg, ip) was evaluated using formalin test in mice. Vehicle (5 % Tween ... oxidation reactions. ... with 0.1 mol∙L-1 HCl (2 × 10 mL), water and brine. .... antinociceptive effect in the acetic acid and.
Stress-induced antinociception in fish reversed by naloxone.

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Carla Patrícia Bejo Wolkers

Full Text Available Pain perception in non-mammalian vertebrates such as fish is a controversial issue. We demonstrate that, in the fish Leporinus macrocephalus, an imposed restraint can modulate the behavioral response to a noxious stimulus, specifically the subcutaneous injection of 3% formaldehyde. In the first experiment, formaldehyde was applied immediately after 3 or 5 min of the restraint. Inhibition of the increase in locomotor activity in response to formaldehyde was observed, which suggests a possible restraint-induced antinociception. In the second experiment, the noxious stimulus was applied 0, 5, 10 and 15 min after the restraint, and both 3 and 5 min of restraint promoted short-term antinociception of approximately 5 min. In experiments 3 and 4, an intraperitoneal injection of naloxone (30 mg.kg(-1 was administered 30 min prior to the restraint. The 3- minute restraint-induced antinociception was blocked by pretreatment with naloxone, but the corresponding 5-minute response was not. One possible explanation for this result is that an opioid and a non-preferential μ-opioid and/or non-opioid mechanism participate in this response modulation. Furthermore, we observed that both the 3- and 5- minutes restraint were severely stressful events for the organism, promoting marked increases in serum cortisol levels. These data indicate that the response to a noxious stimulus can be modulated by an environmental stressor in fish, as is the case in mammals. To our knowledge, this study is the first evidence for the existence of an endogenous antinociceptive system that is activated by an acute standardized stress in fish. Additionally, it characterizes the antinociceptive response induced by stress in terms of its time course and the opioid mediation, providing information for understanding the evolution of nociception modulation.
Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

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Pirkulashvili N

2017-07-01

Full Text Available Natia Pirkulashvili,1 Nana Tsiklauri,1 Marina Nebieridze,2 Merab G Tsagareli1 1Laboratory of Pain and Analgesia, 2Laboratory of Brain Metabolism, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia Abstract: Several lines of investigations have shown that in some brain areas, in particular, in the midbrain periaqueductal gray matter, rostral ventromedial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs induce antinociception with distinct development of tolerance. The agranular insular cortex (AIC is a small region of the cerebral cortex located on the lateral area of the rat’s cerebral hemisphere that is involved in the perception and response to pain. In the present study, we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac, and xefocam microinjected into the AIC in rats. Male Wistar rats receiving NSAIDs into the AIC were tested for antinociception by tail-flick and hot plate tests. Treatment with each NSAID significantly enhanced the tail-flick and hot plate latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, ie, they developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented, and posttreatment naloxone abolished, the analgesic effects of the three NSAIDs in both behavioral assays. These findings support the notion that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems. Keywords: antinociception, endogenous opioids, descending modulation, nociception, nonopioid tolerance
Antinociceptive activity of Astragalus gummifer gum (gum tragacanth through the adrenergic system: A in vivo study in mice

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Seyyed Majid Bagheri

2015-01-01

Full Text Available Background: In Iranian traditional medicine, gum obtained from Astragalus gummifer and some other species of Astragalus was used as analgesic agent. Objective: In this study, we investigated the antinociceptive effect of several concentrations (125, 250, and 500 μg/kg body weight of Astragalus gummifer gum (AGG on thermal and acetic acid induced pain in mice. Materials and Methods: AGG was dissolved in distillated water and injected i.p to male mice 15 minute before the onset of experiment. Writhing and hot-plate tests were applied to study the analgesic effect of AGG and compared with that of diclofenac sodium (30 mg/kg, i.p. or morphine (8 mg/kg, i.p. To investigate the mechanisms involved in antinociception, yohimbine, naloxone, glibenclamide, and theophylline were used in writhing test. These drugs were injected intraperitoneally 15 min before the administration of AGG. The number of writhes were counted in 30 minutes and analyzed. Results: AGG exhibited a significant antinociceptive effect and the most effective dose of AGG was 500 μg/kg. The most maximum possible effect (%MPE was observed (117.4% 15 min after drug administration. The %inhibition of acetic acid-induced writhing in AGG 125, 250 and 500 was 47%, 50% and 54% vs %15 of control and 66.3% of diclofenac sodium group. The antinociceptive effect induced by this gum in the writhing test was reversed by the systemic administration of yohimbine (α2 -adrenergic antagonist, but naloxone, glibenclamide, and theophylline did not reverse this effect. Conclusions: The findings of this study indicated that AGG induced its antinociceptive through the adrenergic system.
Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

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Orhan, I; Küpeli, E; Aslan, M; Kartal, M; Yesilada, E

2006-04-21

The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.
Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat.

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Haghparast, Abbas; Soltani-Hekmat, Ava; Khani, Abbas; Komaki, Alireza

2007-10-29

Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia. Previous studies have shown that antinociceptive response of CnF-microinjected morphine can be modulated by the specific subtypes of glutamatergic receptors within the CnF. In this study, we evaluated the role of NMDA and kainate/AMPA receptors that are widely distributed within the NRM on morphine-induced antinociception elicited from the CnF. Hundred and five male Wistar rats weighing 250-300 g were used. Morphine (10, 20 and 40 microg) and NMDA receptor antagonist, MK-801 (10 microg) or kainate/AMPA receptor antagonist, DNQX (0.5 microg) in 0.5 microl saline were stereotaxically microinjected into the CnF and NRM, respectively. The latency of tail-flick response was measured at set intervals (2, 7, 12, 17, 22, 27 min after microinjection) by using an automated tail-flick analgesiometer. The results showed that morphine microinjection into the CnF dose-dependently causes increase in tail-flick latency (TFL). MK-801 microinjected into the NRM, just 1 min before morphine injection into the CnF, significantly attenuated antinociceptive effects of morphine. On the other hand, DNQX microinjected into the NRM, significantly increased TFL after local application of morphine into the CnF. We suggest that morphine related antinociceptive effect elicited from the CnF is mediated, in part, by NMDA receptor at the level of the NRM whereas kainite/AMPA receptor has a net inhibitory influence at the same pathway.
Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

African Journals Online (AJOL)

Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...
Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice

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Masocha, Willias; Kombian, Samuel B.; Edafiogho, Ivan O.

2016-02-01

Recently, we found that methyl 4-(4‧-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4‧-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4‧-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin. Tiagabine had antinociceptive activity in both phase 1 (neurogenic pain) and phase 2 (inflammatory pain) of the formalin test, whereas indomethacin had activity only in phase 2. E139 and E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2. E122 had no significant activity in either phase. In the hot plate test only E139 had antinociceptive activity. Administration of either bicuculline, a GABAA receptor antagonist, or CGP 35348, a GABAB receptor antagonist, blocked the antinociceptive activity of E139. In conclusion our results indicate that E139 has antinociceptive activity in the formalin and hot plate tests that are dependent on GABA receptors.
Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet.

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Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; García-Martínez, Betzabeth Anali; López-Muñoz, Francisco Javier

2016-10-05

Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception ("plantar test" method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestrogenic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8-100mg/kg p.o.), were evaluated in all groups. The administration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen. Copyright © 2016 Elsevier B.V. All rights reserved.
Antinociceptive Effect of Morphine Microinjections into the Dorsal Hippocampus in the Formalin-Induced Orofacial Pain in Rats

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Emad Khalilzadeh

2010-09-01

Full Text Available In the present study, the effects of intra-hippocampal microinjections of morphine (an opioid agonist and naloxone (an opioid antagonist were investigated in the formalin-induced orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1 %, 50 μl in the upper lip region and the time spent of face rubbing was measured in 3-min blocks for 45 min. Formalin induced a biphasic (first phase: 0-3 min; second phase: 15-33 min pain response. Intra-hippocampal microinjections of morphine at doses of 2 and 4 μg significantly (P < 0.05 attenuated the first phase, and at doses of 1, 2 and 4 μg, morphine significantly (P < 0.05 suppressed both phases of formalin-induced orofacial pain response. Intra-hippocampal microinjections of naloxone (1 and 4 μg non-significantly increased pain when used alone, and in pretreatment microinjection, naloxone (4 μg reversed morphine (2 μg-induced antinociception. These results indicate that at the level of hippocampus of the brain, morphine through a naloxone-reversible mechanism produced an antinociceptive effect confronting the pain induced by formalin in the orofacial region in rats.
Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

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Leite-Panissi C.R.A.

2004-01-01

Full Text Available Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol and morphine (2.2 nmol into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10 was blocked by previous administration of atropine (0.7 nmol; N = 7 or naloxone (1.3 nmol; N = 7 into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9 into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11. All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.
Antinociceptive and anti-inflammatory activities of Cuscuta chinensis seeds in mice.

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Liao, Jung-Chun; Chang, Wen-Te; Lee, Meng-Shiou; Chiu, Yung-Jia; Chao, Wei-Kai; Lin, Ying-Chih; Lin, Ming-Kuem; Peng, Wen-Huang

2014-01-01

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p Cuscutae Semen in inflammatory diseases.
In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

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Khan, Haroon; Khan, Murad Ali; Hussain, Sajid; Gaffar, Rukhsana; Ashraf, Nadeem

2016-05-01

Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models. © The Author(s) 2013.
Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

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Liu, Jean; Reid, Allison R; Sawynok, Jana

2013-03-01

Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
SPINAL ANTINOCICEPTION BY MORPHINE IN RATS IS ANTAGONIZED BY GALANIN RECEPTOR ANTAGONISTS

NARCIS (Netherlands)

REIMANN, W; ENGLBERGER, W; FRIDERICHS, E; SELVE, N; WILFFERT, B

1994-01-01

Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal
Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

Science.gov (United States)

Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

2014-01-01

To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Antinociceptive Activity of the Chloroform Fraction of Dioclea virgata (Rich. Amshoff (Fabaceae in Mice

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Vanine Gomes Mota

2011-01-01

Full Text Available Acute treatment with the chloroform fraction of Dioclea virgata (Rich. Amshoff (CFDv in mice produced decreased ambulation and sedation in the behavioral pharmacological screening. Doses of 125 and 250 mg/kg CFDv decreased latency of sleep onset in the test of sleeping time potentiation. In the open field, animals treated with CFDv reduced ambulation and rearing (250 mg/kg, as well as defecation (125; 250 mg/kg. Regarding the antinociceptive activity, CFDv (125, 250, 500 mg/kg increased latency to first writhing and decreased the number of writhings induced by acetic acid. In the formalin test, CFDv (250 mg/kg decreased paw licking time in the first and second phases indicating antinociceptive activity that can be mediated both peripherally and at the central level. CFDv did not affect motor coordination until 120 minutes after treatment. CFDv shows psychopharmacological effects suggestive of CNS-depressant drugs with promising antinociceptive activity.
Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation

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Hugo Castro-Faria-Neto

2013-04-01

Full Text Available Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2 in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.

The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes

DEFF Research Database (Denmark)

Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

2010-01-01

% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild......-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone...
Additive antinociceptive effects of a combination of vitamin C and vitamin E after peripheral nerve injury.

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Ruirui Lu

Full Text Available Accumulating evidence indicates that increased generation of reactive oxygen species (ROS contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.
Phytochemical screening, antinociceptive and anti-inflammatory effects of the essential oil of Myrcia pubiflora in mice

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Gilmara S. Andrade

2011-11-01

Full Text Available This report aimed to investigate the chemical composition and possible antinociceptive and anti-inflammatory effects of the essential oil from fresh leaves of Myrcia pubiflora DC., Myrtaceae (EOMP, through different experimental tests. The essential oil of M. pubiflora (EOMP was obtained by hydrodistillation, analyzed by GC-MS, and tested at doses of 25, 50, and 100 mg/kg (i.p. in three different tests of nociception (acetic acid-induced writhing test, formalin test, and hot plate test and one test of inflammation (leukocyte migration to the peritoneal cavity in order to evaluate the motor activity in mice treated with EOMP. The major component of EOMP was caryophyllene oxide (22.16%. This oil significantly reduced the number of writhes in an acetic acid test and the time spent licking the paw at the second phase of the formalin test. Furthermore, EOMP inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. However, administration of EOMP did not alter reaction time in the hot plate test, and did not affect the motor coordination test. These results indicate antinociceptive and anti-inflammatory properties of EOMP probably mediated via inhibition of inflammatory mediator synthesis or other peripheral pathway.
Phytochemical screening, antinociceptive and anti-inflammatory effects of the essential oil of Myrcia pubiflora in mice

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Gilmara S. Andrade

2012-02-01

Full Text Available This report aimed to investigate the chemical composition and possible antinociceptive and anti-inflammatory effects of the essential oil from fresh leaves of Myrcia pubiflora DC., Myrtaceae (EOMP, through different experimental tests. The essential oil of M. pubiflora (EOMP was obtained by hydrodistillation, analyzed by GC-MS, and tested at doses of 25, 50, and 100 mg/kg (i.p. in three different tests of nociception (acetic acid-induced writhing test, formalin test, and hot plate test and one test of inflammation (leukocyte migration to the peritoneal cavity in order to evaluate the motor activity in mice treated with EOMP. The major component of EOMP was caryophyllene oxide (22.16%. This oil significantly reduced the number of writhes in an acetic acid test and the time spent licking the paw at the second phase of the formalin test. Furthermore, EOMP inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. However, administration of EOMP did not alter reaction time in the hot plate test, and did not affect the motor coordination test. These results indicate antinociceptive and anti-inflammatory properties of EOMP probably mediated via inhibition of inflammatory mediator synthesis or other peripheral pathway.
Activity-Guided Isolation of Bioactive Constituents with Antinociceptive Activity from Muntingia calabura L. Leaves Using the Formalin Test

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Mohd. Izwan Mohamad Yusof

2013-01-01

Full Text Available The present study was conducted to determine the antinociceptive potential of methanol extract of Muntingia calabura L. (MEMC and to isolate and identify the bioactive compound(s responsible for the observed antinociceptive activity. The MEMC and its partitions (petroleum ether (PEP, ethyl acetate (EAP, and aqueous (AQP partitions, in the dose range of 100, 500, and 1000 mg/kg, were tested using the formalin-induced nociceptive test. The PEP, which exerted the most effective activity in the respective early and late phase, was further subjected to the fractionation procedures and yielded seven fractions (labelled A to G. These fractions were tested, at the dose of 300 mg/kg, together with distilled water or 10% DMSO (negative controls; morphine and aspirin (positive controls for potential antinociceptive activity. Of all fractions, Fraction D showed the most significant antinociceptive activity, which is considered as equieffective to morphine or aspirin in the early or late phase, respectively. Further isolation and identification processes on fraction D led to the identification of three known and one new compounds, namely, 5-hydroxy-3,7,8-trimethoxyflavone (1, 3,7-dimethoxy-5-hydroyflavone (2, 2′,4′-dihydroxy-3′-methoxychalcone (3, and calaburone (4. At the dose of 50 mg/kg, compound 3 exhibited the highest percentage of antinociceptive activity in both phases of the formalin test. In conclusion, the antinociceptive activity of MEMC involved, partly, the synergistic activation of the flavonoid types of compounds.
Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

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Birol Muhammet Er; İsmail Serhat Kocamanoğlu; Ayhan Bozkurt; Sırrı Bilge; Erhan Çetin Çetinoğlu

2016-01-01

Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. ...
Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol.

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Miranda, Hugo F; Puig, Margarita M; Dursteler, Christian; Prieto, Juan Carlos; Pinardi, Gianni

2007-02-01

The antinociceptive activity of dexketoprofen was studied in mice using the acetic acid writhing test (acute tonic pain), the tail flick test (acute phasic pain) and the formalin assay (inflammatory pain). Isobolographic analysis was used to study the antinociceptive interactions between morphine and paracetamol co-administered with dexketoprofen. In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen. In the tail flick test, the curves were parallel with similar efficacy and potency. The administration of morphine or paracetamol in both tests resulted in dose-response curves not parallel with that of dexketoprofen, which showed a potency between morphine and paracetamol. In the formalin assay, the antinociceptive activity of morphine during phase I was 122, 295 and 1695 times higher than dexketoprofen, ketoprofen and paracetamol, respectively. Isobolographic analysis demonstrated that the combination of sub-analgesic doses of dexketoprofen with morphine or with paracetamol was strongly synergic in all three tests. Synergistic drug combinations should improve effective pharmacological treatment of pain, minimizing drug specific adverse effects. These findings are undoubtedly worthy of additional controlled clinical trials in severe pain syndromes.
Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly selective delta-opioid receptor agonist.

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Improta, G; Broccardo, M

1992-01-01

Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.
Anti-Inflammatory and Antinociceptive Effects of Ethyl Acetate Fraction of an Edible Red Macroalgae Sarcodia ceylanica

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Chieh-Chih Shih

2017-11-01

Full Text Available Research so far has only shown that edible red macroalgae, Sarcodia ceylanica has the ability to eliminate free radicals and anti-diabetic, anti-bacterial properties. This study was conducted both in vitro and in vivo on the ethyl acetate extract (PD1 of farmed red macroalgae in order to explore its anti-inflammatory properties. In order to study the in vitro anti-inflammatory effects of PD1, we used lipopolysaccharide (LPS to induce inflammatory responses in murine macrophages. For evaluating the potential in vivo anti-inflammatory and antinociceptive effects of PD1, we used carrageenan-induced rat paw edema to produce inflammatory pain. The in vitro results indicated that PD1 inhibited the LPS-induced pro-inflammatory protein, inducible nitric oxide synthase (iNOS in macrophages. Oral PD1 can reduce carrageenan-induced paw edema and inflammatory nociception. PD1 can significantly inhibit carrageenan-induced leukocyte infiltration, as well as the protein expression of inflammatory mediators (iNOS, interleukin-1β, and myeloperoxidase in inflammatory tissue. The above results indicated that PD1 has great potential to be turned into a functional food or used in the development of new anti-inflammatory and antinociceptive agents. The results from this study are expected to help scientists in the continued development of Sarcodia ceylanica for other biomedical applications.
Electroacupuncture Confers Antinociceptive Effects via Inhibition of Glutamate Transporter Downregulation in Complete Freund's Adjuvant-Injected Rats

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Ha-Neui Kim

2012-01-01

Full Text Available When we evaluated changes of glial fibrillary acidic protein (GFAP and two glutamate transporter (GTs by immunohistochemistry, expression of GFAP showed a significant increase in complete Freund's adjuvant (CFA-injected rats; however, this expression was strongly inhibited by electroacupuncture (EA stimulation. Robust downregulation of glutamate-aspartate transporter (GLAST and glutamate transporter-1 (GLT-1 was observed in CFA-injected rats; however, EA stimulation resulted in recovery of this expression. Double-labeling staining showed co-localization of a large proportion of GLAST or GLT-1 with GFAP. Using Western blot, we confirmed protein expression of two GTs, but no differences in the mRNA content of these GTs were observed. Because EA treatment resulted in strong inhibition of CFA-induced proteasome activities, we examined the question of whether thermal sensitivities and GTs expression could be regulated by proteasome inhibitor MG132. CFA-injected rats co-treated with EA and MG132 showed a significantly longer thermal sensitivity, compared with CFA-injected rats with or without MG132. Both EA and MG132 blocked CFA-induced GLAST and GLT-1 downregulation within the spinal cord. These results provide evidence for involvement of GLAST and GLT-1 in response to activation of spinal astrocytes in an EA antinociceptive effect. Antinociceptive effect of EA may be induced via proteasome-mediated regulation of spinal GTs.
Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice.

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Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Micov, Ana M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-02-25

Antiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40mg/kg; p.o.) and oxcarbazepine (20-80mg/kg; p.o.) produced a significant, dose-dependent antinociception in diabetic mice while amitriptyline (5-60mg/kg; p.o.) produced weak antinociceptive effect. In normal mice, neither of the drugs produced antinociception. Gabapentin and oxcarbazepine, co-administered in fixed-dose fractions of the ED(50) to diabetic mice, induced significant, dose-dependent antinociception. Isobolographic analysis revealed synergistic interaction. Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and dose-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.
Evaluation of antinociceptive activity of aqueous extract of bark of psidium guajava in albino rats and albino mice.

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Sekhar, N Chandra; Jayasree, T; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-09-01

Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. AEPG antinociceptive activity involves activation of the peripheral and central mechanisms.
Evaluation of Anti-Nociceptive and Anti-Inflammatory Activities of a Heterofucan from Dictyota menstrualis

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Helena Bonciani Nader

2013-08-01

Full Text Available Fucan is a term that defines a family of homo- and hetero-polysaccharides containing sulfated l-fucose in its structure. In this work, a heterofucan (F2.0v from the seaweed, Dictyota menstrualis, was evaluated as an antinociceptive and anti-inflammatory agent. F2.0v (20.0 mg/kg inhibits 100% of leukocyte migration into the peritoneal cavity after chemical stimulation. However, F2.0v does not alter the expression of interleukin-1 beta (IL-1β and interleukin-6 (IL-6, as well as tumor necrosis factor alpha (TNF-α. F2.0v (20.0 mg/kg has peripheral antinociceptive activity with potency similar to dipyrone. On the other hand, it had no effect on pain response on the hot plate test. Confocal microscopy analysis and flow cytometry showed that F2.0v binds to the surface of leucocytes, which leads us to suggest that the mechanism of action of anti-inflammatory and antinociceptive F2.0v is related to its ability to inhibit the migration of leukocytes to the site of tissue injury. In summary, the data show that F2.0v compound has great potential as an antinociceptive and anti-inflammatory, and future studies will be performed to further characterize the mechanism of action of F2.0v.
Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

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Houria Manouze

2017-09-01

Full Text Available Anacyclus pyrethrum (L. is a plant widely used in Moroccan traditional medicine to treat inflammatory and painful diseases. The objective of the present study was to evaluate the antinociceptive, anti-inflammatory and antioxidant activities of aqueous and methanol extracts of Anacyclus pyrethrum roots (AEAPR and MEAPR. The anti-inflammatory effect of AEAPR and MEAPR was determined in xylene–induced ear edema and Complete Freund’s Adjuvant (CFA-induced paw edema. The antinociceptive activity of AEAPR and MEAPR (125, 250, and 500 mg/kg administered by gavage was examined in mice by using acetic acid-induced writhing, hot plate, and formalin tests, and the mechanical allodynia were assessed in CFA-induced paw edema. In addition, the in vitro antioxidant activities of the extracts were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging method, ferric reducing power and β-carotene-linoleic acid assay systems. AEAPR and MEAPR produced significant reductions in CFA-induced paw edema and xylene-induced ear edema. A single oral administration of these extracts at 250 and 500 mg/kg significantly reduced mechanical hypersensitivity induced by CFA, which had begun 1 h 30 after the treatment, and was maintained till 7 h. Chronic treatment with both extracts significantly reduced mechanical hypersensitivity in persistent pain conditions induced by CFA. Acute pretreatment with AEAPR or MEAPR at high dose caused a significant decrease in the number of abdominal writhes induced by acetic acid injection (52.2 and 56.7%, respectively, a marked increase of the paw withdrawal latency in the hot plate test, and also a significant inhibition of both phases of the formalin test. This antinociceptive effect was partially reversed by naloxone pretreatment in the hot plate and formalin tests. Additionally, a significant scavenging activity in DPPH, reducing power and protection capacity of β-carotene was observed in testing antioxidant assays
Pterodon pubescens Benth: stability study of microencapsulated extract and isolated compounds monitored by antinociceptive assays

International Nuclear Information System (INIS)

Servat, Leila; Spindola, Humberto M.; Carvalho, Joao E. de; Foglio, Mary A.; Rodrigues, Rodney A.F.; Sousa, Ilza M.O.; Ruiz, Ana L.T.G.

2012-01-01

Pterodon pubescens Benth. (Pp) seeds, commercially available in Brazil, are used in folk medicine in anti-inflammatory, analgesic, and anti-rheumatic preparations. The present study demonstrated the antinociceptive properties of isomers 6a-hydroxy-7β-acetoxy-vouacapan-17β--oate methyl ester and 6a-acetoxy-7β-hydroxy-vouacapan-17β-oate methyl ester (C1), isolated from (Pp), employing different experimental models. A stability study was performed to investigate the relationship of microencapsulation by spray-drying on the maintenance of antinociceptive action. Therefore, C1 and Pp extract samples were monitored in accelerated stability study, evaluating both microencapsulated and non-microencapsulated samples. It was observed that sample C1 possess antinociceptive activity revealed by writhing and formalin tests; C1 showed significantly anti-allodynic, but not ntihyperalgesic effect; the microencapsulation maintained the activity and integrity of both, sample C1 and Pp crude extract; microencapsulation by spray drying is a useful alternative to increase shelf life. (author)
Antinociceptive and Antibacterial Properties of Anthocyanins and Flavonols from Fruits of Black and Non-Black Mulberries

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Hu Chen

2017-12-01

Full Text Available Anthocyanins and flavones are important pigments responsible for the coloration of fruits. Mulberry fruit is rich in anthocyanins and flavonols, which have multiple uses in traditional Chinese medicine. The antinociceptive and antibacterial activities of total flavonoids (TF from black mulberry (MnTF, TF of Morus nigra and non-black mulberry (MmTF, TF of Morus mongolica; and MazTF, TF of Morus alba ‘Zhenzhubai’ fruits were studied. MnTF was rich in anthocyanins (11.3 mg/g and flavonols (0.7 mg/g identified by ultra-performance liquid chromatography–tunable ultraviolet/mass single-quadrupole detection (UPLC–TUV/QDa. Comparatively, MmTF and MazTF had low flavonol contents and MazTF had no anthocyanins. MnTF showed significantly higher antinociceptive and antibacterial activities toward Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus than MmTF and MazTF. MnTF inhibited the expression of interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, phospho-p65 (p-p65 and phospho-IκBα (p-IκBα, and increased interleukin 10 (IL-10. Additionally, mice tests showed that cyanidin-3-O-glucoside (C3G, rutin (Ru and isoquercetin (IQ were the main active ingredients in the antinociceptive process. Stronger antinociceptive effect of MnTF was correlated with its high content of anthocyanins and flavonols and its inhibitory effects on proinflammatory cytokines, iNOS and nuclear factor-κB (NF-κB pathway-related proteins.
Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

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Barbosa, A.L.R.; Pinheiro, C.A.; Oliveira, G.J.; Torres, J.N.L.; Moraes, M.O.; Ribeiro, R.A.; Vale, M.L.; Souza, M.H.L.P.

2012-01-01

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K + ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K + ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E 2 - (PGE 2 , 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE 2 ) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE 2 ) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE 2 ; 8 µg/paw) and the ATP-sensitive K + channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE 2 ; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels
Involvement of Opioid System, TRPM8, and ASIC Receptors in Antinociceptive Effect of Arrabidaea brachypoda (DC) Bureau.

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Rodrigues, Vinícius Peixoto; Rocha, Cláudia Quintino da; Périco, Larissa Lucena; Santos, Raquel de Cássia Dos; Ohara, Rie; Nishijima, Catarine Massucato; Ferreira Queiroz, Emerson; Wolfender, Jean-Luc; Rocha, Lúcia Regina Machado da; Santos, Adair Roberto Soares; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

2017-11-02

Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1), TRPA1 (transient receptor potential ankyrin 1), TRPM8 (transient receptor potential melastatin 8), and ASIC (acid-sensing ion channel), as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg/kg) in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief.
Evaluation of Antinociceptive Activity of Aqueous Extract of Bark of Psidium Guajava in Albino Rats and Albino Mice

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Jayasree, T.; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-01-01

Background: Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. Aim: To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Materials and Methods: Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. Results: The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. Conclusion: AEPG antinociceptive activity involves activation of the peripheral and central mechanisms. PMID:25386462
Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory.

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Del-Vechio-Vieira, Glauciemar; Santos, Bruna C S; Alves, Maria Silvana; Araújo, Aílson L A; Yamamoto, Célia H; Pinto, Míriam A O; Kaplan, Maria Auxiliadora C; Sousa, Orlando V

2016-07-11

The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1-pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine.

4'-Acetamidochalcone Derivatives as Potential Antinociceptive Agents

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Valdir Cechinel-Filho

2007-04-01

Full Text Available Nine acetamidochalcones were synthesized and evaluated as antinociceptive agents using the mice writhing test. Given intraperitoneally all the compounds were more effective than the two reference analgesic drugs (acetylsalicylic acid and acetaminophen used for comparison. N-{4-[(2E-3-(4-nitrophenylprop-2-enoyl]phenyl}acetamide (6 was the most effective compound and was therefore selected for more detailed studies. It caused dose-related inhibition in the writhing test, being about 32 to 34-fold more potent than the standard drugs. It was also effective in the second phase of the formalin test and the capsaicin test. These acetamidochalcones, especially compound 6, might be further used as models to obtain new and more potent analgesic drugs.
Antinociceptive activity of fruits extracts and "arrope" of Geoffroea decorticans (chañar).

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Reynoso, M A; Vera, N; Aristimuño, M E; Daud, A; Sánchez Riera, A

2013-01-09

Geoffroea decorticans (chañar) fruits and their derivate product (arrope) have been traditionally used as food and a folk medicine for the treatment of a wide variety of diseases including bronchopulmonary disorders and to relieve dolorous process. In order to evaluate the pharmacology action of this plant, studies were performed of antinociceptive and antioxidant activities. The aqueous and ethanolic extracts and arrope of chañar were evaluated in various established pain models, including chemical nociception induced by subplantar formalin and intraperitoneal acetic acid and thermal nociception method, such as tail immersion test in rats. To examine the possible connection of the opioid receptor to the antinociceptive activity of extracts and arrope it was performed a combination test with naloxone, a non-selective opioid receptor antagonist. The aqueous extract and arrope (1000 mg/kg) caused an inhibition of the pain in formalin test in the first phase, similar to morphine and decrease in the second phase. In a combination test using naloxone, diminished analgesic activity of aqueous extract and arrope were observed, indicating that antinociceptive activity is connected with the opioid receptor. The aqueous extract and arrope, caused an inhibition of the writhing response induced by acetic acid. Central involvement in analgesic profile was confirmed by the tail immersion test, in which the aqueous extract and arrope showed a significant analgesic activity by increasing latency time. The aqueous extract showed higher antioxidant activity than the arrope, it may be due to the cooking process. This study has shown that the aqueous extract and arrope of Geoffroea decorticans (chañar) fruits, does possess significant antinociceptive effects. It is further concluded that aqueous extract with maximum inhibition of free radical is the most potent extract amount tested extracts. At the oral doses tested the aqueous extract and arrope were non-toxic. The present
Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models

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Apparecido N. Daniel

Full Text Available Eugenia caryophyllata, popular name "clove", is grown naturally in Indonesia and cultivated in many parts of the world, including Brazil. Clove is used in cooking, food processing, pharmacy; perfumery, cosmetics and the clove oil (eugenol have been used in folk medicine for manifold conditions include use in dental care, as an antiseptic and analgesic. The objective of this study was evaluated the anti-inflammatory and antinociceptive activity of eugenol used for dentistry purposes following oral administration in animal models in vivo. The anti-inflammatory activity of eugenol was evaluated by inflammatory exudates volume and leukocytes migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. The antinociceptive activity was evaluated using the acetic acid-induced writhing and hot-plate tests in mice. Eugenol (200 and 400 mg/kg reduced the volume of pleural exudates without changing the total blood leukocyte counts. At dose of 200 mg/kg, eugenol significantly inhibited carrageenan-induced edema, 2-4 h after injection of the flogistic agent. In the hot-plate test, eugenol administration (100 mg/kg showed unremarkable activity against the time-to-discomfort reaction, recorded as response latency, which is blocked by meperidine. Eugenol at doses of 50, 75 and 100 mg/kg had a significant antinociceptive effect in the test of acetic-acid-induced abdominal writhing, compared to the control animals. The data suggest that eugenol possesses anti-inflammatory and peripheral antinociceptive activities.
Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

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Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292
Anti-inflammatory and antinociceptive activities of Rhipicephalus microplus saliva

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D F Buccini

2018-01-01

Full Text Available Objective: To evaluate the antinociceptive and anti-inflammatory activities and the toxic effects of Rhipicephalus microplus saliva for elucidating the modulation mechanism between arthropod saliva and host. Methods: For saliva collection, engorged ticks were obtained from a controlled bovine infestation and collected by natural fall. The ticks were fixed and injected pilocarpine 0.2% for induction of salivation. Saliva was collected, lyophilized and stored at - 80 °C. Cytotoxic activity was assessed by the hemolysis method (25, 50, 100, 200 and 300 μ g/mL and MTT cell viability assay (2.5, 5, 10, 20 and 40 μ g/mL for 24, 48 and 72 h. Anti-inflammatory activity was evaluated using the method of neutrophil migration to the peritoneal cavity of mice at doses of 10, 15 and 20 mg/kg; antinociceptive activity was assessed using the acetic acid-induced writhing test, and formalin-induced paw-licking in mice at dose of 15 mg/kg. Results: Saliva did not cause erythrocytes hemolysis at any concentration tested, as well as did not decrease cell viability in the MTT assay. Saliva inhibited neutrophil migration by 87% and 73% at doses of 15 and 20 mg/kg, respectively. In the nociceptive tests, saliva presented analgesic activity of 69.96% in the abdominal writhing test, and of 84.41% in the formalin test. Conclusions: The study proves that Rhipicephalus microplus saliva has significant in vivo anti-inflammatory and antinociceptive activities. The data presented herein support the development of further studies to elucidate the active principles of Rhipicephalus microplus saliva and its mechanism of action and, in future, to develop novel anti-inflammatory and analgesic drugs.
Isovitexin as marker and bioactive compound in the antinociceptive activity of the Brazilian crude drug extracts of Echinodorus scaber and E. grandiflorus

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Claudia Lea Strada

Full Text Available Abstract Echinodorus scaber Rataj and Echinodorus grandiflorus (Cham. & Schltdl. Micheli, Alismataceae, are popularly used to relieve inflammatory complaints and as diuretic. A study on the antinociceptive effect and selected marker compounds in eleven extracts from different locations was undertaken and their antinociceptive effect was assessed. The fingerprints were compared by HPLC-DAD and the content of vitexin, isovitexin, isoorientin and vitexin-2-O-rhamnoside were determined. All samples presented antinociceptive activity reducing the writhes by 36.4-62.5% and 47.4-79.8% at 10 and 50 mg/kg, respectively; indomethacin (5 mg/kg reduced writhes by 82.6-90.1%. The content of the flavonoids C-glycosides, however, presented a strong variation. Isovitexin and isoorientin were found in all the samples, with content ranging from traces to 14.70 µg/mg and 2.12-84.27 µg/mg extract, respectively, while vitexin-2-O-rhamnoside occurred in quantifiable amounts only in 3 out of 11 samples ranging from 5.43 to 33.13 µg/mg extract; vitexin was not detected at all or detected in trace amounts. According to the fingerprints, the samples could be arranged in four main groups. All eleven extracts showed antinociceptive activity. Isovitexin was the only flavonoid present in all samples and can be regarded, acting in synergy with the other compounds or not, as the responsible for the antinociceptive activity. Therefore, isovitexin is a good choice as chemical marker when the antinociceptive activity of E. scaber and E. grandiflorus is investigated.
Antinociceptive and anti-inflammatory activity of hydroalcoholic extracts and fractions from Erythrina mulungu

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Mariana S. G. de Oliveira

2012-02-01

Full Text Available Erythrina mulungu Mart. ex Benth., Fabaceae, popularly known as mulungu, is used for the treatment of insomnia and disorders of the central nervous system. This study examined the antinociceptive effects of the hydroalcoholic extracts (HAE, the ethyl acetate and chloroformic fractions from E. mulungu in four experimental models of nociception using laboratory mice. The extracts and fractions were administered orally to mice at doses of 100 mg/kg. Inhibition of abdominal contractions were observed for all the extracts and fractions tested, as compared to controls. All extracts and fractions from E. mulungu reduced the nociception activity produced by formalin in the 2nd phase. In the hot plate test no significant effect was observed for any extract or fraction. In the peritonitis test induced by Zymosan, all of the tested extracts and the chloroformic fraction, except for the ethyl acetate phase, reduced cell migration of the peritoneal cavity. We concluded that E. mulungu shows antinociceptive effects, which are independent of the opioid system.
Antinociceptive and anti-inflammatory activity of hydroalcoholic extracts and fractions from Erythrina mulungu

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Mariana S. G. de Oliveira

2011-11-01

Full Text Available Erythrina mulungu Mart. ex Benth., Fabaceae, popularly known as mulungu, is used for the treatment of insomnia and disorders of the central nervous system. This study examined the antinociceptive effects of the hydroalcoholic extracts (HAE, the ethyl acetate and chloroformic fractions from E. mulungu in four experimental models of nociception using laboratory mice. The extracts and fractions were administered orally to mice at doses of 100 mg/kg. Inhibition of abdominal contractions were observed for all the extracts and fractions tested, as compared to controls. All extracts and fractions from E. mulungu reduced the nociception activity produced by formalin in the 2nd phase. In the hot plate test no significant effect was observed for any extract or fraction. In the peritonitis test induced by Zymosan, all of the tested extracts and the chloroformic fraction, except for the ethyl acetate phase, reduced cell migration of the peritoneal cavity. We concluded that E. mulungu shows antinociceptive effects, which are independent of the opioid system.
Strong and long-lasting antinociceptive and anti-inflammatory conjugate of naturally occurring oleanolic acid and aspirin

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Barbara Bednarczyk-Cwynar

2016-07-01

Full Text Available The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7 and aspirin in dioxane. Analgesic effect of OAO-ASA (8 for the range of doses 0.3 – 300.0 mg/kg (p.o. was performed in mice using a hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8 did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c. the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c. did not affect the antinociceptive effect of OAO-ASA (8, therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o. in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8 was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8 is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8 on TNF-α level
Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

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M. H. Mohd. Sani

2012-01-01

Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.
Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

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Carvalho-Costa, P.G.; Branco, L.G.S.; Leite-Panissi, C.R.A.

2014-01-01

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress
Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

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Carvalho-Costa, P.G. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Branco, L.G.S. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Leite-Panissi, C.R.A. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2014-09-19

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.
The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938

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Perez-Burgos, Azucena; Wang, Lu; McVey Neufeld, Karen-Anne; Mao, Yu-Kang; Ahmadzai, Mustafa; Janssen, Luke J; Stanisz, Andrew M; Bienenstock, John; Kunze, Wolfgang A

2015-01-01

Abstract Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin-evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin- and distension-evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin-evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited capsaicin-evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin-evoked excitability. The TRPV1 antagonist 6-iodonordihydrocapsaicin or the use of TRPV1 knock-out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties. Key points Certain probiotic bacteria have been shown to reduce distension
Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents.

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Joyce Alencar Santos

Full Text Available This study investigated the antidepressant and antinociceptive effects of ethanolic extract (SLEE and pure fruticuline A obtained from Salvia lachnostachys leaves on rats and mice.In this study, SLEE (100 mg/kg, p.o. route was evaluated for its effects on spared nerve injury (SNI in rats. The animals were submitted to mechanical sensitivity, forced swim (FST and cold sensitivity tests 10 and 15 days after surgery. SLEE (100 mg/kg, p.o. and fruticuline A (3 mg/kg, p.o. were also evaluated with respect to nociceptive behavior induced by formalin. In addition, clonidine-induced depressive-like behavior was also analyzed.The oral administration of SLEE for up to 15 days and the subcutaneous injection of 10 mg/kg of ketamine (positive control significantly inhibited SNI-induced mechanical hyperalgesia and decreased immobility in the FST. On the 15th day of oral treatment, SLEE prevented the SNI-induced increase in cold sensitivity. In the formalin test, SLEE and fruticuline A significantly reduced the frequency of paw licking during the first and second phases and decreased the formation of edema. In locomotor analysis (open field test without clonidine treatment, SLEE and fruticuline A did not alter the response. SLEE and fruticuline A significantly attenuated clonidine-induced suppression of spontaneous locomotor activity (squares invaded and licking and emotionality (grooming and freezing compared with controls, similar to the naive group.SLEE exhibits antihyperalgesic, antidepressant, and antinociceptive effects, and fruticuline A appears to be at least partly responsible for the effects of SLEE. Together, these results demonstrate the antidepressive effects of SLEE and fruticuline A and indicate that both derivatives obtained from S. lachnostachys act against spontaneous neuropathic pain.
Participation of endogenous opioids in the antinociception induced by resistance exercise in rats

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G.S. Galdino

2010-09-01

Full Text Available Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group: untrained rats (control group; an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group; rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group, and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group. The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37%, P < 0.05 in the nociceptive threshold was produced immediately after exercise, decreasing to 15% after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.
Involvement of Opioid System, TRPM8, and ASIC Receptors in Antinociceptive Effect of Arrabidaea brachypoda (DC Bureau

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Vinícius Peixoto Rodrigues

2017-11-01

Full Text Available Arrabidaea brachypoda (DC Bureau is a medicinal plant found in Brazil. Known as “cipó-una”, it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10–100 mg/kg in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1, TRPA1 (transient receptor potential ankyrin 1, TRPM8 (transient receptor potential melastatin 8, and ASIC (acid-sensing ion channel, as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg/kg in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief.
Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

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Reis, Silvio Leandro Goncalves Bomfim; Almeida, Valderes Moraes de; Almeida, Gleybson Correia de; Boaviagem, Karinna Moura; Mendes, Charles Christophe du Barriere; Faria, Antonio Rodolfo de; Goes, Alexandre Jose da Silva; Magalhaes, Laudelina Rodrigues; Silva, Teresinha Goncalves da

2011-01-01

New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test. (author)
Antinociception induced by rosuvastatin in murine neuropathic pain.

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Miranda, Hugo F; Sierralta, Fernando; Aranda, Nicolas; Poblete, Paula; Castillo, Rodrigo L; Noriega, Viviana; Prieto, Juan Carlos

2018-06-01

Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated. A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

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Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

2014-01-01

Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueou...
The synergistic antinociceptive effect of lornoxicam in combination with tramadol

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Amela Saračević

2013-12-01

Full Text Available Introduction: One of the most important priorities in therapy is pain control. Therefore, many different groups of drugs are being used for this purpose, primarily opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs. Opioid analgesic tramadol, by binding to specific receptors, modulates the perception and response to painful stimuli and inhibits transmitting and further processing of pain impulses. Lornoxicam, which belongs to the oxicam class of NSAIDs, is a non-selective cyclooxygenase inhibitor with strong analgesic and anti-inflammatory effects, and better tolerance profile. Preliminary research, which requires further verification, suggests that lornoxicam may be a better alternative or adjunctive therapy to opioid analgesics in the treatment of moderate to severe pain. The aim of this study was to investigate antinociceptive effects of lornoxicam, as well as the combination of lornoxicam with tramadol.Methods: Analgesic effect of combination of lornoxicam and tramadol or lornoxicam applied alone was examined on female albino mice, using a hot plate method. Measurements were made 30, 60, 90 and 120 minutes after intraperitoneal and subcutaneous administration, in dose of 10 mg/kg.Results: Combination of lornoxicam and tramadol, applied intraperitoneally, increases the threshold of sensitivity to painful stimuli, which was not the case with subcutaneous administration.Conclusions: Lornoxicam significantly increases analgesic effect when applied intraperitoneally in combination with tramadol. On the other hand, lornoxicam in combination with tramadol, did not increase the threshold of sensitivity to painful stimuli with significant difference, after subcutaneous administration

Potentiation of oxycodone antinociception in mice by agmatine and BMS182874 via an imidazoline I2 receptor-mediated mechanism.

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Bhalla, Shaifali; Ali, Izna; Lee, Hyaera; Andurkar, Shridhar V; Gulati, Anil

2013-01-01

The potentiation of oxycodone antinociception by BMS182874 (endothelin-A (ET(A)) receptor antagonist) and agmatine (imidazoline receptor/α(2)-adrenoceptor agonist) is well-documented. It is also known that imidazoline receptors but not α(2)-adrenoceptors are involved in potentiation of oxycodone antinociception by agmatine and BMS182874 in mice. However, the involvement of specific imidazoline receptor subtypes (I(1), I(2), or both) in this interaction is not clearly understood. The present study was conducted to determine the involvement of imidazoline I(1) and I(2) receptors in agmatine- and BMS182874-induced potentiation of oxycodone antinociception in mice. Antinociceptive (tail flick and hot-plate) latencies were determined in male Swiss Webster mice treated with oxycodone, agmatine, BMS182874, and combined administration of oxycodone with agmatine or BMS182874. Efaroxan (imidazoline I(1) receptor antagonist) and BU224 (imidazoline I(2) receptor antagonist) were used to determine the involvement of I(1) and I(2) imidazoline receptors, respectively. Oxycodone produced significant antinociceptive response in mice which was not affected by efaroxan but was blocked by BU224. Agmatine-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. Similarly, BMS182874-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. This is the first report demonstrating that BMS182874- or agmatine-induced enhancement of oxycodone antinociception is blocked by BU224 but not by efaroxan. We conclude that imidazoline I(2) receptors but not imidazoline I(1) receptors are involved in BMS182874- and agmatine-induced potentiation of oxycodone antinociception in mice. Copyright © 2012 Elsevier Inc. All rights reserved.
Anti-inflammatory and anti-nociceptive activities of methanol extract from aerial part of Phlomis younghusbandii Mukerjee.

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Qiu-Shi Wang

Full Text Available This study was designed to investigate the anti-inflammatory and anti-nociceptive activity of the methanol extract from the aerial part of Phlomis younghusbandii (MEAP and to explore the possible related mechanisms. Anti-inflammatory effects of MEAP were evaluated by using the ear edema test induced by dimethylbenzene and vascular permeability test induced by acetic acid. Anti-nociceptive activities of MEAP were evaluated by the chemical nociception in models of acetic acid-induced writhing and formalin-induced hind paw licking, and by the thermal nociception in hot plate tests. Mechanisms of MEAP activities also were explored by evaluating expression levels of TNF-α, IL-6 and iNOS induced by LPS using real-time fluorogenic PCR and expression of COX-2 using Western blotting and an open-field test. The results indicated that the MEAP administered orally could significantly decrease ear edema induced by dimethylbenzene and increase vascular permeability induced by acetic acid. Additionally, the nociceptions induced by acetic acid and formalin were significantly inhibited. The anti-nociceptive effect could not be decreased by naloxone in the formalin test, and MEAP did not affect the normal autonomic activities of mice. Expression levels of pro-inflammatory cytokines (TNF-α, IL-6, iNOS induced by LPS were decreased obviously by treatment with MEAP. Furthermore, COX-2 expression in the spinal dorsal horns of the pain model mice induced by formalin was significantly down-regulated by MEAP. In conclusion, MEAP has significant anti-inflammatory and antinociceptive activities, and the mechanisms may be related to the down-regulated expression of TNF-α, IL-6, iNOS and COX-2.
"Interaction of different doses of Aspartame with Morphine-induced antinociception in the presence of MK-801, a NMDA antagonist "

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Abdollahi M

2002-07-01

Full Text Available This study was designed to investigate the relative role of sweetness and comparative effects of different taste sensation of the non - caloric sweetener , aspartame on pain and its interaction with MK - 80] as a non - selective MMDA antagonist by formalin - test in mice. The formalin - test was chosen because it measures the response to a long - lasting nociceptive stimulus and closely resembles to the clinical pain. Morphine induced a dose dependent antinociception in the early and late phases of formalin test. Twelve days pretreatment of animals by aspartame ( 0.08% , 0.16% , 0.32% significantly potentiated morphine - induced (1.5-9 mg/kg analgesia in the early phase but significantly antagonized its analgesic effect in the late phase, dose dependently. Aspartame (0.16% alone showed a reduction in pain response . Naloxone (0.4 mg/kg significantly antagonized the antinociceptive effect of morphine in the presence of aspartame (0-0.32% in the early phase. Increasing the dose of aspartame decreased effects of naloxone. MK-801 (0.1 mg/kg as an N- Methyl - D - Aspartate (NMDA antagonist significantly potentiated the effect of aspartame on morphine - induced antinociception in the early phase. In the late phase, naloxone (0.4 mg/kg increased pain response but MK- 801 (0.1 mg/kg induced anti-inflammatory effect significantly. Treatment of animals with MK- 801 alone, significantly induced analgesia in both phases of formalin - test. This effect was potentiated with aspartame dose - dependently. Possible interaction of aspartame with NMDA receptors and its role to facilitate endogenous opioid system are proposed mechanisms of aspartame in modulating morphine - induced antinociception. Furthermore, the resulting association between morphine and aspartame chronic consumption may be explained as an interactive action rather than simple dose combination of both drugs.
Antinociceptive and Anti-Inflammatory Activities of the Sesame Oil and Sesamin

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Érika Maria Henriques Monteiro

2014-05-01

Full Text Available Sesame oil is widely consumed as nutritious food, cooking oil, and in pharmaceuticals and food. In this study, the antinociceptive and anti-inflammatory properties of the sesame oil and sesamin were investigated. The sesame oil and sesamin reduced the number of abdominal contortions at the doses 100, 200, or 400 mg/kg. The first and second phases of the time paw licking were inhibited by sesame oil and sesamin (100, 200, or 400 mg/kg. After 90 min of treatment, sesame oil and sesamin increased the reaction time on a hot plate (200 or 400 mg/kg. Considering the tail-immersion assay, the sesame oil and sesamin produced significant effect after 60 min at the doses of 100, 200, or 400 mg/kg. After 4 h of application of the carrageenan, the sesame oil and sesamin were effective against the paw edema. The exudate volume and leucocyte migration were also reduced by sesame oil and sesamin. These results suggest that sesamin is one of the active compounds found in sesame oil and justify the antinociceptive and anti-inflammatory properties of this product.
Antioxidant, anti-inflammatory and antinociceptive activities of ...

African Journals Online (AJOL)

Background of study: Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Aim: The study evaluated the in vitro antioxidant, antinociceptive, and anti-inflammatory activities of the methanolic extract of Justicia secunda Vahl leaf. Methods: The acute ...
Antinociceptive and antipyretic activities of Amaranthus viridis Linn. in different experimental models

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Kumar Ashok B.S.

2010-01-01

Full Text Available The methanolic extract of the whole plant extract of Amaranthus viridis L (MEAV was screened for antinociceptive activity using the acetic acid writhing test, hot plate test and tail immersion test in mice and for antipyretic activity using the yeast-induced pyrexia method in rats, at doses of 200 and 400 mg/kg body weight. Significant (p<0.01 dose-dependent antinociceptive and antipyretic properties were observed with 200 and 400 mg/kg.
Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

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L.H. Santos

2004-08-01

Full Text Available We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg in male Wistar rats (180-300 g, N = 6 and compared it to free diclofenac (5 or 10 mg/kg and to the combination of diclofenac (5 or 10 mg/kg and zinc acetate (1.68 or 3.5 mg/kg. The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18ºC for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.
Evaluation of Antinociceptive Activity of Ethanol Extract of Leaves of Adenanthera pavonina

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Md. Moniruzzaman

2015-01-01

Full Text Available Adenanthera pavonina is a deciduous tree commonly used in the traditional medicine to treat inflammation and rheumatism. The aim of this study was to evaluate the antinociceptive activity of ethanol extract of leaves of A. pavonina (EEAP. EEAP was investigated using various nociceptive models induced thermally or chemically in mice including hot plate and tail immersion test, acetic acid-induced writhing, and glutamate- and formalin-induced licking tests at the doses of 50, 100, and 200 mg/kg body weight (p.o.. In addition, to assess the possible mechanisms, involvement of opioid system was verified using naloxone (2 mg/kg and cyclic guanosine monophosphate (cGMP signaling pathway by methylene blue (MB; 20 mg/kg. The results have demonstrated that EEAP produced a significant and dose-dependent increment in the hot plate latency and tail withdrawal time. It also reduced the number of abdominal constrictions and paw lickings induced by acetic acid and glutamate respectively. EEAP inhibited the nociceptive responses in both phases of formalin test. Besides, the reversal effects of naloxone indicated the association of opioid receptors on the exertion of EEAP action centrally. Moreover, the enhancement of writhing inhibitory activity by MB suggests the possible involvement of cGMP pathway in EEAP-mediated antinociception. These results prove the antinociceptive activity of the leaves of A. pavonina and support the traditional use of this plant.
Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

2015-02-21

There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 μg/kg) and acepromazine (50 μg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 μg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 μg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 μg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 μg/kg detomidine, and AUC60-120 for 10 μg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 μg/kg than for 17 and 20 μg/kg detomidine. MNT AUC60-120 values were larger for 20 μg/kg detomidine than for saline, 10 μg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia. British Veterinary Association.
Endogenous opioid peptide-mediated neurotransmission in central and pericentral nuclei of the inferior colliculus recruits μ1-opioid receptor to modulate post-ictal antinociception.

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Felippotti, Tatiana Tocchini; de Freitas, Renato Leonardo; Coimbra, Norberto Cysne

2012-02-01

The aim of the present work was to investigate the involvement of the μ1-endogenous opioid peptide receptor-mediated system in post-ictal antinociception. Antinociceptive responses were determined by the tail-flick test after pre-treatment with the selective μ1-opioid receptor antagonist naloxonazine, peripherally or centrally administered at different doses. Peripheral subchronic (24 h) pre-treatment with naloxonazine antagonised the antinociception elicited by tonic-clonic seizures. Acute (10 min) pre-treatment, however, did not have the same effect. In addition, microinjections of naloxonazine into the central, dorsal cortical and external cortical nuclei of the inferior colliculus antagonised tonic-clonic seizure-induced antinociception. Neither acute (10-min) peripheral pre-treatment with naloxonazine nor subchronic intramesencephalic blockade of μ1-opioid receptors resulted in consistent statistically significant differences in the severity of tonic-clonic seizures shown by Racine's index (1972), although the intracollicular specific antagonism of μ1-opioid receptor decreased the duration of seizures. μ1-Opioid receptors and the inferior colliculus have been implicated in several endogenous opioid peptide-mediated responses such as antinociception and convulsion. The present findings suggest the involvement of μ1-opiate receptors of central and pericentral nuclei of the inferior colliculus in the modulation of tonic-clonic seizures and in the organisation of post-ictal antinociception. Copyright © 2011 Elsevier Ltd. All rights reserved.
Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata

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Noureddine Bribi

2015-01-01

Full Text Available Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2 in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis.
Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice.

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Taher, Yousef A; Samud, Awatef M; El-Taher, Fathy E; ben-Hussin, Ghazala; Elmezogi, Jamal S; Al-Mehdawi, Badryia F; Salem, Hanan A

2015-01-01

Clove oil of Eugenia caryophyllata (Myrtaceae) is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache. The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice. Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer's-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p.) at a dose of 33 mg/kg body weight and the effects were compared with reference drugs. In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acid-induced writhing movements by a maximum of 87.7% (pscreening of the oil showed the presence of eugenol. The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine.
Antinociceptive effect in mice of a hydroalcoholic extract of Neurolaena lobata (L.) R. Br. and its organic fractions.

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Gracioso, J S; Paulo, M Q; Hiruma Lima, C A; Souza Brito, A R

1998-12-01

An infusion of the aerial parts of Neurolaena lobata (L.) R. Br. (Compositae-Asteraceae) is used in Caribbean folk medicine to treat several kinds of pain. In this investigation we studied the acute oral toxicity of the hydroalcoholic extract of the plant and the antinociceptive effect of the extract and of its hexane- and chloroform-partitioned fractions, given orally, in nociception and inflammatory models in mice. No signs of toxicity were observed for oral doses up to 5000 mg kg(-1) in mice. Morphine hydrochloride (100 mg kg(-1)), dipyrone sodium (200 mg kg(-1)), the hydroalcoholic extract (1000 mg kg(-1)), and its chloroform- and hexane-partitioned fractions (100 mg kg(-1)) significantly inhibited acetic acid-induced abdominal constriction in mice (100, 95, 47, 62 and 60% inhibition, respectively when compared with the negative control). In the hot-plate test in mice, morphine hydrochloride, the chloroform- and hexane-partitioned fractions, but not the hydroalcoholic extract, resulted in a significant latency increase in all observation times. In the acetic acid-induced abdominal constriction in mice, pretreatment of the animals with naloxone significantly reversed the analgesic effect of morphine, but not that of the hydroalcoholic extract or of its hexane- and chloroform-partitioned fractions. Finally, administration of the hexane- and chloroform-partitioned fractions (100 mg kg(-1)) had a significant anti-oedematogenic effect on carrageenan-induced oedema in mice. These data show that the hydroalcoholic extract of N. lobata and, in particular, its partitioned fractions have significant analgesic properties when assessed through these pain models. Their antinociceptive effect might be the result of interference with the inflammatory process.
Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception.

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de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Falconi-Sobrinho, Luiz Luciano; Biagioni, Audrey Franceschi; Almada, Rafael Carvalho; Dos Anjos-Garcia, Tayllon; Bazaglia-de-Sousa, Guilherme; Khan, Asmat Ullah; Coimbra, Norberto Cysne

2018-05-12

Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0 μg/0.2 μL) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0 min) and subsequently at 10-min intervals until 130 min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130 min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity. Copyright © 2018 Elsevier Inc. All rights reserved.
Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

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Eliezer J. Barreiro

2012-11-01

Full Text Available In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1, a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637 and 14g (LASSBio-1639 were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2 at concentrations of 10 mM.
Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

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de Miranda, Amanda Silva; Bispo Júnior, Walfrido; da Silva, Yolanda Karla Cupertino; Alexandre-Moreira, Magna Suzana; Castro, Rosane de Paula; Sabino, José Ricardo; Lião, Luciano Morais; Lima, Lídia Moreira; Barreiro, Eliezer J

2012-11-28

In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.
Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

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Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

2007-07-01

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.
Sedative and mechanical antinociceptive effects of four dosages of romifidine administered intravenously to donkeys.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

2017-06-01

Although romifidine is commonly used to provide sedation and analgesia for the facilitation of clinical procedures in donkeys, limited scientific information is available for this drug in this species. This randomized, controlled, crossover, Latin-square, blinded study compared the sedative and antinociceptive effects of four dosages of romifidine (40, 60, 80, and 100μg/kg IV; R40, R60, R80, and R100, respectively), acepromazine (0.1mg/kg IV; ACE) and saline (0.9%, 5mL IV) by assigning sedation scores (SS) and measuring head heights above ground (HHAG) and mechanical nociceptive thresholds (MNT) in donkeys. Areas under the curve (AUC) from 0 to 30, 30-60, 60-120, and 120-180min after administration were computed for SS, HHAG, and MNT and compared among treatments. Romifidine and ACE, but not saline, induced clinical signs of sedation. SS-AUC 0-30 for R60, R80 and R100, and SS-AUC 30-60 for R100 were higher than corresponding values for saline. HHAG-AUC 30-60 for R40 and R80, and HHAG-AUC 60-120 for R40, R60, R80 and R100 were smaller than for saline. HHAG-AUC 60-120 for R100 were also smaller than those for ACE. Romifidine, but not saline or ACE, increased MNT. MNT-AUC 0-30 and MNT-AUC 30-60 for R40, R60, R80 and R100, and MNT-AUC 60-120 for R80 and R100 were higher than corresponding values for saline and ACE. MNT-AUC 60-120 for R100 were higher than for all other romifidine treatments. In donkeys, the degree of sedation was similar for the four dosages of romifidine, but antinociception was dose-dependent. Copyright © 2017 Elsevier Ltd. All rights reserved.
A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses.

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Moens, Yves; Lanz, Francisca; Doherr, Marcus G; Schatzmann, Urs

2003-07-01

To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Randomized, placebo-controlled, blinded cross-over study. Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years. Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point. The three alpha2-agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean +/- SD) for detomidine at 15 minutes (from control 5.8 +/- 0.9 to 23.3 +/- 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 +/- 1.1 to 18.8 +/- 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 +/- 0.9 to 18.7 +/- 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 +/- 0.2 to 6.2 +/- 0.5 N, p = 0.00076) and 30 minutes (from 3.2 +/- 0.7 to 5.7 +/- 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 +/- 0.2 to 5.6 +/- 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 +/- 1.3 times
Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

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de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Franceschi; Falconi-Sobrinho, Luiz Luciano; Dos Anjos-Garcia, Tayllon; Coimbra, Norberto Cysne

2016-10-01

Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain.

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Miranda, Hugo F; Noriega, Viviana; Prieto, Juan Carlos; Zanetta, Pilar; Castillo, Rodrigo; Aranda, Nicolás; Sierralta, Fernando

2016-08-01

Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1β concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1β induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1β. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1β, in a model of mice PSNL which could be due to an inhibition of glial function. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Antinociceptive action and redox properties of citronellal, an essential oil present in lemongrass.

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Quintans-Júnior, Lucindo; da Rocha, Ricardo Fagundes; Caregnato, Fernanda Freitas; Moreira, José Claudio Fonseca; da Silva, Francilene Amaral; Araújo, Adriano Antunes de Souza; dos Santos, João Paulo Almeida; Melo, Mônica Santos; de Sousa, Damião Pergentino; Bonjardim, Leonardo Rigoldi; Gelain, Daniel Pens

2011-06-01

Citronellal (CT) is a monoterpenoid and the major constituent of the mixture of terpenoids that give the citronella oil its lemon scent. Citronella oil is widely used around the world for various purposes and is mainly obtained from plants of the Cymbopogon genus, which are known as "lemongrass." Considering these plants have been used worldwide for various medicinal purposes, the interest of researchers to understand the biological activities of monoterpenoids related to the Cymbopogon genus has been increasing. In the present work, we investigated the antinociceptive action and the redox properties of CT. Our results indicate that intraperitoneal injection of CT was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CT also evoked antinociceptive response in the capsaicin and glutamate tests. The total radical-trapping antioxidant parameter and total antioxidant reactivity assays indicate that CT at doses of 0.1 and 1 mg/mL exerts a significant antioxidant activity, which is probably related to its ability to scavenge superoxide and nitric oxide, but not H(2)O(2) or hydroxyl radicals, as evaluated separately by specific in vitro tests. These results show for the first time the antinociceptive potential of CT and indicate that the antioxidant properties of this compound may rely on its mechanism of biological actions because CT-containing natural products are used to treat various diseases related to oxidative stress and reactive species.
Antinociceptive and anti-inflammatory properties of methanol fruit ...

African Journals Online (AJOL)

Purpose: To investigate the anti-inflammatory and antinociceptive properties of crude methanol fruit extract of Quercus incana (QI), as well as its acute toxicity and phytochemical profile. Methods: Two animal models were used: Wistar rats for carrageenan-induced paw inflammation and Swiss albino mice for acetic ...
Mediation by the serotonergic system of U-50,488H-induced antinociception and tolerance

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Ho, Begonia Yeeman.

1989-01-01

The antinociceptive action of U-50,488H, a selective {kappa}-opioid receptor agonist, was attenuated by serotonergic but not by noradrenergic receptor antagonists. Intracerebroventricularly (i.c.v.) administered U-50,488H was antagonized by more than two fold by i.c.v. administered pindolol, methysergide, mianserin, ketanserin, pirenperone or ICS-205,930. A similar degree of antagonism of U-50,488H (i.c.v.) was found after intrathecal (i.t.) treatments with pindolol, methysergide or ICS-205,930 but not with mianserin, ketanserin or pirenperone. When U-50,488H and the antagonists were both given i.t., its antinociceptive action was attenuated by pindolol or methysergide, potentiated by mianserin, ketanserin or pirenperone and not affected by ICS-205,930. The release of serotonin was further studied directly by using a superfusion system. A naloxone reversible, concentration- and Ca{sup 2+}- dependent enhancement of release of ({sup 3}H)serotonin by U-50,488H was observed in spinal and brain tissues. Tolerance to the antinociceptive action of U-50,488H was induced in mice using slow release preparations of U-50,488H. Serotonergic receptor antagonists (pindolol or ketanserin) were co-administered with U-50,488H to test for their effects on the development of tolerance to U-50,488H.
Ventrolateral periaqueductal gray lesion attenuates nociception but does not change anxiety-like indices or fear-induced antinociception in mice.

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Mendes-Gomes, Joyce; Amaral, Vanessa Cristiane Santana; Nunes-de-Souza, Ricardo Luiz

2011-06-01

The exposure of rodents to an open elevated plus-maze (oEPM: four open arms raised from the floor) elicits naloxone-insensitive antinociception. Midazolam infusion into the dorsal portion of the periaqueductal gray (dPAG), a structure of the descending inhibitory system of pain, failed to alter oEPM-induced antinociception. Chemical lesion of dorsomedial and dorsolateral PAG attenuated defensive behavior in the standard EPM (sEPM), an animal model of anxiety, but failed to change oEPM-induced antinociception. The present study investigated the effects of bilateral lesion, with the injection of NMDA (N-methyl-D-aspartic acid), of the ventrolateral column of PAG (vlPAG) (i) on nociceptive response induced by 2.5% formalin injected into the right hind paw (nociception test) in mice exposed to the enclosed EPM (eEPM: four enclosed arms - a non-aversive situation) or to the oEPM and (ii) on anxiety indices in mice exposed to the sEPM without prior formalin injection. Results showed that oEPM-induced antinociception was not altered by lesion of vlPAG. Nevertheless, the lesion reduced the nociceptive response in mice exposed to the eEPM and increased general locomotor activity during the eEPM and oEPM exposure. Furthermore, vlPAG lesion did not alter anxiety-like indices in mice exposed to the sEPM. The results suggest that vlPAG does not play a role in oEPM-induced antinociception or in defensive reactions assessed in the sEPM. Moreover, vlPAG inactivation induces pain inhibition in mice not exposed to an aversive situation and seems to increase general activity. Copyright © 2011 Elsevier B.V. All rights reserved.
Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats.

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Haghparast, Abbas; Ordikhani-Seyedlar, Mehdi; Ziaei, Maryam

2008-06-27

Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (Peffects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.
Antinociceptive and anti-arthritic properties of hydroethanolic leaf ...

African Journals Online (AJOL)

olayemitoyin

The present study sought to investigate the antinociceptive and anti- arthritic properties of .... Experimentation Committee of the College of. Medicine ... Acute toxicity test: Female albino mice were fasted for 12 h before .... In another series of experiment, the ..... in the mechanisms underlying pain perception based on the fact ...
Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models.

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Boakye-Gyasi, Eric; Henneh, Isaac Tabiri; Abotsi, Wonder Kofi Mensah; Ameyaw, Elvis Ofori; Woode, Eric

2017-04-26

Despite substantial advances in pain research and treatment, millions of people continue to suffer from pain and this has been attributed mainly to the unavailability of effective and safer analgesics. The use of plants as medicines is still widespread and plants constitute a large source of novel phytocompounds that might become leads for the discovery of newer, effective and safer alternatives. Various parts of Ziziphus abyssinica have been used in folk medicine in several African countries as painkillers. However, there is no report on the possible anti-nociceptive effects of this plant especially the leaves, hence the need for this current study. The possible anti-nociceptive activity of hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) was assessed in rodents using chemical (acetic acid, formalin and glutamate), thermal (tail-immersion test) and mechanical/inflammatory (carrageenan) models of nociception. EthE (30-300 mg/kg, p.o.) dose-dependently and significantly inhibited chemical-induced nociception with a maximum inhibition of 86.29 ± 2.27%, 76.34 ± 5.67%, 84.97 ± 5.35%, and 82.81 ± 5.97% respectively for acetic acid, formalin (phase 1), formalin (phase 2) and glutamate tests at its highest dose. EthE also dose-dependently and significantly increased reaction times in both tail-immersion and carrageenan-induced hypernociceptive tests. The activities of the extract in the various models were comparable with the effect of morphine hydrochloride and diclofenac sodium used as standard analgesic drugs. Oral administration of hydro-ethanolic leaf extract of Ziziphus abyssinica ameliorates nocifensive behaviours associated with chemical-, thermal- and mechanical/inflammatory - induced nociceptive pain.
In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

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Mahdi, Harith Jameel; Khan, Nurzalina Abdul Karim; Asmawi, Mohd Zaini Bin; Mahmud, Roziahanim; A/L Murugaiyah, Vikneswaran

2018-03-01

The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.
Antinociceptive and anti-inflammatory kaempferol glycosides from Sedum dendroideum.

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De Melo, Giany O; Malvar, David do C; Vanderlinde, Frederico A; Rocha, Fabio F; Pires, Priscila Andrade; Costa, Elson A; de Matos, Lécia G; Kaiser, Carlos R; Costa, Sônia S

2009-07-15

To identify the compounds responsible for the antinociceptive and anti-inflammatory effects previously described for Sedum dendroideum, through bioassay-guided fractionation procedures. Antinociceptive activity was evaluated through mouse acetic acid-induced writhing model. The anti-inflammatory activity was assessed through croton oil-induced mouse ear oedema and carrageenan-induced peritonitis. The Sedum dendroideum juice afforded seven known flavonoids identified with basis on NMR data. The oral administration of the major kaempferol glycosides kaempferitrin [1] (17.29 micromol/kg), kaempferol 3-O-beta-glucopyranoside-7-O-alpha-rhamnopyranoside [2] (16.82 micromol/kg), kaempferol 3-O-neohesperidoside-7-O-alpha-rhamnopyranoside [3] (13.50 micromol/kg) or alpha-rhamnoisorobin [5] (23.13 micromol/kg) inhibited by 47.3%, 25.7%, 60.2% and 58.0%, respectively, the acetic acid-induced nociception (indomethacin: 27.95 micromol/kg, p.o.; 68.9%). Flavonoids 1, 2, 3 or 5, at the same doses, reduced by 39.5%, 46.5%, 35.6% and 33.3%, respectively, the croton oil-induced oedema (dexamethasone: 5.09 micromol/kg, s.c.; 83.7%) and impaired leukocyte migration by 42.9%, 46.3%, 50.4% and 49.6%, respectively (dexamethasone: 5.09 micromol/kg, s.c.; 66.1%). Our findings show that the major kaempferol glycosides may account for the renowned medicinal use of Sedum dendroideum against pain and inflammatory troubles.
Study of antinociceptive and anti-inflammatory activities of certain Iranian medicinal plants

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Fariba Sharififar

2012-02-01

Methods: The antinociceptive and anti-inflammatory activity of methanol extracts of tested plants were evaluated using hot-plate and carrageenan-induced edema methods respectively. The plant extracts were studied by i.p administration at three doses of 100, 200 and 400mg/kg. Results: In the hot-plate test, the extracts of T. foeunm-graecum (100 mg/kg and Z. majdae (200 and 400m g/kg significantly increased the tolerance to pain in female albino mice in comparison to control. The administration of T. foenum-graecum at doses of 100 and 200mg/kg and V. tricolor (400mg/kg significantly reduced the paw edema in male rat which measured in all the times of observation after carrageenan administration in comparison to control and reference (Ibuprofen, 400mg/kg. Conclusions: The present work comparatively demonstrated considerable antinociceptive and anti inflammatory effect of all of the tested plants especially T. foeunm-graecum. The results here confirm traditional uses of T. foeunm-graecum both as analgesic or anti inflammatory agents. [J Intercult Ethnopharmacol 2012; 1(1.000: 19-24
Antinociceptive properties of the aqueous and methanol extracts of the stem bark of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) in mice.

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Bomba, Francis Desire Tatsinkou; Wandji, Bibiane Aimee; Piegang, Basile Nganmegne; Awouafack, Maurice Ducret; Sriram, Dharmarajan; Yogeeswari, Perumal; Kamanyi, Albert; Nguelefack, Telesphore Benoit

2015-11-04

Aqueous maceration from the stem barks of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is taken orally in the central Africa for the management of various ailments, including pain. This work was carried out to evaluate in mice, the antinociceptive effects of the aqueous and methanol extracts of the stem bark of P. macrocarpus. The chemical composition of the aqueous and methanol extracts prepared as cold macerations was determined by high performance liquid chromatography coupled with mass spectrometry (LCMS). The antinociceptive effects of these extracts administered orally at the doses of 100, 200 and 400 mg/kg were evaluated using behavioral pain model induced by acetic acid, formalin, hot-plate, capsaicin and glutamate. The rotarod test was also performed at the same doses. The oral acute toxicity of both extracts was studied at the doses of 800, 1600, 3200 and 6400 mg/kg in mice. The LCMS analysis revealed the presence of ellagic acid as the major constituent in the methanol extract. Both extracts of P. macrocarpus significantly and dose dependently reduced the time and number of writhing induced by acetic acid. They also significantly inhibited the two phases of formalin-induced pain. These effects were significantly inhibited by a pretreatment with naloxone, except for the analgesic activity of the methanol extract at the earlier phase. In addition, nociception induced by hot plate, intraplantar injection of capsaicin or glutamate was significantly inhibited by both extracts. Acute toxicity test showed no sign of toxicity. These results demonstrate that aqueous and methanol extracts of P. macrocarpus are none toxic substances with good central and peripheral antinociceptive effects that are at least partially due to the presence of ellagic acid. These extracts may induce their antinociceptive effect by interfering with opioid, capsaicin and excitatory amino acid pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

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Deise Prehs Montrucchio

Full Text Available S-(+-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+-dicentrine (100 mg/kg reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C. Moreover, S-(+-dicentrine (100 mg/kg, p.o. was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+-dicentrine reduced the licking time (spontaneous nociception and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity, both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.
Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys.

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Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

2017-05-01

To assess and compare the sedative and antinociceptive effects of four dosages of dexmedetomidine in donkeys. Randomized, controlled, crossover, Latin-square, blinded study. Six healthy, castrated, adult, standard donkeys. Dexmedetomidine (2, 3, 4 and 5 μg kg -1 ; D2, D3, D4 and D5), acepromazine (0.1 mg kg -1 ) and saline were administered intravenously to each donkey and a 1 week interval was allowed between successive trials on each animal. Sedation scores (SS) and head heights above ground (HHAG) were used to assess sedation and mechanical nociceptive threshold (MNT) testing to assess antinociception over 120 minutes post-treatment. Areas under the curve (AUC) for 0-30, 30-60 and 60-120 minutes were computed to compare the effect of treatments. SS-AUC 0-30 values were larger for D4 and D5, and SS-AUC 30-60 values were larger for D5 than for saline. All dexmedetomidine treatments produced lower HHAG-AUC 0-30 and HHAG-AUC 30-60 values, and acepromazine produced lower HHAG AUC 60-120 values than did saline. For MNT, D3, D4 and D5 increased AUC 0-30 and AUC 30-60 values compared with saline and also AUC 0-30 values compared with D2 and acepromazine. Smaller MNT-AUC 30-60 values were obtained with D2 than with D4 and D5, with D3 than with D5, and with acepromazine than with D4 and D5. Dexmedetomidine induced sedation and dosage-dependent mechanical antinociception. Larger dexmedetomidine dose rates were required to induce antinociception than sedation. Furthermore, the antinociception induced by dexmedetomidine was of shorter duration than its sedation. For minor painful procedures on standing donkeys, D5 may be clinically useful to provide sedation and analgesia. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; KuKanich, Butch; Keuler, Nicholas S; Klauer, Julia M; Paul-Murphy, Joanne R

2011-06-01

To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis). 14 healthy adult Hispaniolan Amazon parrots of unknown sex. 3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration. Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively. Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.
Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf Extract of Trema Cannabina Lour

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Hira Arpona

2013-02-01

Full Text Available Purpose: The present study was designed to investigate the anti-nociceptive activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae in experimental animal models. Methods: The anti-nociceptive action was carried out against two types of noxious stimuli, thermal (hot plate and tail immersion tests and chemical (acetic acid-induced writhing in mice. Results: Phytochemical analysis of crude extract indicated the presence of reducing sugar, tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T. cannabina (500 mg/kg dose showed maximum time needed for the response against thermal stimuli (6.79±0.15 seconds which is comparable to diclofenac sodium (8.26±0.14 seconds in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. At the dose of 250 and 500 mg/kg body weight, the extract showed significantly and in a dose-dependent (p<0.001 reduction in acetic acid induced writhing in mice with a maximum effect of 47.56% reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07% at 25 mg/kg. Conclusion: The obtained results tend to suggest the Anti-nociceptive activity of ethanolic leaf extract of Trema cannabina and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain.
Role of neurotensin and opioid receptors in the cardiorespiratory effects of [Ile⁹]PK20, a novel antinociceptive chimeric peptide.

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Kaczyńska, Katarzyna; Szereda-Przestaszewska, Małgorzata; Kleczkowska, Patrycja; Lipkowski, Andrzej W

2014-10-15

Ile(9)PK20 is a novel hybrid of opioid-neurotensin peptides synthesized from the C-terminal hexapeptide of neurotensin and endomorphin-2 pharmacophore. This chimeric compound shows potent central and peripheral antinociceptive activity in experimental animals, however nothing is known about its influence on the respiratory and cardiovascular parameters. The present study was designed to determine the cardiorespiratory effects exerted by an intravenous injection (i.v.) of [Ile(9)]PK20. Share of the vagal afferentation and the contribution of NTS1 neurotensin and opioid receptors were tested. Intravenous injection of the hybrid at a dose of 100 μg/kg in the intact, anaesthetized rats provoked an increase in tidal volume preceded by a prompt short-lived decrease. Immediately after the end of injection brief acceleration of the respiratory rhythm appeared, and was ensued by the slowing down of breathing. Changes in respiration were concomitant with a bi-phasic response of the blood pressure: an immediate increase was followed by a sustained hypotension. Midcervical vagotomy eliminated the increase in tidal volume and respiratory rate responses. Antagonist of opioid receptors - naloxone hydrochloride eliminated only [Ile(9)]PK20-evoked decline in tidal volume response. Blockade of NTS1 receptors with an intravenous dose of SR 142,948, lessened the remaining cardiorespiratory effects. This study depicts that [Ile(9)]PK20 acting through neurotensin NTS1 receptors augments the tidal component of the breathing pattern and activates respiratory timing response through the vagal pathway. Blood pressure effects occur outside vagal afferentation and might result from activation of the central and peripheral vascular NTS1 receptors. In summary the respiratory effects of the hybrid appeared not to be profound, but they were accompanied with unfavourable prolonged hypotension. Copyright © 2014 Elsevier B.V. All rights reserved.
Antinociceptive and Anti-inflammatory Effects of a Lectin-Like Substance from Clitoria fairchildiana R. Howard Seeds

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Tatiane Santi-Gadelha

2012-03-01

Full Text Available Lectins are proteins that have the ability to bind specifically and reversibly to carbohydrates and glycoconjugates, without altering the structure of the glycosyl ligand. They are found in organisms such as viruses, plants and humans, and they have been shown to possess important biological activities. The objective of this study was to purify and characterize lectins in the seeds of Clitoria fairchildiana, as well as to verify their biological activities. The results indicated the presence of a lectin (CFAL in the glutelin acid protein fraction, which agglutinated native rabbit erythrocytes. CFAL was purified by column chromatography ion-exchange, DEAE-Sephacel, which was obtained from a peak of protein retained in the matrix by applying 0.5 M NaCl using the step-wise method. Electrophoretic analysis of this lectin in SDS-PAGE indicated a two band pattern protein molecular mass of approximately 100 and 116 kDa. CFAL proved to be unspecific to all carbohydrates/glycoconjugates in common use for the sugar inhibition test. This lectin showed no significant cytotoxicity to human red blood cells. It was observed that CFAL has anti-inflammatory activity in the paw edema induced by carrageenan model, in which a 64% diminution in edema was observed. Antinociceptive effects were observed for CFAL in the abdominal writhing test (induced by acetic acid, in which increasing doses of the lectin caused reduction in the number of contortions by up to 72%. It was concluded that the purified and characterized lectin from the seeds of Clitoria fairchildiana has anti-inflammatory and antinociceptive activity, and is not cytotoxic to human erythrocytes.
Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice.

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Ganguly, Amlan; Al Mahmud, Zobaer; Kumar Saha, Sajal; Abdur Rahman, S M

2016-08-01

Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p analgesic activity having 74.15 and 82.15% (p screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.
Assessments of thermal antinociceptive effects of butorphanol and human observer effect on quantitative evaluation of analgesia in green iguanas (Iguana iguana).

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Fleming, Gregory J; Robertson, Sheilah A

2012-10-01

To determine whether butorphanol induces thermal antinociception in green iguanas (Iguana iguana) and assess the human observer effect on quantitative evaluation of butorphanol-induced analgesia. 6 juvenile green iguanas. Skin temperature was recorded, and then a direct increasing heat stimulus was applied to the lateral aspect of the tail base of each iguana. Temperature of the stimulus at which the iguana responded (thermal threshold) was measured before and for 8 hours after IM injection of either butorphanol tartrate (1.0 mg/kg) or an equal volume of saline (0.9% NaCl) solution. Six experiments (butorphanol [n = 3] and saline solution [3]) were conducted with the observer in the iguanas' field of vision, and 11 experiments (butorphanol [n = 5] and saline solution [6]) were conducted with the observer hidden from their view. The interval between treatments or tests was ≥ 1 month. Temperature difference between thermal threshold and skin temperature when iguanas were administered saline solution did not differ from temperature difference when iguanas were administered butorphanol regardless of whether the observer was or was not visible. Temperature difference between thermal threshold and skin temperature was significantly lower when iguanas were tested without the observer in visual range, compared with the findings obtained when iguanas were tested with an observer in view, at multiple times after either treatment. Intramuscular administration of 1.0 mg of butorphanol/kg did not induce thermal antinociception in juvenile green iguanas. The visible presence of an observer appeared to influence the results of noxious stimulus testing in this reptile species.

Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.

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Wang, Chen; Zhou, Jiangrui; Wang, Shuowen; Ye, Mingliang; Jiang, Chunlei; Fan, Guorong; Zou, Hanfa

2010-06-04

This study investigated the mechanisms involved in the antinociceptive action induced by levo-tetrahydropalmatine (l-THP) in the formalin test by combined comparative and chemical proteomics. Rats were pretreated with l-THP by the oral route (40 mg/kg) 1 h before formalin injection. The antinociceptive effect of l-THP was shown in the first and second phases of the formalin test. To address the mechanisms by which l-THP inhibits formalin-induced nociception in rats, the combined comparative and chemical proteomics were applied. A novel high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS was applied to simultaneously evaluate the deregulated proteins involved in the response of l-THP treatment in formalin-induced pain rats. Thousands of proteins were identified, among which 17 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (Neurabin-1 and Calcium-dependent secretion activator 1) were randomly selected, and their expression levels were further confirmed by Western Blots. The results matched well with those of proteomics. In the present study, we also described the development and application of l-THP immobilized beads to bind the targets. Following incubation with cellular lysates, the proteome interacting with the fixed l-THP was identified. The results of comparative and chemical proteomics were quite complementary. Although the precise roles of these identified moleculars in l-THP-induced antinociception need further study, the combined results indicated that proteins associated with signal transduction, vesicular trafficking and neurotransmitter release, energy metabolism, and ion transport play important roles in l-THP-induced antinociception in the formalin test.
Relative contributions of norepinephrine and serotonin transporters to antinociceptive synergy between monoamine reuptake inhibitors and morphine in the rat formalin model.

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Fei Shen

Full Text Available Multimodal analgesia is designed to optimize pain relief by coadministering drugs with distinct mechanisms of action or by combining multiple pharmacologies within a single molecule. In clinical settings, combinations of monoamine reuptake inhibitors and opioid receptor agonists have been explored and one currently available analgesic, tapentadol, functions as both a µ-opioid receptor agonist and a norepinephrine transporter inhibitor. However, it is unclear whether the combination of selective norepinephrine reuptake inhibition and µ-receptor agonism achieves an optimal antinociceptive synergy. In this study, we assessed the pharmacodynamic interactions between morphine and monoamine reuptake inhibitors that possess different affinities and selectivities for norepinephrine and serotonin transporters. Using the rat formalin model, in conjunction with measurements of ex vivo transporter occupancy, we show that neither the norepinephrine-selective inhibitor, esreboxetine, nor the serotonin-selective reuptake inhibitor, fluoxetine, produce antinociceptive synergy with morphine. Atomoxetine, a monoamine reuptake inhibitor that achieves higher levels of norepinephrine than serotonin transporter occupancy, exhibited robust antinociceptive synergy with morphine. Similarly, a fixed-dose combination of esreboxetine and fluoxetine which achieves comparable levels of transporter occupancy potentiated the antinociceptive response to morphine. By contrast, duloxetine, a monoamine reuptake inhibitor that achieves higher serotonin than norepinephrine transporter occupancy, failed to potentiate the antinociceptive response to morphine. However, when duloxetine was coadministered with the 5-HT3 receptor antagonist, ondansetron, potentiation of the antinociceptive response to morphine was revealed. These results support the notion that inhibition of both serotonin and norepinephrine transporters is required for monoamine reuptake inhibitor and opioid
Mechanisms of the antinociceptive action of (− Epicatechin obtained from the hydroalcoholic fraction of Combretum leprosum Mart & Eic in rodents

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Lopes Luciano da

2012-07-01

Full Text Available Abstract Background The mechanisms of the antinociceptive activity of (− epicatechin (EPI, a compound isolated from the hydroalcoholic fraction of Combreum leprosum Mart & Eicher. Methods were assessed in the model of chemical nociception induced by glutamate (20 μmol/paw. To evaluate the mechanisms involved, the animals , male Swiss mice (25-30 g, received EPI (50 mg/kg p.o. after pretreatment with naloxone (2 mg/kg s.c. opioid antagonist, glibenclamide (2 mg/kg s.c. antagonist K + channels sensitive to ATP, ketanserin (0.3 mg/kg s.c. antagonist of receptor 5-HT2A, yoimbine (0.15 mg/kg s.c. α2 adrenergic receptor antagonist, pindolol (1 mg/kg s.c. 5-HT1a/1b receptor antagonist, atropine (0.1 mg/kg s.c. muscarinic antagonist and caffeine (3 mg/kg s.c. adenosine receptor antagonist, ondansetron (0.5 mg/kg s.c. for 5-HT3 receptor and L-arginine (600 mg/kg i.p.. Results The antinociceptive effect of EPI was reversed by pretreatment with naloxone and glibenclamide, ketanserin, yoimbine, atropine and pindolol, which demonstrates the involvement of opioid receptors and potassium channels sensitive to ATP, the serotoninergic (receptor 5HT1A and 5HT2A, adrenergic (receptor alpha 2 and cholinergic (muscarinic receptor systems in the activities that were observed. The effects of EPI, however, were not reversed by pretreatment with caffeine, L-arginine or ondansetron, which shows that there is no involvement of 5HT3 receptors or the purinergic and nitrergic systems in the antinociceptive effect of EPI. In the Open Field and Rotarod test, EPI had no significant effect, which shows that there was no central nervous system depressant or muscle relaxant effect on the results. Conclusions This study demonstrates that the antinociceptive activity of EPI in the glutamate model involves the participation of the opioid system, serotonin, adrenergic and cholinergic.
Antinociceptive efficacy of buprenorphine and hydromorphone in red-eared slider turtles (Trachemys scripta elegans).

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Mans, Christoph; Lahner, Lesanna L; Baker, Bridget B; Johnson, Stephen M; Sladky, Kurt K

2012-09-01

Despite the frequent clinical use of buprenorphine in reptiles, its antinociceptive efficacy is not known. In a randomized, complete cross-over study, the antinociceptive efficacy of buprenorphine (0.2 mg/kg s.c.) was compared with hydromorphone (0.5 mg/kg s.c.), and saline (0.9% s.c. equivalent volume) in 11 healthy red-eared slider turtles (Trachemys scripta elegans). Additionally, buprenorphine at 0.1 and 1 mg/kg was compared with saline in six turtles. Hindlimb withdrawal latencies were measured after exposure to a focal, thermal noxious stimulus before and between 3 hr and up to 96 hr after drug administration. Buprenorphine did not significantly increase hindlimb withdrawal latencies at any time point compared with saline. In contrast, hydromorphone administration at 0.5 mg/kg significantly increased hindlimb withdrawal latencies for up to 24 hr. These results show that hydromorphone, but not buprenorphine, provides thermal antinociception in red-eared slider turtles.
Bis(phenylimidazoselenazolyl) diselenide elicits antinociceptive effect by modulating myeloperoxidase activity, NOx and NFkB levels in the collagen-induced arthritis mouse model.

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Chagas, Pietro M; Fulco, Bruna C W; Sari, Marcel H M; Roehrs, Juliano A; Nogueira, Cristina W

2017-08-01

Bis(phenylimidazoselenazolyl) diselenide (BPIS) is an organoselenium with acute antinociceptive and antioxidant properties. The aim of this study was to investigate BPIS effect on a collagen-induced arthritis (CIA) model in mice. Protocol of exposure consisted in arthritis induction by chicken collagen type II on day 0 with booster injection on day 21. On day 60 after collagen injection, incidence of mechanic allodynia (Von Frey test) or thermal hyperalgesia (hot plate test) was evaluated. During following 5 days, mice were treated with BPIS (0.1-1 mg/kg; p.o.; daily) or vehicle. On day 65, mice were killed, and paws and spinal cord were removed for analyses. Mice submitted to CIA model developed both mechanical allodynia and thermal hyperalgesia, which were reversed by BPIS at the highest dose. In paw, BPIS reversed the increase in myeloperoxidase activity in the CIA group. In the spinal cord, BPIS decreased NOx and NFkB levels increased in the CIA group. BPIS-treated animals had lower cyclooxygenase-2 levels in the spinal cord. The myeloperoxidase activity in paw and NOx and NFkB levels in spinal cord are related to antinociceptive properties of BPIS in CIA model. © 2017 Royal Pharmaceutical Society.
Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin.

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Jung, Hyun-Joo; Song, Yun Seon; Kim, Kyunghoon; Lim, Chang-Jin; Park, Eun-Hee

2010-02-01

The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn't diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.
Homology-guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2-derived peptides.

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Moutal, Aubin; Li, Wennan; Wang, Yue; Ju, Weina; Luo, Shizhen; Cai, Song; François-Moutal, Liberty; Perez-Miller, Samantha; Hu, Jackie; Dustrude, Erik T; Vanderah, Todd W; Gokhale, Vijay; Khanna, May; Khanna, Rajesh

2017-02-05

N-type voltage-gated calcium (Ca v 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Ca v 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Ca v 2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15-amino-acid peptide (CBD3), derived from CRMP2, disrupts the functional protein-protein interaction between CRMP2 and Ca v 2.2 channels to inhibit calcium influx, transmitter release and acute, inflammatory and neuropathic pain. Here, we have mapped the minimal domain of CBD3 necessary for its antinociceptive potential. Truncated as well as homology-guided mutant versions of CBD3 were generated and assessed using depolarization-evoked calcium influx in rat dorsal root ganglion neurons, binding between CRMP2 and Ca v 2.2 channels, whole-cell voltage clamp electrophysiology and behavioural effects in two models of experimental pain: post-surgical pain and HIV-induced sensory neuropathy induced by the viral glycoprotein 120. The first six amino acids within CBD3 accounted for all in vitro activity and antinociception. Spinal administration of a prototypical peptide (TAT-CBD3-L5M) reversed pain behaviours. Homology-guided mutational analyses of these six amino acids identified at least two residues, Ala1 and Arg4, as being critical for antinociception in two pain models. These results identify an antinociceptive scaffold core in CBD3 that can be used for development of low MW mimetics of CBD3. © 2017 The British Pharmacological Society.
Curcumin attenuates morphine antinociceptive tolerance through suppressing up-regulation of spinal Toll-like receptor 4 in rats

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Fei GAO

2017-12-01

Full Text Available Objective To investigate the effects of curcumin (Cur on activation of spinal Toll-like receptor 4 (TLR4 and on the chronic antinociceptive tolerance of morphine. Methods Sixty male Sprague-Dawley rats with successful intrathecal catheterization were randomly divided into four groups (n=15: saline (NS group; morphine (MOR group; curcumin (Cur group and morphine plus curcumin (MOR+Cur group. A morphine tolerance model of rats was induced by intrathecal injection of morphine 15μg, once a day for 7 consecutive days in MOR and MOR+Cur group; 100μg curcumin was administered intrathecally once a day for 7 consecutive days in Cur and MOR+Cur group, 10μl saline was administered intrathecally once a day for 7 consecutive days in NS group. The effect of curcumin intrathecal catheterization on morphine antinociceptive tolerance was explored by the tail flick latency (TFL method and mechanical withdrawal threshold (MWT, and then the maximum possible potential effect (MPE was calculated. The immunofluorescence staining method was applied to detect the effect of curcumin on the activation of lumbar spinal microglia. Real-time PCR and Western blotting were used to evaluate the effect of curcumin on the expression of mRNA and protein of spinal TLR4. Results The %MPE TFL and %MPE MWT increased significantly in MOR+Cur group than in MOR group (P0.05. The lumbar spinal microglia increased markedly and the expressions of polyclonal antibody IBA-1 and TLR4 were significantly up-regulated in MOR group than in NS group (P0.05. Conclusion Curcumin may attenuate chronic morphine antinociceptive tolerance through inhibiting spinal TLR4 up-regulation. DOI: 10.11855/j.issn.0577-7402.2017.12.06
Substituted galacturonan from starfruit: Chemical structure and antinociceptive and anti-inflammatory effects.

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Leivas, Carolina L; Nascimento, Leandro F; Barros, Wellinghton M; Santos, Adair R S; Iacomini, Marcello; Cordeiro, Lucimara M C

2016-03-01

Starfruit (Averrhoa carambola L.) is an edible tropical fruit, which is usually consumed as a fresh table fruit or as fruit juice. It also exhibits various pharmacological activities. In this study, polysaccharides were extracted with boiling water and purified by freeze-thawing and Fehling treatments. After purification steps, a homogenous fraction was obtained. It was analyzed by sugar composition, gel permeation chromatography, methylation, and two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy analyses. It comprised arabinose (Ara), galactose (Gal), and galacturonic acid (GalA) in a molar ratio of 12.3:1.7:86.0. Methylation and NMR spectroscopy analyses showed that it contained a substituted galacturonan composed of (1→4)-linked α-D-Galp A units branched at O-2 by (1→5)-linked α-L-Araf and terminal α-L-Araf and α-D-Galp A units. The effect of PFSCW (10-300mg/kg, i.p.) on nocifensive behavior induced by intraplantar injection of formalin in mice was evaluated. The fraction demonstrated antinociceptive and anti-inflammatory properties, suggesting that it may be useful in therapeutic intervention for the management of inflammatory pain. Copyright © 2015. Published by Elsevier B.V.
Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

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Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.
Involvement of nitridergic and opioidergic pathways in the antinociception of gabapentin in the orofacial formalin test in mice.

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Miranda, Hugo F; Sierralta, Fernando; Lux, Sebastian; Troncoso, Rocío; Ciudad, Natalia; Zepeda, Ramiro; Zanetta, Pilar; Noriega, Viviana; Prieto, Juan Carlos

2015-04-01

Pain is one of the most common problems in clinical medicine. There is considerable evidence that pharmacologic approaches are the most widely used therapeutic options to ameliorate persistent or chronic pain. In this study it was evaluated the effect of l-NAME and naltrexone in the antinociception induced by administration of gabapentin in the orofacial formalin test of mice. The algesiometer assay was performed by the administration of 20 μl of 2% formalin solution injected into the upper right lip of each mouse. The dose of gabapentin that produces the 50% of the maximum possible effect (ED50) was significantly increased by the pretreatment with l-NAME or naltrexone. These results suggest that gabapentin produce antinociception partly via the activation nitridergic pathways and opioid system. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

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Graziela Vieira

2017-09-01

Full Text Available Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP was induced by ischemia and reperfusion (IR injury of the left hind paw. Our findings showed that simvastatin inhibited mechanical hyperalgesia induced by CPIP model in single and repeated treatment schedules, respectively; however simvastatin did not alter inflammatory signs during CPIP model. The mechanisms underlying those actions are related to modulation of transient receptor potential (TRP channels, especially TRMP8. Moreover, simvastatin oral treatment was able to reduce the nociception induced by acidified saline [an acid-sensing ion channels (ASICs activator] and bradykinin (BK stimulus, but not by TRPA1, TRPV1 or prostaglandin-E2 (PGE2. Relevantly, the antinociceptive effects of simvastatin did not seem to be associated with modulation of the descending pain circuits, especially noradrenergic, serotoninergic and dopaminergic systems. These results indicate that simvastatin consistently inhibits mechanical hyperalgesia during neuropathic and inflammatory disorders, possibly by modulating the ascending pain signaling (TRPM8/ASIC/BK pathways expressed in the primary sensory neuron. Thus, simvastatin open-up new standpoint in the development of innovative analgesic drugs for treatment of persistent pain, including CRPS-I.
Cardiovascular, Antinociceptive and Sedative Effects of Medetomidine Infusion in Sevoflurane Anesthesia in Puppies

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J Morgaz*, JM Domínguez, R Navarrete, JA Fernández-Sarmiento, P Muñoz-Rascón, RJ Gómez-Villamandos and MM Granados

2013-07-01

Full Text Available The objective of this study was to determine the effect of a constant rate infusion of medetomidine in the cortical brain activity and hemodynamic parameters in sevoflurane anesthetized puppies. Six puppies of the age of two weeks old were included in the study and were anaesthetized three times with sevoflurane. On the first anesthesia, each dog’s minimum alveolar concentration (MAC for sevoflurane was determined by the use of the tail clamp method. On the second anesthesia (sevoflurane, the puppies were anesthetized at each of five multiples of their individual’s MAC, 0.75, 1, 1.25, 1.5 and 1.75 MAC, and bispectral index and cardiorespiratory parameters were registered. On the third anesthesia (sevoflurane+ medetomidine, puppies were anesthetized at each of five multiples of their individual’s MAC, and medetomidine (5 µg/kg+2µg/kg/h was administered. Mild cardiovascular depression was observed in sevoflurane+medetomidine in comparison with sevoflurane. Cortical and antinociceptive effects were not observed with medetomidine infusion although a mature EEG response to noxious stimulation would not have developed in puppies. Central alpha-2 adrenoreceptors would be immature in puppies during the first two weeks of life, and for this reason, medetomidine would not produce sedative and analgesic effects in young puppies. More studies have to be performed to support this statement.
Chemical composition, antinociceptive and anti-inflammatory effects in rodents of the essential oil of Peperomia serpens (Sw.) Loud.

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Pinheiro, B G; Silva, A S B; Souza, G E P; Figueiredo, J G; Cunha, F Q; Lahlou, S; da Silva, J K R; Maia, J G S; Sousa, P J C

2011-11-18

Peperomia serpens (Piperaceae), popularly known as "carrapatinho", is an epiphyte herbaceous liana grown wild on different host trees in the Amazon rainforest. Its leaves are largely used in Brazilian folk medicine to treat inflammation, pain and asthma. This study investigated the effects of essential oil of Peperomia serpens (EOPs) in standard rodent models of pain and inflammation. The antinociceptive activity was evaluated using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception in mice whereas the anti-inflammatory activity was evaluated by carrageenan- and dextran-induced paw edema tests in rats croton oil-induced ear edema, as well as cell migration, rolling and adhesion induced by carrageenan in mice. Additionally, phytochemical analysis of the EOPs has been also performed. Chemical composition of the EOPs was analyzed by gas chromatography and mass spectrometry (GC/MS). Twenty-four compounds, representing 89.6% of total oil, were identified. (E)-Nerolidol (38.0%), ledol (27.1%), α-humulene (11.5%), (E)-caryophyllene (4.0%) and α-eudesmol (2.7%) were found to be the major constituents of the oil. Oral pretreatment with EOPs (62.5-500 mg/kg) significantly reduced the writhing number evoked by acetic acid injection, with an ED(50) value of 188.8 mg/kg that was used thereafter in all tests. EOPs had no significant effect on hot plate test but reduced the licking time in both phases of the formalin test, an effect that was not significantly altered by naloxone (0.4 mg/kg, s.c.). EOPs inhibited the edema formation induced by carrageenan and dextran in rats. In mice, EOPs inhibited the edema formation by croton oil as well as the leukocyte and neutrophil migration, the rolling and the adhesion of leukocytes. These data show for the first time that EOPs has a significant and peripheral antinociceptive effect that seems unrelated to interaction with the opioid system. EOPs also displays a significant anti-inflammatory effect in
A report of a galactan from marine alga Gelidium crinale with in vivo anti-inflammatory and antinociceptive effects.

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de Sousa, Albertina A S; Benevides, Norma M B; de Freitas Pires, Alana; Fiúza, Felipe P; Queiroz, Maria G R; Morais, Thamires M F; Pereira, Maria G; Assreuy, Ana M S

2013-04-01

The sulfated galactan of the red marine alga Gelidium crinale (SG-Gc) was purified by ion exchange chromatography and tested by intravenous (i.v.) route in rodent experimental models of inflammation and nociception. The anti-inflammatory activity of SG-Gc (0.01, 0.1 and 1 mg/kg) was evaluated in the model of rat paw edema induced by different inflammatory stimuli, while SG-Gc (0.1, 1 and 10 mg/kg) antinociceptive effect was assessed in models of nociception/hyperalgesia elicited by chemical (formalin test), thermal (hot plate), and mechanical (von Frey) stimuli in mice. In addition, the toxicity was evaluated after rat treatment with SG-Gc (1 mg/kg; i.v.) during 10 days, followed by analysis of the wet weight of animal's body/organs and hematological/biochemical parameters. Sulfated galactan of G. crinale inhibited the time course of dextran-induced paw edema, at all doses, showing maximal effect at 1 mg/kg (42%) and that induced by carrageenan at 0.01 (18%) and 1 mg/kg (20%), but was ineffective on the edema elicited by zymosan. At the highest dose, SG-Gc also inhibited the paw edema induced by histamine (49%), compound 48/80 (32%), and phospholipase A(2) (44%). Sulfated galactan of G. crinale inhibited both neurogenic and inflammatory phases of the formalin test, at all doses, and at 10 mg/kg, the animals flinch reaction in the von Frey test in the 1st and 3rd h by 19 and 26%, respectively. Additionally, SG-Gc treatment was well tolerated by animals. In conclusion, SG-Gc presents anti-inflammatory effect involving the inhibition of histamine and arachidonic acid metabolites and also antinociceptive activity, especially the inflammatory pain with participation of the opioid system. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.
Effects of oxymorphazone in frogs: long lasting antinociception in vivo, and apparently irreversible binding in vitro

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Benyhe, S.; Hoffman, G.; Varga, E.; Hosztafi, S.; Toth, G.; Borsodi, A.; Wollemann, M.

1989-01-01

Oxymorphazone was found to be a relatively weak antinociceptive drug in intact frog (Rana esculenta) when acetic acid was used as pain stimulus. Frogs remained analgesic for at least 48 hrs following oxymorphazone administration. The ligand increased the latency of wiping reflex in spinal frogs too. There effects were blocked by naloxone. In equilibrium binding studies (/sup 3/H)oxymorphazone had high affinity to the opioid receptors of frog brain and spinal cord as well. Kinetic experiments show that only 25% of the bound (/sup 3/H)oxymorphazone is readily dissociable. Preincubation of the membranes with labeled oxymorphazone results in a washing resistant inhibition of the opioid binding sites. At least 70% of the (/sup 3/H)oxymorphazone specific binding is apparently irreversible after reaction at 5 nM ligand concentration, and this can be enhanced by a higher concentration of tritiated ligand.
Antinociceptive potential of viscosine isolated form dodonaea viscose in animal models

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Khan, A.Z.

2014-01-01

Dodonaea viscosa was selected in this study based on its ethno-medicinal applications for treating various painful conditions. In earlier studies crude extracts of Dodonaea viscosa showed significant actions as local anesthetic, smooth muscle relaxant, antibacterial, anti-inflammatory, antifungal, anti-ulcerogenic, anti-ascariasis, anthelmintic, cardiac depressant, hypotensive, uterine relaxation and vasoconstrictor activity in different experimental models. In an effort to identify the potential analgesic components of the plant, the principal flavonoid constituent, 5,7,4-trihydroxy-3,6-dimethoxyflavone (viscosine) was isolated. When tested using the acetic acid-induced writhing and hot plate analgesic models, viscosine (30, 45 and 60 mg/kg), showed significant (p < 0.05) antinociceptive activity in a dose-dependent manner. It is concluded that viscosine has antinociceptive therapeutic potential through both central and peripheral mechanisms and can be used a template compound as a painkiller. (author)
Antinociceptive and hypothermic evaluation of the leaf essential oil and isolated terpenoids from Eugenia uniflora L. (Brazilian Pitanga).

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Amorim, Ana Carolina L; Lima, Cleverton Kleiton F; Hovell, Ana Maria C; Miranda, Ana Luisa P; Rezende, Claudia M

2009-10-01

Eugenia uniflora L. (Myrtaceae), known as Brazilian cherry tree, is a fruity tree spread all over Brazil used in popular medicine to treat inflammations, rheumatic pain and fever, as hypoglycemic, diuretic and has been widely used in the cosmetics industry. The present study discusses the chemical composition, the antinociceptive and hypothermic profile of the essential oil of pitangueira leaves. The chemical composition was evaluated by GC-MS and the main constituent of the oil was characterized, after isolation, as a mixture of atractylone (1) and 3-furanoeudesmene (2). The essential oil, its pentane fraction and the isolated mixture of sesquiterpenes (1 and 2), given orally, significantly inhibited the acetic acid-induced abdominal constrictions, increased the latency time in hot plate test and showed a hypothermic effect. The results suggest that the responsible for the antinociceptive and hypothermic effect were the isolated furanosesquiterpenes. These findings provided additional pharmacological information and may contribute for the use of Brazilian cherry tree as a phytomedicine.
Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus (Myrtaceae

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Joelma Abadia Marciano de Paula

2012-01-01

Full Text Available Preparations from Pimenta pseudocaryophyllus (Gomes L.R. Landrum (Myrtaceae have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR. The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1, followed by the essential oil of the citral chemotype (62.5–250 μg mL−1. Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1 and Cryptococcus spp. (3.9–15.6 μg mL−1. The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects.
Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

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Li He

Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.

Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

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Vats, Ishwar Dutt; Chaudhary, Snehlata; Sharma, Ahuti; Nath, Mahendra; Pasha, Santosh

2010-07-25

The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e., Y-(D-Ala)-G-(p-Cl-Phe)-MKKKFMRFamide ([D-Ala(2), p-Cl-Phe(4)]YFa) in order to achieve improved bioavailability and blood brain barrier penetration. Therefore, present study investigates the possible antinociceptive effect of [D-Ala(2), p-Cl-Phe(4)]YFa on intra-peritoneal (i.p.) administration using tail-flick test in rats followed by its opioid receptor(s) specificity using mu, delta and kappa receptor antagonists. Further, its antinociceptive effect was examined during 6 days of chronic i.p. treatment and assessed effect of this treatment on differential expression of opioid receptors. [D-Ala(2), p-Cl-Phe(4)]YFa in comparison to parent peptide YFa, induce significantly higher dose dependent antinociception in rats which was mediated by all three opioid receptors (mu, delta and kappa). Importantly, it induced comparable antinociception in rats throughout the chronic i.p. treatment and significantly up-regulated the overall expression (mRNA and protein) of mu, delta and kappa opioid receptors. Therefore, pharmacological and molecular behavior of [D-Ala(2), p-Cl-Phe(4)]YFa demonstrate that incorporation of D-alanine and p-Cl-phenylalanine residues at appropriate positions in chimeric peptide leads to altered opioid receptor selectivity and enhanced antinociceptive potency, relative to parent peptide. (c) 2010 Elsevier B.V. All rights reserved.
Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.

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Aman, Urooj; Subhan, Fazal; Shahid, Muhammad; Akbar, Shehla; Ahmad, Nisar; Ali, Gowhar; Fawad, Khwaja; Sewell, Robert D E

2016-02-24

Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI
Antinociceptive and Anti-Inflammatory Activities of Teucrium persicum Boiss. Extract in Mice

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Abdolhossein Miri

2015-01-01

Full Text Available Background. Therapeutic properties of Teucrium species as antioxidant, antibacterial, analgesic, anticancer, diuretic, and tonic compounds have been proved earlier. Materials and Methods. In this study, the antinociceptive and anti-inflammatory effects of the aqueous extract of Teucrium persicum on chronic pain, sciatic nerve ligation as a model of neuropathic pain, and inflammatory models were investigated by formalin, hot-plate, and cotton pellet-induced granuloma models in mice, respectively. T. persicum aqueous extracts (100, 200, and 400 mg/kg were orally gavaged for one week. On 8th day, the time spent and the number of lickings were recorded in formalin test. Morphine and Diclofenac were used intraperitoneally as positive controls. In sciatic nerve ligated animals, as a model of neuropathic pain, doses (100, 200, and 400 mg/kg of T. persicum extract (TPE were orally gavaged for 14 consecutive days. The analgesic effect of this extract was examined 14 days after sciatic nerve ligation using the hot-plate test. Controls received saline and Imipramine (40 mg/kg, i.p. was used a positive control for neuropathic pain model. Results. In the formalin test, a week oral gavage of all TPE doses (100, 200, and 400 mg/kg caused a significant decrease on the licking response compared to the control negative animals. In the hot-plate test, doses of 200 and 400 mg/kg showed significant analgesic effects in sciatic nerve ligated animals. Oral gavaged of TPE revealed significant analgesic effect on chronic pain in both formalin test and sciatic nerve ligated animals. The TPEs did not have any significant anti-inflammatory effects in cotton pellet-induced granuloma formation in mice. Conclusions. These results suggest that the aqueous extract from T. persicum Boiss. produced antinociceptive effects. Its exact mechanism of action still remains indistinct.
St36 electroacupuncture activates nNOS, iNOS and ATP-sensitive potassium channels to promote orofacial antinociception in rats.

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Almeida, R T; Galdino, G; Perez, A C; Silva, G; Romero, T R; Duarte, I D

2017-02-01

Orofacial pain is pain perceived in the face and/or oral cavity, generally caused by diseases or disorders of regional structures, by dysfunction of the nervous system, or through referral from distant sources. Treatment of orofacial pain is mainly pharmacological, but it has increased the number of reports demonstrating great clinical results with the use of non-pharmacological therapies, among them electroacupuncture. However, the mechanisms involved in the electroacupuncture are not well elucidated. Thus, the present study investigate the involvement of the nitric oxide synthase (NOS) and ATP sensitive K + channels (KATP) in the antinociception induced by electroacupuncture (EA) at acupoint St36. Thermal nociception was applied in the vibrissae region of rats, and latency time for face withdrawal was measured. Electrical stimulation of acupoint St36 for 20 minutes reversed the thermal withdrawal latency and this effect was maintained for 150 min. Intraperitoneal administration of specific inhibitors of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and a KATP channels blocker reversed the antinociception induced by EA. Furthermore, nitrite concentration in cerebrospinal fluid (CSF) and plasma, increased 4 and 3-fold higher, respectively, after EA. This study suggests that NO participates of antinociception induced by EA by nNOS, iNOS and ATP-sensitive K + channels activation.
Study of antinociceptive activity of SSRI (fluoxetine and escitalopram and atypical antidepressants (venlafaxine and mirtazepine and their interaction with morphine and naloxone in mice

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Pranav Sikka

2011-01-01

Full Text Available Objective : to study the probable site of antinociceptive action of SSRI (fluoxetine, escitalopram and atypical antidepressants (mirtazapine, venlafaxine and their interaction with morphine and naloxone. Materials and Methods : the study was conducted on albino mice (25-35 grams of either sex. Different doses of morphine (0.5 and 1 mg/kg, fluoxetine (2, 5 and 10 mg/kg, venlafaxine (30, 40 and 50 mg/kg, mirtazapine (3, 5 and 7 mg/kg and escitalopram (2.5, 5 and 10 mg/kg were administered subcutaneously to obtain their subanalgesic doses using tail flick analgesiometer. Tail flick latencies were obtained at 15, 30, 60 and 120 min. after drug administration. Naloxone (1 mg/kg was administered 10 minutes prior to test drug for testing antagonism. Observations : fluoxetine (5 and 10 mg/kg, mirtazapine (5 and 7 mg/kg and venlafaxine (40 and 50 mg/kg were found to have antinociceptive activity but not at lower doses. Escitalopram failed to show any antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone (1 mg/kg. Further, subanalgesic doses of fluoxetine, mirtazapine and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg. Result and conclusion : fluoxetine, mirtazapine and venlafaxine have antinociceptive activity whereas escitalopram doesn′t; their site of action seems to be the same as that of opioid analgesics (′mue′ receptors. However, other pathways (cholinergic, histaminic, noradrenergic, GABAergic may be involved in mediation of their analgesic activity, deserving further elucidation. Results apparently show that these drugs may be useful in the management of pain as monotherapy or in combination with other opioids.
Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

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István Z. Bátai

2018-02-01

Full Text Available Transient receptor potential ankyrin 1 (TRPA1 non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS. In the frame of the present study, we set out to compare the participation of this mechanism in antinociceptive and anti-inflammatory effects of inorganic sodium POLY and DMTS in carrageenan-evoked hind-paw inflammation. Inflammation of murine hind paws was induced by intraplantar injection of carrageenan (3% in 30 µL saline. Animals were treated intraperitoneally with POLY (17 µmol/kg or DMTS (250 µmol/kg or their respective vehicles 30 min prior paw challenge and six times afterward every 60 min. Mechanical pain threshold and swelling of the paws were measured by dynamic plantar aesthesiometry and plethysmometry at 2, 4, and 6 h after initiation of inflammation. Myeloperoxidase (MPO activity in the hind paws were detected 6 h after challenge by luminescent imaging. Mice genetically lacking TRPA1 ion channels, sst4 receptors and their wild-type counterparts were used to examine the participation of these proteins in POLY and DMTS effects. POLY counteracted carrageenan-evoked mechanical hyperalgesia in a TRPA1 and sst4 receptor-dependent manner. POLY did not influence paw swelling and MPO activity. DMTS ameliorated all examined inflammatory parameters. Mitigation of mechanical hyperalgesia and paw swelling by DMTS were mediated through sst4 receptors. These effects were present in TRPA1 knockout animals, too. DMTS inhibited MPO activity with no participation of the sensory neuron–SOM axis. While antinociceptive effects of
Antinociceptive effects of an extract, fraction and an isolated compound of the stem bark of Maytenus rigida

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Marina V. Martins

2012-01-01

Full Text Available The antinociceptive activity of the Maytenus rigida Mart. (Celastraceae ethanol extract and its ethyl acetate fraction as well as of (--4'-methylepigallocatechin (1, a previously isolated compound, was demonstrated in vivo. ED50 for 1 in the writhing test was 14.14 mg/kg. The acetic acid-induced writhing was inhibited by 98.4, 84.4, and 58.3%, respectively, when mice were treated with the ethanol extract, ethyl acetate fraction, and 1. In the hot plate test, mice pretreated with 1 showed significantly increased reaction times (60-89%. Oral administration of 1 significantly inhibited first and second phases of the formalin-induced pain (50 and 26.5%, respectively, whereas indomethacin inhibited only the second phase of the test (41.2%. Ethanol extract and its fraction showed effects on inflammatory pain, while neurogenic and inflammatory pain suppression by 1 is a strong indication of the presence of both central and peripheral effects and suggests its analgesic and anti-inflammatory potential.
Antinociceptive effects of an extract, fraction and an isolated compound of the stem bark of Maytenus rigida

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Marina V. Martins

2012-06-01

Full Text Available The antinociceptive activity of the Maytenus rigida Mart. (Celastraceae ethanol extract and its ethyl acetate fraction as well as of (--4'-methylepigallocatechin (1, a previously isolated compound, was demonstrated in vivo. ED50 for 1 in the writhing test was 14.14 mg/kg. The acetic acid-induced writhing was inhibited by 98.4, 84.4, and 58.3%, respectively, when mice were treated with the ethanol extract, ethyl acetate fraction, and 1. In the hot plate test, mice pretreated with 1 showed significantly increased reaction times (60-89%. Oral administration of 1 significantly inhibited first and second phases of the formalin-induced pain (50 and 26.5%, respectively, whereas indomethacin inhibited only the second phase of the test (41.2%. Ethanol extract and its fraction showed effects on inflammatory pain, while neurogenic and inflammatory pain suppression by 1 is a strong indication of the presence of both central and peripheral effects and suggests its analgesic and anti-inflammatory potential.
Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance.

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Wang, Zi-Long; Li, Ning; Wang, Pei; Tang, Hong-Hai; Han, Zheng-Lan; Song, Jing-Jing; Li, Xu-Hui; Yu, Hong-Ping; Zhang, Ting; Zhang, Run; Xu, Biao; Zhang, Meng-Na; Fang, Quan; Wang, Rui

2016-09-01

Mounting evidences indicate the functional interactions between neuropeptide FF (NPFF) and opioids, including the endogenous opioids. In the present work, EN-9, a chimeric peptide containing the functional domains of the endogenous opioid endomorphin-2 (EM-2) and NPFF, was synthesized and pharmacologically characterized. In vitro cAMP assay demonstrated that EN-9 was a multifunctional agonist of κ-opioid, NPFF1 and NPFF2 receptors. In the mouse tail-flick test, intracerebroventricularly (i.c.v.) administration of EN-9 produced significant antinociception with an ED50 value of 13.44 nmol, which lasted longer than that of EM-2. In addition, EN-9 induced potent antinociception after both intravenous (i.v.) and subcutaneous (s.c.) injection. Furthermore, the experiments using the antagonists of opioid and NPFF receptors indicated that the central antinociception of EN-9 was mainly mediated by κ-opioid receptor, independently on NPFF receptors. Notably, the central antinociception of EN-9 was not reduced over a period of 6 days repeated i.c.v. injection. Repeated i.c.v. administration of EN-9 with the NPFF1 and NPFF2 receptors antagonist RF9 resulted in a progressive loss of analgesic potency, consistent with the development of tolerance. Moreover, central administration of EN-9 induced the place conditioning aversion only at a high dose of 60 nmol, but not at low doses. At supraspinal level, only high dose of EN-9 (60 nmol, i.c.v.) inhibited gastrointestinal transit via NPFF receptors. Similarly, systemic administration of EN-9 also inhibited gastrointestinal transit at high doses (10 and 30 mg/kg, i.v.). Taken together, the multifunctional agonist of κ-opioid and NPFF receptors EN-9 produced a potent, non-tolerance forming antinociception with limited side effects. Copyright © 2016. Published by Elsevier Ltd.
Antinociceptive and Anti-Inflammatory Activities of the Ethanolic Extract from Synadenium umbellatum Pax. (Euphorbiaceae Leaves and Its Fractions

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Rodrigo Borges

2013-01-01

Full Text Available Synadenium umbellatum Pax., popularly known in Brazil as “cola-nota,” “avelós,” “cancerola,” and “milagrosa”, is a plant species used in folk medicine for the treatment of inflammation, pain, and several diseases. This study aimed to investigate the antinociceptive and anti-inflammatory activities of the ethanolic extract from Synadenium umbellatum Pax. leaves (EES and its hexane (HF, chloroform (CF, and methanol/water (MF fractions using the acetic acid-induced abdominal writhing test, formalin-induced paw licking test, tail flick test, croton oil-induced ear edema test, and carrageenan-induced peritonitis test. EES and MF reduced the number of acetic acid-induced abdominal writhes, while CF and HF did not. EES effect on acetic acid-induced abdominal writhing was reversed with a pretreatment with naloxone. EES reduced licking time in both phases of the formalin-induced paw licking test, but did not prolong the latency in the tail flick test. These results show that EES presented antinociceptive activity, probably involving the opioid system, anti-inflammatory activity in the croton oil-induced ear edema test, and leukocyte migration into the intraperitoneal cavity. MF also presented anti-inflammatory activity in the croton oil-induced ear edema test. In conclusion, EES and MF have antinociceptive activity involving the opioid system and anti-inflammatory activity.
[Suppression of visceral pain by action of the low intensity polarized light on acupuncture antinociceptive points].

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Lymans'kyĭ, Iu P; Tamarova, Z A; Huliar, S O

2003-01-01

In experiments on mice, statistically authentic weakening of visceral pain has been shown after an action of low intensity polarized light from a device Bioptron on antinociceptive acupuncture points (AP). Pain was caused by an intraperitoneal injection of 2% acetic acid (0.1 ml/10 g). The intensity of pain was judged on duration and frequency of painful behavioral reactions (writhing, licking of abdomen), as well as on duration of sleep, eating and motor activity. In animals which immediately after injections of acetic acid were exposed to polarized light of low intensity for 10 min, applied on any of antinociceptive APs (E-36, E-43, VC-8, RP-6), the duration of painful behavioral reaction was determined to be reduced, while that of non-painful one increased. The comparison of the total duration of the writhing at control and experimental mice showed that an activation of AP E-43 induced the greatest analgesic effect (76.5%), from AP VC-8 it was 76.3%, from RP-6--46.8%, and from E-36--41.4%. We have concluded that the effect of polarized light of low intensity on APs was a convenient non-pharmacological method of treating visceral pain.
Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

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Danielle Ingrid Bezerra de Vasconcelos

2011-01-01

Full Text Available Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.
Antinociceptive synergism of gabapentin and nortriptyline in mice with partial sciatic nerve ligation.

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Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro; Zanetta, Pilar; Prieto-Rayo, Josefina; Prieto, Juan Carlos; Sierralta, Fernando

2015-01-01

Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis. Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED50 of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1 ratio of their ED50, had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively. The data showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alternative that can be used for neuropathic pain management. © 2015 S. Karger AG, Basel.
Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin.

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Mansouri, Mohammad Taghi; Khodayar, Mohammad Javad; Tabatabaee, Amirhossein; Ghorbanzadeh, Behnam; Naghizadeh, Bahareh

2015-10-01

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previous studies have demonstrated the neuroprotective effects of simvastatin in different animal models. In the present study, we examined the effects of simvastatin (30, 60, 100 and 300mg/kg, p.o.) on the development and expression of morphine-induced tolerance and dependence in mice. For the induction of morphine tolerance and dependence, mice were twice daily treated with morphine (10mg/kg, s.c.) for 5 consecutive days. Tolerance was evaluated by the hot-plate test and physical dependence by naloxone challenge, on the sixth day. The results showed that oral administration of simvastatin produced antinociceptive activity in a dose-dependent way. Co-administration of simvastatin with morphine did not affect the acute morphine-induced analgesia (10mg/kg, s.c.). However, repeated co-administration of simvastatin with morphine significantly attenuated the development of tolerance to the analgesic effect of morphine and inhibited the naloxone (5mg/kg, s.c.)-precipitated withdrawal signs (jumping and body weight loss). Also, simvastatin at doses of 100 and 300mg/kg attenuated the expression of morphine-induced tolerance and dependence. These data indicated that, while simvastatin can alleviate both development and expression of morphine-induced tolerance, it cannot enhance morphine-induced antinociception. Taken together, simvastatin may be used as an adjutant therapeutic agent in combination with morphine and or other opioids in patients with severe chronic pain. Copyright © 2015 Elsevier Inc. All rights reserved.
Chemical composition and evaluation of antinociceptive activity of the essential oil of Stevia serrata Cav. from Guatemala.

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Reis Simas, Daniel Luiz; Mérida-Reyes, Max Samuel; Muñoz-Wug, Manuel Alejandro; Cordeiro, Millena Santos; Giorno, Thais Biondino Sardella; Taracena, Edwin Adolfo; Oliva-Hernández, Bessie Evelyn; Martínez-Arévalo, José Vicente; Fernandes, Patricia Dias; Pérez-Sabino, Juan Francisco; Jorge Ribeiro da Silva, Antonio

2017-11-13

The composition and the antinociceptive activity of the essential oil of Stevia serrata Cav. from a population located in the west highlands of Guatemala were evaluated. A yield of 0.2% (w/w) of essential oil was obtained by hydrodistillation of the dried aerial parts of the plant. The essential oil analysed by GC-FID and GC-MS showed a high content of sesquiterpenoids, with chamazulene (60.1%) as the major component and 91.5% of the essential oil composition was identified. To evaluate antinociceptive activity in mice, the essential oil of S. serrata Cav. was administered as gavage, using three different doses. In the formalin test, the animals were pre-treated with oral doses of the essential oil before the administration of formalin. Oral administration of S. serrata Cav. essential oil produced a marked antinociceptive activity. Therefore, the plant could be domesticated as a source of essential oil rich in chamazulene for developing medicinal products.
Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

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Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation
Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).

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Jørgensen, Kristine B; Krogh-Jensen, Karen; Pickering, Darryl S; Kanui, Titus I; Abelson, Klas S P

2016-01-01

The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.
Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats

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Toshikatsu Okumura

2016-02-01

Subcutaneously (80 mg/rat or intracisternally (2.5 μg/rat administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.
Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

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Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

2011-07-01

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.
Antiinflammatory, antinociceptive and antipyretic effects of hydroethanolic extract from Macrosiphonia velame (A. St.-Hil. M. Arg. in animal models

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Reginaldo Vicente Ribeiro

2010-09-01

Full Text Available Macrosiphonia velame (Apocynaceae, popularly known as "velame-branco", is mainly used for treating inflammatory conditions. The antiinflammatory, antinociceptive and antipyretic effects of the hydroethanolic extract of the xylopodium from M. velame (HEMv were evaluated using several animal models. HEMv showed low acute oral toxicity with LD50 of 4.176 ± 218.5 mg/kg in mice. In tests of carrageenan and dextran-induced paw edema and carrageenan-induced pleurisy in rats, and croton oil-induced cutaneous dermatitis in mice, HEMv presented systemic and topical antiinflammatory activities. In experiments of nociception induced by acetic acid, formalin and capsaicin in mice, the HEMv evidenced an antinociceptive effect, being active against both inflammatory and neurogenic pain. Additionally, the HEMv prevented brewer's yeast-induced pyrexia in rats. It is likely that the pharmacologic mechanism of HEMv may involve the inhibition of different mediators of the inflammatory response, such as histamine, serotonin, prostaglandins and leukotrienes. A preliminary phytochemical study was also undertaken on HEMv, which revealed the presence of flavonoids, phenolic compounds, pentacyclic triterpenoids, saponins, coumarins, catechins, tannins, and alkaloids. Taken together, these results suggest that M. velame extract has antiinflammatory, antinociceptive and antipyretic properties and further validate the traditional use of this plant in inflammatory conditions.Macrosiphonia velame (Apocynaceae, conhecida popularmente como velame-branco, é utilizada no tratamento de inflamações. Avaliou-se nesse estudo, os efeitos antiinflamatório, antinociceptivo e antipirético do extrato hidroetanólico do xilopódio de M. velame (HEMv em modelos animais. O HEMv apresentou baixa toxicidade aguda oral, com DL50= 4.176 ± 218,5 mg/kg nos camundongos. Nos testes de edema de pata por carragenina e dextrana e pleurisia por carragenina em ratos e dermatite cutânea por �

Antinociceptive Grayanoids from the Roots of Rhododendron molle.

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Li, Yong; Liu, Yun-Bao; Zhang, Jian-Jun; Liu, Yang; Ma, Shuang-Gang; Qu, Jing; Lv, Hai-Ning; Yu, Shi-Shan

2015-12-24

Nine new grayanoids (1-9), together with 11 known compounds, were isolated from the roots of Rhododendron molle. The structures of the new compounds (1-9) were determined on the basis of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR data. Compounds 4, 6, 12, and 14-20 showed significant antinociceptive activities in an acetic acid-induced writhing test. In particular, 14 and 15 were found to be more potent than morphine for both acute and inflammatory pain models and 100-fold more potent than gabapentin in a diabetic neuropathic pain model.
Multivariate analysis in the evaluation of the antinociceptive activity of irradiated essential oil of nutmeg

International Nuclear Information System (INIS)

Santos, Marcelo C.; Lima, Keila S.C.; Oliveira, Sergio E.M.; Lima, Antonio L.S.; Silva, Jose C.C.; Silva, Otniel F.

2013-01-01

Used in spices and for medicinal purposes, nutmeg is the seed of the nutmeg tree, Myristica Fragans Houttyn. This species is reported to contain 25-30% fixed oils, 5-15% volatile oils and several chemical substances. Among these substances, there are isosafrole, the elemicida and myristicin, known to be hallucinogenic and toxic, when in large quantities. Irradiation is a technique that consists in submitting products to ionizing radiation, in order to get technological improvements. In this context, the process of gamma radiation was used to investigate its effects on the antinociceptive activity of the nutmeg essential oil. Employing low doses of radiation, the objective was to verify possible changes in this activity, by performing in vivo tests. In this work the essential oil was analyzed by GC-GC/MS using the MDGC technique. The essential oil extraction was carried out by steam distillation, using the modified Clevenger apparatus. The samples were irradiated in a research irradiator with cesium-137 source, at doses of 1.0, 3.0 and 5.0 kGy, with dose rate 1.8 kGy / h. The Shimadzu MDGC system consisted of two GC-2010 gas chromatographs (defined as GC 1 and GC 2), an MS-QP2010 quadrupole mass spectrometer. The MDGC transfer device, located in GC 1, is connected to an advanced pressure control (APC) unit which supplies carrier gas (He), at constant pressure. In the first GC it was used an HP-FFAP 25m x 0,20 mm i.d. x 0,33μm (Agilent) and in the second GC a Rtx-5MS 30m x 0,25mm i.d. x 0,25μm (Restek) as columns. Mass Ion source: 250 deg C; interface temp: 250 deg C, interval scan: 40-400 m/z; scan speed: 2000 amu/s. The in vivo tests were performed using injection of an acetic acid solution 0,6%. Five minutes after the stimulus the counting was initiated, continuing for the subsequent 10 minutes. Thirty-five substances were identified in the extracted essential oil. After induction of pain in mice by injection of acetic acid, the antinociceptive effects of a
Multivariate analysis in the evaluation of the antinociceptive activity of irradiated essential oil of nutmeg

Energy Technology Data Exchange (ETDEWEB)

Santos, Marcelo C.; Lima, Keila S.C.; Oliveira, Sergio E.M.; Lima, Antonio L.S., E-mail: marcelocdossantos@yahoo.com.br [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil); Silva, Jose C.C., E-mail: pinto@peq.coppe.ufrj.br [Coordenacao do Programas de Pos-Graduacao em Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil); Silva, Otniel F., E-mail: otniel.freitas@embrapa.br [Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA), Rio de Janeiro, RJ (Brazil)

2013-07-01

Used in spices and for medicinal purposes, nutmeg is the seed of the nutmeg tree, Myristica Fragans Houttyn. This species is reported to contain 25-30% fixed oils, 5-15% volatile oils and several chemical substances. Among these substances, there are isosafrole, the elemicida and myristicin, known to be hallucinogenic and toxic, when in large quantities. Irradiation is a technique that consists in submitting products to ionizing radiation, in order to get technological improvements. In this context, the process of gamma radiation was used to investigate its effects on the antinociceptive activity of the nutmeg essential oil. Employing low doses of radiation, the objective was to verify possible changes in this activity, by performing in vivo tests. In this work the essential oil was analyzed by GC-GC/MS using the MDGC technique. The essential oil extraction was carried out by steam distillation, using the modified Clevenger apparatus. The samples were irradiated in a research irradiator with cesium-137 source, at doses of 1.0, 3.0 and 5.0 kGy, with dose rate 1.8 kGy / h. The Shimadzu MDGC system consisted of two GC-2010 gas chromatographs (defined as GC 1 and GC 2), an MS-QP2010 quadrupole mass spectrometer. The MDGC transfer device, located in GC 1, is connected to an advanced pressure control (APC) unit which supplies carrier gas (He), at constant pressure. In the first GC it was used an HP-FFAP 25m x 0,20 mm i.d. x 0,33μm (Agilent) and in the second GC a Rtx-5MS 30m x 0,25mm i.d. x 0,25μm (Restek) as columns. Mass Ion source: 250 deg C; interface temp: 250 deg C, interval scan: 40-400 m/z; scan speed: 2000 amu/s. The in vivo tests were performed using injection of an acetic acid solution 0,6%. Five minutes after the stimulus the counting was initiated, continuing for the subsequent 10 minutes. Thirty-five substances were identified in the extracted essential oil. After induction of pain in mice by injection of acetic acid, the antinociceptive effects of a
Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

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Wijethilake, Chaminda

2017-07-01

This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.
Peripheral and spinal 5-HT receptors participate in the pronociceptive and antinociceptive effects of fluoxetine in rats.

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Cervantes-Durán, C; Rocha-González, H I; Granados-Soto, V

2013-11-12

The role of 5-HT receptors in fluoxetine-induced nociception and antinociception in rats was assessed. Formalin produced a typical pattern of flinching and licking/lifting behaviors. Local peripheral ipsilateral, but not contralateral, pre-treatment with fluoxetine (0.3-3 nmol/paw) increased in a dose-dependent fashion 0.5% formalin-induced nociception. In contrast, intrathecal pretreatment with fluoxetine (0.3-3 nmol/rat) prevented nociception induced by formalin. The peripheral pronociceptive effect of fluoxetine was prevented by the 5-HT2A (ketanserin, 3-10 pmol/paw), 5-HT2B (3-(2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl)-2,4(1H,3H)-quinazolinedione(+) tartrate, RS-127445, 3-10 pmol/paw), 5-HT2C (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido) phenyl-5-oxopentyl]1,3,8-triazaspiro[4.5] decane-2,4-dione hydrochloride, RS-102221, 3-10 pmol/paw), 5-HT3 (ondansetron, 3-10 nmol/paw), 5-HT4 ([1-[2-methylsulphonylamino ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate, GR-113808, 3-100 fmol/paw), 5-HT6 (4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride, SB-258585, 3-10 pmol/paw) and 5-HT7 ((R)-3-(2-(2-(4-methylpiperidin-1-yl) ethyl) pyrrolidine-1-sulfonyl) phenol hydrochloride, SB-269970, 0.3-1 nmol/paw), but not by the 5-HT1A (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate, WAY-100635, 0.3-1 nmol/paw), 5-HT1B/1D (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide hydrochloride hydrate, GR-127935, 0.3-1 nmol/paw), 5-HT1B (1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine hydrochloride, SB-224289, 0.3-1 nmol/paw), 5-HT1D (4-(3-chlorophenyl)-α-(diphenylmethyl)-1-piperazineethanol hydrochloride, BRL-15572, 0.3-1nmol/paw) nor 5-HT5A ((N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4
Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

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Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006
Tecoma sambucifolia: anti-inflammatory and antinociceptive activities, and 'in vitro' toxicity of extracts of the 'huarumo' of peruvian incas.

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Alguacil, L F; Galán de Mera, A; Gómez, J; Llinares, F; Morales, L; Muñoz-Mingarro, M D; Pozuelo, J M; Vicente Orellana, J A

2000-06-01

Aqueous and alcoholic extracts of pods and flowers of Tecoma sambucifolia H.B.K. (Bignoniaceae) ('huarumo') were analysed to determine their anti-inflammatory activity (carrageenan-induced edema test), antinociceptive activity (acetic acid writhing test) and 'in vitro' toxicity in Chinese hamster ovary cells, human hepatome cells and human larynx epidermal carcinoma cells. The cytotoxic effects of both extracts were evaluated by two endpoint systems: neutral red uptake assay and tetrazolium assay. The results showed that all extracts have anti-inflammatory and antinociceptive activity, but the highest potency is that of the alcoholic extracts. There were significant differences in cytotoxicity between extracts and among the response of cells to them. The highest cytotoxicity was noted with the alcoholic extract, and the human hepatome cell line was the most sensitive, especially to the alcoholic extract of flowers. The aqueous pod extract appeared to have the best pharmaco-toxicological profile, since it provided a significant reduction of both pain and inflammation together with the lowest cytotoxicity.
In vivo hypoglycemic, antinociceptive and in vitro antioxidant activities of methanolic bark extract of Crataeva nurvala

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Uddin Jalal

2017-11-01

Full Text Available Objective: To rationalize the folkloric use of hypoglycemic, antinociceptive and antioxidant potentials with phytochemical screening of methanolic bark extract of Crataeva nurvala (C. nurvala in vivo and in vitro. Methods: The collected bark was dried and grinded. The coarse powder was soaked in 2 000 mL of 90% methanol for several days then filtrated. At 40 °C the volume of crude methanolic extract (CME was reduced by a vacuum rotary evaporator, then the aqueous methanol extract was separated into petroleum ether, carbon tetrachloride, and aqueous soluble fractions by Kupchan protocol. Then the extracts were subjected to evaluate in vivo analgesic, hypoglycemic activities in Swiss albino mice model and antioxidant in vitro. Results: In quantitative phytochemical analysis, total phenolic content was found maximum (235.94 mg of GAE/g in aqueous soluble fraction; in case of antioxidant potentials, DPPH free radical scavenging assay showed IC50 value of 9.25 μg/mL exhibited by aqueous soluble fraction in comparison to ascorbic acid (8.27 μg/mL as a reference standard. The CMEs potentially (P < 0.05 reduced the acetic acid-induced writhing and increased (P < 0.05; P < 0.01 latency period in the tail immersion method at a dose dependent manner. The CME significantly reduced blood sugar level of diabetic rat induced by alloxan monohydrate. Conclusions: This study was conducted to validate the extensive use of C. nurvala bark as folk medicine with antinociceptive, hypoglycemic and antioxidant effects. It can be concluded that the bark of C. nurvala possesses good antinociceptive, moderate hypoglycemic and antioxidant activities. However, further chemical and pharmacological revise are needed to elucidate the detail mode of action behind this and identify the responsible active principles.
Neutrophils and the calcium-binding protein MRP-14 mediate carrageenan-induced antinociception in mice

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Rosana L. Pagano

2002-01-01

Full Text Available Background: We have previously shown that the calcium-binding protein MRP-14 secreted by neutrophils mediates the antinociceptive response in an acute inflammatory model induced by the intraperitoneal injection of glycogen in mice.
Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

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Masocha Willias

2010-12-01

Full Text Available Abstract Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p. to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg had no significant activity, minocycline (25 to 100 mg/kg produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg and a selective COX-2 inhibitor, CAY10404 (10 mg/kg had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg or minocycline (50 mg/kg did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH limb paw pressure ratios and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg or
Evaluation of morning glory (Jacquemontia tamnifolia (L.) Griseb) leaves for antioxidant, antinociceptive, anticoagulant and cytotoxic activities.

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Hossain, Mohammad Shahadat; Reza, A S M Ali; Rahaman, Md Masudur; Nasrin, Mst Samima; Rahat, Mohammed Rasib Uddin; Islam, Md Rabiul; Uddin, Md Josim; Rahman, Md Atiar

2018-01-05

The present study was planned to investigate the phytochemical, antioxidant, antinociceptive, anticoagulant and cytotoxic activities of the Jacquemontia tamnifolia (L.) Griseb leaf methanol extract (MExJT) in the laboratory using both in vitro and in vivo methods. Phytochemical values, namely, total phenolic and flavonoid contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect and FeCl3 reducing power effects, were studied by established methods. In vivo antinociceptive activity was performed by acidic acid-induced writhing test and formalin-induced pain test on Swiss albino mice at doses of 125, 250 and 500 mg/kg body weight. The clot lysis and brine shrimp lethality bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities of the plant extract, respectively. Phytochemical screening illustrates the presence of tannins, saponins, flavonoids, gums and carbohydrates, steroids, alkaloids and reducing sugars in the extract. The results showed the total phenolic content (146.33 g gallic acid equivalents/100 g extract) and total flavonoid content (133.33 g quercetin/100 g). Significant (pacetic acid-induced writhing test and formalin-induced pain models in Swiss albino mice with doses of 125, 250 and 500 mg/kg body weight. Significant (panalgesic activity. The results also demonstrate that MExJT has moderate thrombolytic and lower cytotoxic properties that may warrant further exploration.
The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword.

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Chen, Jun; Lariviere, William R

2010-10-01

Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. Copyright 2010 Elsevier Ltd. All rights reserved.
Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

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Mohammad Shah Hafez Kabir

2015-11-01

Full Text Available Objective: To estimate the antidepressant, anxiolytic and antinociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch (S. colocasiifolia leaves. Methods: Swiss albino mice treated with 1% Tween solution, standard drugs and ethanol extract of S. colocasiifolia, respectively, were subjected to the neurological and antinociceptive investigations. The tail suspension test and forced swimming test were used for testing antidepressant activity, where the parameter is the measurement of immobility time. Anxiolytic activity was evaluated by hole board model. Anti-nociceptive potential of the extract was also screened for centrally acting analgesic activity by using formalin induced licking response model and acetic acid induced writhing test was used for testing peripheral analgesic action. Results: Ethanol extract of S. colocasiifolia significantly decreased the period of immobility in both tested models (tail suspension and forced swimming models of antidepressant activity. In the hole board model, there was a dose dependant (at 100 and 200 mg/kg and a significant increase in the number of head dipping by comparing with control (1% Tween solution (P < 0.05 and P < 0.001. In formalin induced licking model, a significant inhibition of pain compared to standard diclofenac sodium was observed (P < 0.05 and P < 0.001. In acetic acid induced test, there was a significant reduction of writhing response and pain in mice treated with leaves extract of S. colocasiifolia at 200 mg/kg body weight (P < 0.05 and P < 0.001. Conclusions: The results proofed the prospective antidepressant, anxiolytic and antinociceptive activities of ethanol extract of S. colocasiifolia leaves.
Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae).

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Damascena, N P; Souza, M T S; Almeida, A F; Cunha, R S; Damascena, N P; Curvello, R L; Lima, A C B; Almeida, E C V; Santos, C C S; Dias, A S; Paixão, M S; Souza, L M A; Quintans Júnior, L J; Estevam, C S; Araujo, B S

2014-01-01

The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 μg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 μg/mL) of lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p < 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms.
Micropropagation, antinociceptive and antioxidant activities of extracts of Verbena litoralis Kunth (Verbenaceae).

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Braga, Virgínia F; Mendes, Giselle C; Oliveira, Raphael T R; Soares, Carla Q G; Resende, Cristiano F; Pinto, Leandro C; Santana, Reinaldo de; Viccini, Lyderson F; Raposo, Nádia R B; Peixoto, Paulo H P

2012-03-01

This work describes an efficient micropropagation protocol for Verbena litoralis and the study of the antinociceptive and antioxidant activities in extracts of this species. For the establishment in vitro, surface-sterilization procedures and PVPP showed high efficiency in fungal-bacterial contamination and phenol oxidation controls. Nodal segments cultivation in MS medium supplemented with 6-benzyladenine (7.5 µM)/α-naphthaleneacetic acid (NAA; 0.005 µM) induced multiple shoots. Elongated shoots were rooted with IAA (0.2 µM). Acclimatization rates were elevated and the plants showed the typical features of this species. The hexanic fraction (HF) of powdered leaves presented a radical scavenging activity with IC(50) = 169.3 µg mL(-1). HF showed a non-dose dependent analgesic activity in the writhing test; its antinociceptive activity in the hot plate test was restricted to 500 mg kg(-1), which is the highest dose. The results of this study showed the potential of tissue culture on conservation and large scale multiplication and confirmed the traditional folk medicine use of V. litoralis.
Anti-inflammatory and antinociceptive activities of methanolic extract from red seaweed Dichotomaria obtusata

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Neivys García Delgado

2013-03-01

Full Text Available The aim of the present work was to investigate the anti-inflammatory and antinociceptive effects of methanolic extract from D. obtusata using classic models in mice (croton oil-induced ear edema and acetic acid-induced writhing and a phospholipase A2 activity test. Qualitative analysis of the chemical composition of seaweed was also determined by extraction with solvents of increasing polarity and precipitation and color tests. Results of qualitative chemical study showed the presence of lactonic and phenolic compounds, reduced carbohydrates, other sugars, flavonoids, fatty compounds, triterpenes and steroids. The extract inhibited mouse ear edema in a dose-dependent manner with an efficacy higher than 90% and a mean effective dose of 4.87µg/ear, while intraperitoneal administration presented a moderate activity. The extract did not inhibit phospholipase A2 activity. In the writhing test, the intraperitoneal administration of the extract showed a strong antinociceptive activity (80.2%, while the oral route showed a lower efficacy. In conclusion, this study demonstrated the anti-inflammatory and antinociceptive effects of methanol extract of D. obtusata in experimental models, suggesting its therapeutic potential in the treatment of peripheral painful and/or inflammatory pathologies.O objetivo do presente trabalho foi investigar os efeitos antiinflamatórios e antinociceptivos de um extrato metanólico de D. obtusata, utilizando modelos clássicos em ratos (teste do edema de orelha induzido por óleo de cróton e teste de contorções induzidas por ácido acético e um teste de atividade de fosfolipase A2. A análise qualitativa da composição química das algas foi também determinada através de extração com solventes de polaridade crescente e testes de precipitação e cor. Os resultados do estudo de química qualitativa mostraram a presença de compostos lactônicos e fenólicos, hidratos de carbono reduzidos e outros a
The validation of Calophyllum brasiliense ("guanandi") uses in Brazilian traditional medicine as analgesic by in vivo antinociceptive evaluation and its chemical analysis.

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Klein-Júnior, Luiz Carlos; Zambiasi, Daniele; Salgado, Giovana Rocha; Delle Monache, Franco; Filho, Valdir Cechinel; de Campos Buzzi, Fátima

2017-07-01

Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test. The amount of 1,2-dimethoxyxanthone was determined in the fraction by UPLC-DAD. CFCB inhibited abdominal constrictions induced by acetic acid up to 97%, with an ID 50 of 9.4 mg/kg (i.p.) and 131.8 mg/kg (p.o.). In the formalin test, CFCB impaired paw licking with an ID 50 of 26.3 mg/kg for the first phase and 27.5 mg/kg for the second phase (i.p.). The painful response evoked by capsaicin and glutamate was significantly reduced (ID 50 26.7 and 47.9 mg/kg, i.p.). The latency time was increased up to 76% at 60 mg/kg (i.p.) in the hot-plate test. 1,2-Dimethoxyxanthone was almost three times more potent (ID 50 27.6 μmol/kg, i.p.) than brasiliensic acid (72.0 μmol/kg) in acetic acid-induced writhing test. The amount of the xanthone was estimated as 92.5 mg/g in the extract. CFCB inhibited the nociceptive response associated to several agents. TRPV1 channels play an important role in the mechanism of action of the fraction. In addition, 1,2-dimethoxyxanthone largely contributes to the antinociceptive effect of CFCB.
Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium corymbosum).

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Torri, Eliane; Lemos, Marivane; Caliari, Vinícius; Kassuya, Cândida A L; Bastos, Jairo K; Andrade, Sérgio F

2007-04-01

Blueberries are among the edible fruits that are recognized best for their potential health benefits. The crude extract from Vaccinium corymbosum was assessed in anti-inflammatory and antinociceptive models. The crude hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg (-1) for all the assays. In the carrageenan test, the crude extract reduced rat paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan, by 42.8 and 46.2%, respectively. With the granulomatous tissue assay dexamethasone displayed significant activity, whereas the blueberry extract was inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%, respectively, were observed for the crude extract, and 61.4% for indometacin. In the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively. Considering that the crude extract of blueberry displayed antinociceptive and anti-inflammatory activity, its consumption may be helpful for the treatment of inflammatory disorders.
Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.

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Miranda, H F; Sierralta, F; Jorquera, V; Poblete, P; Prieto, J C; Noriega, V

2017-02-01

Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ). The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice. STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test. The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.
The Anti-Nociceptive Effect of Aloe. Vera Aqueous Extract in Fructose-Fed Male Rats

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Mohammad Reza Shahraki

2010-05-01

Full Text Available A B S T R A C T Introduction: Aloe Vera extract is used as an anti-inflammatory and anti-bradikinin agent in laboratory animals. The aim of this survey was to evaluate the ant-nociceptive effect of A. Vera aqueous extract in fructose-fed male rats. Methods: Forty-five Wistar-Albino male rats were equally and randomly divided into five groups including sham operated and four test groups. Sham operated group consumed tap water and the test groups consumed fructoseenriched water. Test groups 2, 3 and 4 additionally received, 0, 100, 150 and 200 mg/kg of A. Vera extract, respectively, whereas the other test group received distilled water daily. Tail flick reaction time, serum glucose and oral glucose tolerance test (OGTT were measured. The results were analyzed by SPSS software using ANOVA and Tukey tests. Results were expressed as mean ± SD. Statistical differences were considered significant at p<0.05. Results: The results showed that tail flick reaction time significantly increased in test group 3 which received 200 mg/kg A. Vera extract comparing with that of sham operated group. However, OGTT and serum glucose value were significantly increased in all fructose-fed male rats comparing with those of sham operated group. Discussion: These results indicated that A. Vera aqueous extract can affect tail flick reaction time in fructose-fed male rats. Further studies are required to show the exact mechanism of anti-nociceptive effect of A. Vera extract.

Anti-nociceptive and anti-inflammatory activities of ethanolic flower extract of Newbouldia laevis in mice and rats

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Y Tanko; B Kamba; MI Saleh; K Y Musa; A Mohammed

2008-01-01

Summary: The ethanolic flower extract of Newbouldia laevis was investigated for possible anti-nociceptive and anti-inflammatory effects in rodents. Acetic acid induced writhing (in mice) and formalin tests (in rats) were used to study. The extract caused a significant decrease (P< 0.05), which was not dose a dependent inhibition on acetic acid-induced writhing and the neurogenic pain induced by formalin. The extract at the doses (25, 50 and 100mg/kg) tested showed 59, 71 and 47% inhibition...
Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats.

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Dos Santos, Alain Oliveira; do Val, Danielle Rocha; da Silveira, Felipe Dantas; Gomes, Francisco Isaac Fernandes; Freitas, Hermany Capistrano; de Assis, Ellen Lima; de Almeida, Diana Kelly Castro; da Silva, Igor Iuco Castro; Barbosa, Francisco Geraldo; Mafezoli, Jair; da Silva, Marcos Reinaldo; de Castro Brito, Gerly Anne; Clemente-Napimoga, Juliana Trindade; de Paulo Teixera Pinto, Vicente de Paulo Teixeira; Filho, Gerardo Cristino; Bezerra, Mirna Marques; Chaves, Hellíada Vasconcelos

2018-02-01

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 μg/kg; MC-D1 1 μg/kg, MC-D3 100 μg/kg, MC-D6 1 μg/kg, MC-D7 1 μg/kg, MC-D8 1 μg/kg, MC-D9 10 μg/kg, and MC-H 1 μg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 μL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Bioassay-guided isolation of the antinociceptive compounds motiol and beta-sitosterol from Scorzonera latifolia root extract

Czech Academy of Sciences Publication Activity Database

Acikara, O. B.; Citoglu, G. S.; Dall'Acqua, S.; Özbek, H.; Cvačka, Josef; Žemlička, M.; Šmejkal, K.

2014-01-01

Roč. 69, č. 9 (2014), s. 711-714 ISSN 0031-7144 Institutional support: RVO:61388963 Keywords : natural products * folk medicine * antinociceptive activity Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.052, year: 2014
Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; Braun, Jana M; Steagall, Paulo V M; Keuler, Nicholas S; Heath, Timothy D; Krugner-Higby, Lisa A; Brown, Carolyn S; Paul-Murphy, Joanne R

2013-02-01

To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.
Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones; Sintese e avaliacao preliminar de atividade antinociceptiva de novas isoxazolil-aril-hidrazonas

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Reis, Silvio Leandro Goncalves Bomfim; Almeida, Valderes Moraes de; Almeida, Gleybson Correia de; Boaviagem, Karinna Moura; Mendes, Charles Christophe du Barriere; Faria, Antonio Rodolfo de, E-mail: rodolfo@ufpe.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Ciencias Farmaceuticas; Goes, Alexandre Jose da Silva; Magalhaes, Laudelina Rodrigues; Silva, Teresinha Goncalves da [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Antibioticos

2011-07-01

New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test. (author)
Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

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da Silva Arrigo, Jucicléia; Balen, Eloise; Júnior, Ubirajara Lanza; da Silva Mota, Jonas; Iwamoto, Renan Donomae; Barison, Andersson; Sugizaki, Mario Mateus; Leite Kassuya, Cândida Aparecida

2016-02-17

Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The
Antinociception and anti-inflammation induced by simvastatin in algesiometric assays in mice.

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Miranda, Hugo F; Noriega, Viviana; Olavarria, Loreto; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2011-12-01

Statins, belonging to a well-known drug class used for lowering cholesterol through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also have other pleiotropic properties, such as anti-inflammatory action. The purpose of this study was to evaluate the antinociceptive and anti-inflammatory effects of simvastatin in five models of nociceptive behaviour. Oral gavage administration of simvastatin induced a dose-dependent inhibition of nociception for 1 day in the acetic acid writhing (ED(50) = 5.59 ± 0.07), tail-flick (ED(50) = 112.96 ± 8.00), hot-plate (ED(50) = 134.87 ± 2.20), formalin hind paw (ED(50) = 19.86 ± 1.12 in phase I and 23.30 ± 2.05 in phase II) and orofacial formalin (ED(50) = 5.54 ± 2.74 in phase I and 11.48 ± 1.88 in phase II) tests. However, after 3 days, the values were in the acetic acid writhing (ED(50) = 6.14 ± 0.51), tail-flick (ED(50) = 154 ± 8.88), hot-plate (ED(50) = 136.14 ± 2.94), formalin hind paw (ED(50) = 15.93 ± 0.42 in phase I and 17.10 ± 1.80 in phase II) and orofacial formalin (ED(50) = 6.79 ± 0.66 in phase I and 5.80 ± 1.49 in phase II) tests. This study demonstrated the antinociceptive and anti-inflammatory activities of simvastatin in five models of tonic or phasic pain. These actions seem to be related to the inhibition of cytokine and prostanoid release and stimulation of nitric oxide synthesis. A possible clinical role of simvastatin could be related to the potentially beneficial effects in the neuropathic pain, and by their pleiotropic properties, they could play a clinical role in anti-inflammatory disease. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

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Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.
Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice

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Yousef A. Taher

2015-09-01

Full Text Available Background: Clove oil of Eugenia caryophyllata (Myrtaceae is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache. Aim: The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice. Methods: Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer's-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p. at a dose of 33 mg/kg body weight and the effects were compared with reference drugs. Results: In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acid-induced writhing movements by a maximum of 87.7% (p<0.01 compared with a decrease of 77.7% (p<0.01 in response to aspirin injection (100 mg/kg, intraperitoneal, i.p.. Similarly, in the hot plate test, clove oil significantly increased the reaction latency to pain after 60 min by 82.3% (p<0.05 compared with morphine value of 91.7% (p<0.01. In addition, clove oil and indomethacin produced anti-inflammatory effects, as demonstrated by respectively 50.6% (p<0.05 and 70.4% (p<0.01 inhibition of mouse paw edema induced by carrageenan. Furthermore, clove oil significantly attenuated the hyperthermia induced by yeast at ΔT-max by 2.7°C (p<0.001, and time of peak effects was 30–180 min compared with a paracetamol value ΔT-max of 3.2°C (p<0.001. The estimated i.p. LD50 of clove oil was 161.9 mg/kg. Phytochemical screening of the oil showed the presence of eugenol. Conclusion: The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine.
The Antinociceptive Effects of Hydroalcoholic Extract of Borago Officinalis Flower in Male Rats Using Formalin Test.

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Shahraki, Mohammad Reza; Ahmadimoghadm, Mahdieh; Shahraki, Ahmad Reza

2015-10-01

Borago officinalis flower (borage) is a known sedative in herbal medicine; the aim of the present study was to evaluate the antinociceptive effect of borage hydroalcoholic extract in formalin test male rats. Fifty-six adult male albino Wistar rats were randomly divided into seven groups: Control groups of A (intact), B (saline), and C (Positive control) plus test groups of D, E, F, and G (n=8). The groups D, E, and F received 6.25, 12.5, and 25 mg/kg, Borago officinalis flower hydroalcholic extract before the test, respectively but group G received 25 mg/kg borage extract and aspirin before the test. A biphasic pain was induced by injection of formalin 1%. The obtained data were analyzed by SPSS software ver. 17 employing statistical tests of Kruskal-Wallis and Mann-Whitney. The results were expressed as mean±SD. Statistical differences were considered significant at Ptest groups of D, E, F, and G significantly decreased compared to groups A and B, but this score did not show any difference compared to group C. Moreover, chronic pain behavior score in group G was significantly lower than all other groups. The results indicated that Borago officinalis hydroalcoholic extract affects the acute and chronic pain behavior response in formaline test male rats.
Characterization of phenolic compounds and antinociceptive activity of Sempervivum tectorum L. leaf juice.

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Alberti, Ágnes; Béni, Szabolcs; Lackó, Erzsébet; Riba, Pál; Al-Khrasani, Mahmoud; Kéry, Ágnes

2012-11-01

Sempervivum tectorum L. (houseleek) leaf juice has been known as a traditional herbal remedy. The aim of the present study was the chemical characterization of its phenolic compounds and to develop quantitation methods for its main flavonol glycoside, as well as to evaluate its antinociceptive activity. Lyophilized houseleek leaf juice was studied by HPLC-DAD coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to identify flavonol glycosides, hydroxy-benzoic and hydroxy-cinnamic acids. Ten flavonol glycosides and sixteen phenolic acid compounds were identified or tentatively characterized. Structure of the main flavonol compound was identified by nuclear magnetic resonance spectroscopy. Three characteristic kaempferol glycosides were isolated and determined by LC-ESI-MS/MS with external calibration method, using the isolated compounds as standard. The main flavonol glycoside was also determined by HPLC-DAD. Validated HPLC-DAD and LC-ESI-MS/MS methods were developed to quantify kaempferol-3-O-rhamnosyl-glucoside-7-O-rhamnoside and two other kaempferol glycosides. Antinociceptive activity of houseleek leaf juice was investigated by writhing test of mice. Sempervivum extract significantly reduced pain in the mouse writhing test. Copyright © 2012 Elsevier B.V. All rights reserved.
Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain.

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Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

2016-11-15

Botulinum neurotoxin serotype A (BoNT/A) shows antinociceptive properties, and its clinical applications in pain therapy are continuously increasing. BoNT/A specifically cleaves SNAP-25, which results in the formation of a non-functional SNARE complex, thereby potently inhibiting the release of neurotransmitters and neuropeptides, including those involved in nociception. The aim of the present study was to determine the effects of BoNT/A (300pg/paw) on pain-related behavior and the levels of glial markers and interleukins in the spinal cord and dorsal root ganglia (DRG) after chronic constriction injury (CCI) to the sciatic nerve in rats. Glial activity was also examined after repeated intraperitoneal injection of minocycline combined with a single BoNT/A injection. Our results show that a single intraplantar BoNT/A injection did not influence motor function but strongly diminished pain-related behaviors in naïve and CCI-exposed rats. Additionally, microglial inhibition using minocycline enhanced the analgesic effects of BoNT/A. Western blotting results suggested that CCI induces the upregulation of the pronociceptive proteins IL-18, IL-6 and IL-1β in the ipsilateral lumbar spinal cord and DRG, but no changes in the levels of the antinociceptive proteins IL-18BP, IL-1RA and IL-10 were observed. Interestingly, BoNT/A injection suppressed the CCI-induced upregulation of IL-18 and IL-1β in the spinal cord and/or DRG and increased the levels of IL-10 and IL-1RA in the DRG. In summary, our results suggest that BoNT/A significantly attenuates pain-related behavior and microglial activation and restores the neuroimmune balance in a CCI model by decreasing the levels of pronociceptive factors (IL-1β and IL-18) and increasing the levels of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and DRG. Copyright © 2016 Elsevier B.V. All rights reserved.
Preclinical validation of antinociceptive, antiinflammatory, and antipyretic activities of Cordia martinicensis leave decoction

OpenAIRE

Martínez Hormaza, Ioanna; Victoria Amador, María del Carmen; Brito Álvarez, Gisselle; Morón Rodríguez, Francisco; López Barreiro, Marisol; García Hernández, Ana Ibis; Duménigo González, Abel; Morejón Rodríguez, Zulema; Bacallao Elguea, Yunier; Nossin, Emmanuel

2014-01-01

Introduction: leave decoction of Cordia martinicensis (Jacq.) Roem. & Schult. is commonly used in Dominica, Martinique and St. Lucia to relieve thoracic pain and fever. Objectives: to validate the antiinflammatory, antinociceptive (analgesic), and antipyretic ethnobotanical uses of Cordia martinicensis in experimental animal models. Methods: 30 % aqueous extract of Cordia martinicensis dry leaves was prepared just before use. Analgesic activity was assayed by writhing and tail flick, and anti...
Antinociceptive activities of crude methanolic extract and phases, n-butanolic, chloroformic and ethyl acetate from Caulerpa racemosa (Caulerpaceae

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Everton T. Souza

Full Text Available In this study, we attempted to identify the possible antinociceptive actions of n-butanolic phase, chloroformic phase, ethyl acetate phase and crude methanolic extract obtained from Caulerpa racemosa. This seaweed is cosmopolitan in world, mainly in tropical regions. The n-butanolic, chloroformic, ethyl acetate phases and crude methanolic extract, all administered orally in the concentration of 100 mg/kg, reduced the nociception produced by acetic acid by 47.39%, 70.51%, 76.11% and 72.24%, respectively. In the hotplate test the chloroformic and ethyl acetate phase were activite in this models. In the neurogenic phase on formalin test, were observed that crude methanolic extract (51.77%, n-butanolic phase (35.12%, chloroformic phase (32.70% and indomethacin (32.06% were effective in inhibit the nociceptive response. In the inflammatory phase, only the ethyl acetate phase (75.43% and indomethacin (47.83% inhibited significantly the nociceptive response. Based on these data, we can infer that the ethyl acetate phase shows a significant anti-inflammatory profile, whose power has not yet been determined. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s responsible for the antinociceptive action and also to identify other active principles present in Caulerpa racemosa.
Plasticity of Signaling by Spinal Estrogen Receptor α, κ-Opioid Receptor, and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.

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Liu, Nai-Jiang; Murugaiyan, Vijaya; Storman, Emiliya M; Schnell, Stephen A; Kumar, Arjun; Wessendorf, Martin W; Gintzler, Alan R

2017-11-15

We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR 1 ) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). Differential signaling by mGluR 1 , depending on its activation by membrane estrogen receptor α (mERα; during diestrus) versus glutamate (during proestrus), concomitant with the ebb and flow of spinal dynorphin/KOR signaling, functions as a switch, preventing or promoting, respectively, spinal EM2 antinociception. Importantly, EM2 and glutamate-containing varicosities appose spinal neurons that express MOR along with mGluRs and mERα, suggesting that signaling mechanisms regulating analgesic effectiveness of intrathecally applied EM2 also pertain to endogenous EM2. Regulation of spinal EM2 antinociception by both the nature of the endogenous mGluR 1 activator (i.e., endogenous biased agonism at mGluR 1 ) and changes in spinal dynorphin/KOR signaling represent a novel mechanism for modulating analgesic responsiveness to endogenous EM2 (and perhaps other opioids). This points the way for developing noncanonical pharmacological approaches to pain management by harnessing endogenous opioids for pain relief. SIGNIFICANCE STATEMENT The current prescription opioid abuse epidemic underscores the urgency to develop alternative pharmacotherapies for managing pain. We find that the magnitude of spinal endomorphin 2 (EM2) antinociception not only
Assessment of antinociceptive, antipyretic and antimicrobial activity of Piper cubeba L. essential oil in animal models.

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Mothana, Ramzi; Alsaid, Mansour; Khaled, Jamal M; Alharbi, Naiyf S; Alatar, Abdulrahman; Raish, Mohammad; Al-Yahya, Mohammed; Rafatullah, Syed; Parvez, Mohammad Khalid; Ahamad, Syed Rizwan

2016-03-01

This study was designed to investigate the possible antiniciceptive, antipyretic and antimicrobial activities of the essential oil obtained from the fruits of Piper Cubeba (L.). To assess the antinociceptive and antipyretic activities, three doses (150, 300 and 600 mg/kg, i.p.) were tested in acetic acid-induced abdominal writhing, tail flick reaction and hot-plate and Brewer's yeast-induced hyperpyrexia test models in animals. Moreover, the antimicrobial activity was examined using agar diffusion method and broth micro-dilution assay for minimum inhibitory concentrations (MIC). The Piper Cubeba essential oil (PCEO) showed a marked antinociception (17, 30 and 54%) and an increase in reaction time in mice in the flick tailed and hot-plate tests. The brewer's yeast induced hyperpyrexia was decreased in a dose dependent manner. PCEO also exhibited a strong antimicrobial potential. These findings confirm the traditional analgesic indications of P. cubeba oil and provide persuasive evidence and support its use in Arab traditional medicine.
Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

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Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal

2014-02-01

This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.
Anti-inflammatory and anti-nociceptive activities of methanolic leaf extract of Indigofera cassioides Rottl. Ex. DC.

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Raju Senthil Kumar

2013-01-01

Conclusions: All the results obtained revealed that the extract MEIC showed potent anti-inflammatory and anti-nociceptive activity against all the tested models and the results obtained were comparable with the standards used. The activity of the extract may be due to the presence of terpenoids, flavonoids and other phytochemicals.
Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan

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Shah Syed Muhammad

2012-12-01

may be due to some toxic effect of higher dose. ED50 value for Teucrium stocksianum was calculated as 31.5 ± 1.72415 mg/kg (b.w. Conclusion Our results indicate that there is a lot of variation in the composition of essential oil of Teucrium stocksianum boiss, which may be due to different climatic and experimental conditions. Secondly, the essential oil possesses strong antinociceptive activity and could be used in analgesic preparations especially for topical use.
Chemical composition, acute toxicity, and antinociceptive activity of the essential oil of a plant breeding cultivar of basil (Ocimum basilicum L.).

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Venâncio, Antônio Medeiros; Onofre, Alexandre Sherlley; Lira, Amintas Figueiredo; Alves, Péricles Barreto; Blank, Arie Fitzgerald; Antoniolli, Angelo Roberto; Marchioro, Murilo; Estevam, Charles dos Santos; de Araujo, Brancilene Santos

2011-05-01

Ocimum basilicum L. is an aromatic herb used in Brazil to treat illnesses such as respiratory and rheumatic problems, vomiting, and pain. In the present study, the chemical composition, acute toxicity, and antinociceptive effects of the essential oil (EO) of the cultivar "Maria Bonita" obtained from O. basilicum L. PI 197442 genotype were evaluated in Swiss mice (20-35 g each). Lethal dose to cause 50 % death (LD50) was calculated from a dose-response curve (100-5000 mg/kg body wt.; n = 6) as 532 mg/kg body wt. In the acetic acid-induced writhing test (0.6 % i. p.), EO (50, 100, and 200 mg/kg body wt., n = 8, s. c.) was effective in reducing the abdominal contractions at all doses (48-78 %). In the hot-plate test, EO significantly increased the latency at 50 mg/kg body wt. at all times (37-52 %, n = 8, s. c.). However, the effects of morphine and EO at 50 mg/kg were reverted in the presence of naloxone, an opioid antagonist. In the formalin test, EO significantly reduced paw licking time in the first and second phases of pain at 200 mg/kg body wt. (38 and 75 %, respectively, n = 8, s. c.). The results suggested that the peripheral and central antinociceptive effects of EO are related to the inhibition of the biosynthesis of pain mediators, such as prostaglandins and prostacyclins, and its ability to interact with opioid receptors. © Georg Thieme Verlag KG Stuttgart · New York.

Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

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Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

2016-01-01

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.
Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain.

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Cheing, G L; Hui-Chan, C W

1999-03-01

To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (pTENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.
Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

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Darbon Pascal

2009-11-01

Full Text Available Abstract Background Growing evidence in the literature shows that oxytocin (OT has a strong spinal anti-nociceptive action. Oxytocinergic axons originating from a subpopulation of paraventricular hypothalamic neurons establish synaptic contacts with lamina II interneurons but little is known about the functional role of OT with respect to neuronal firing and excitability. Results Using the patch-clamp technique, we have recorded lamina II interneurons in acute transverse lumbar spinal cord slices of rats (15 to 30 days old and analyzed the OT effects on action potential firing ability. In the current clamp mode, we found that bath application of a selective OT-receptor agonist (TGOT reduced firing in the majority of lamina II interneurons exhibiting a bursting firing profile, but never in those exhibiting a single spike discharge upon depolarization. Interestingly, OT-induced reduction in spike frequency and increase of firing threshold were often observed, leading to a conversion of the firing profile from repetitive and delayed profiles into phasic ones and sometimes further into single spike profile. The observed effects following OT-receptor activation were completely abolished when the OT-receptor agonist was co-applied with a selective OT-receptor antagonist. In current and voltage clamp modes, we show that these changes in firing are strongly controlled by voltage-gated potassium currents. More precisely, transient IA currents and delayed-rectifier currents were reduced in amplitude and transient IA current was predominantly inactivated after OT bath application. Conclusion This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described in vivo.
Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats.

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Nasirinezhad, Farinaz; Gajavelli, Shyam; Priddy, Blake; Jergova, Stanislava; Zadina, James; Sagen, Jacqueline

2015-01-07

The treatment of spinal cord injury (SCI)-induced neuropathic pain presents a challenging healthcare problem. The lack of available robust pharmacological treatments underscores the need for novel therapeutic methods and approaches. Due to the complex character of neuropathic pain following SCI, therapies targeting multiple mechanisms may be a better choice for obtaining sufficient long-term pain relief. Previous studies in our lab showed analgesic effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG), and the mu-opioid peptides endomorphins (EMs), in several pain models. As an alternative to drug therapy, this study evaluated the analgesic potential of these peptides when delivered via gene therapy. Lentiviruses encoding SHG and EM-1 and EM-2 were intraspinally injected, either singly or in combination, into rats with clip compression SCI 2 weeks following injury. Treated animals showed significant reduction in mechanical and thermal hypersensitivity, compared to control groups injected with GFP vector only. The antinociceptive effects of individually injected components were modest, but the combination of EMs and SHG produced robust and sustained antinociception. The onset of the analgesic effects was observed between 1-5 weeks post-injection and sustained without decrement for at least 7 weeks. No adverse effects on locomotor function were observed. The involvement of SHG and EMs in the observed antinociception was confirmed by pharmacologic inhibition using intrathecal injection of either the opioid antagonist naloxone or an anti-SHG antibody. Immunohistochemical analysis showed the presence of SHG and EMs in the spinal cord of treated animals, and immunodot-blot analysis of CSF confirmed the presence of these peptides in injected animals. In a separate group of rats, delayed injection of viral vectors was performed in order to mimic a more likely clinical scenario. Comparable and sustained antinociceptive effects were observed in
Pharmacological effects of a synthetic quinoline, a hybrid of tomoxiprole and naproxen, against acute pain and inflammation in mice: a behavioral and docking study

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Hossein Hosseinzadeh

2017-04-01

Full Text Available Objective(s: In the present study, we investigated the potential anti-nociceptive activity and acute anti-inflammatory effect of a synthetic quinoline compound (2-(4-Methoxyphenylbenzo[h]quinoline-4-carboxylic acid, QC, possessing structural elements of both naproxen and tomoxiprole drugs. Materials and Methods: The anti-nociceptive activity of QC was evaluated using chemical- and thermal-induced nociception models and its acute anti-inflammatory effect was evaluated by xylene-induced ear edema test in mice. Results: QC displayed a dose dependent effect in both acute anti-nociceptive tests (writhing and hot plate. This compound at dose of 6.562 mg/kg showed a high anti-nociceptive effect near equal to diclofenac 5 mg/kg. It also showed high anti-inflammatory effects (less than 6.562 mg/kg comparable to those of reference drugs diclofenac (5 mg/kg and celecoxib (100 mg/kg. Docking study showed that this quinoline derivative could inhibit COX-2 enzyme strongly. Conclusion: QC showed high anti-nociceptive and anti-inflammatory effects comparable to reference drugs and can exert its anti-nociceptive and anti-inflammatory activities through COX-2 inhibition.
Bioactive Polyphenols from the Methanol Extract of Cnicus arvensis (L. Roth Demonstrated Antinociceptive and Central Nervous System Depressant Activities in Mice

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Mahmudur Rahman

2015-01-01

Full Text Available Cnicus arvensis is used by many ethnic groups for inflammation, pain, and other ailments. In this study, reducing sugar, carbohydrate, alkaloid, steroid, tannin, flavonoid, and saponin groups were identified using standard chromogenic method. In high-performance liquid chromatography, vanillic acid and epicatechin were identified in the extract. Antinociceptive test by acetic acid induced writhing inhibition resulted 43.17 and 95.08% inhibition for 100 and 200 mg/kg body weight, comparing with standard diclofenac Na with 74.86% inhibition for 25 mg/kg body weight. In formalin induced paw licking test for antinociceptive activity, the extract inhibited 69.87 and 75.55% licking for 150 and 300 mg/kg body weight comparing with the inhibition (68.56% of diclofenac Na for 10 mg/kg body weight at first phase. At late phase, the extract showed 73.12 and 87.46% licking comparing with licking inhibition (71.69% by diclofenac Na at the same dose. In open field test for CNS depressant activity, the extract showed depression of locomotor activity for 150 and 300 mg/kg body weight comparing with diazepam for 10 mg/kg body weight. All results were statistically significant (P<0.01. The identified polyphenols are reputed for antinociceptive and CNS depressant activity. The present findings support the use of this plant in pain.
Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia

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Shoushtarian, Mehrnaz; Sahinovic, Marko M.; Absalom, Anthony R.; Kalmar, Alain F.; Vereecke, Hugo E. M.; Liley, David T. J.; Struys, Michel M. R. F.

BACKGROUND: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical
Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model

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Claudio Laurido

2012-01-01

Full Text Available N-methyl-D-aspartic acid receptor (NMDAr activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR. D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS and L-erythro-3-hydroxyaspartate (LEHA, among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL and LEHA (100 μg/10 μL in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.
Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats.

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Birol Muhammet, Er; Kocamanoğlu, İsmail Serhat; Bozkurt, Ayhan; Bilge, Sırrı; Çetinoğlu, Erhan Çetin

2016-05-01

Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Animal experimentation. Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (pdexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (pdexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.
Antinociceptive, anti-inflammatory and diuretic properties of Polygonum barbatum (L. Hara var. barbata

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M. Abdul Mazid

Full Text Available The antinociceptive, anti-inflammatory and diuretic properties of the extracts of P. barbatum (L. Hara var. barbata, Polygonaceae, at the doses of 200 and 400 mg/kg body weight, were evaluated in mice/rat models using, respectively, the acetic-acid-induced writhing method, the carrageenan-induced edema test and the Lipschitz method. In the acetic-acid-induced writhing test in mice, all extracts displayed a dose dependent analgesic effect. The most potent analgesic activity was observed with the petroleum ether extract at the dose of 400 mg/kg body weight with an inhibition of writhing response 46.8% compared to 62.2% for the positive control aminopyrine. Petroleum ether extract at the dose of 400 mg/kg body weight also displayed the highest levels of anti-inflammatory activity after 2 h with the 39.3% inhibition of paw edema, and this effect was better than the effect observed by the conventional anti-inflammatory agent phenylbutazone (maximum inhibition of 38.3% after 4 h. All extracts increased urine volume in a dose-dependent manner, and the ethyl acetate extract showed a significant level of diuresis comparable to that of the standard diuretic agent furosemide.
Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

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Carlo Luca Romanò

2012-01-01

Full Text Available Purpose. Chronic low back pain (LBP is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects.
Phytochemical and Antinociceptive, Anti-Inflammatory, and Antioxidant Studies of Smilax larvata (Smilacaceae)

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da Cunha, Joice Maria; Schreiber, Anne Karoline; Ocampos, Fernanda Maria Marins; Barison, Anderson; Miguel, Obdulio Gomes; Miguel, Marilis Dallarmi

2016-01-01

The tea of aerial parts of Smilax larvata Griseb. (Smilacaceae) has been ethnopharmacologically used in Southern Brazil due to its anti-inflammatory action. In this study, ethanolic and organic extracts from aerial parts of S. larvata were phytochemically and pharmacologically characterized. The phytochemical analysis of EtOAc extract of S. larvata revealed the presence of three flavonoids, drabanemoroside, kaempferol 3-O-α-L-rhamnopyranosyl(1→2)-α-L-rhamnopyranoside, and kaempferol, the first two being isolated for the first time in this genus, two phenolic compounds p-hydroxybenzoic acid and p-coumaric acid, and alkaloids. In vitro assays demonstrated a potential antioxidant property of SLG. The treatment with SLG induced a significant reduction of the formalin-evoked flinches in rats, an effect reversed by opioid antagonist naloxone. Treatment with SLG also induced a significant increase in the hot plate latency and a decrease of intestinal motility by 45%. No effect was observed over nociceptive responses induced by a TRPA1 agonist mustard oil or over acetic acid-induced writhing in mice. Together, our data suggested that SLG has an in vivo antinociceptive effect, which seems to be associated with the opioid system activation. These findings support previous claims of medical use of Smilax larvata in the treatment of pain conditions. PMID:28101120
Phytochemical and Antinociceptive, Anti-Inflammatory, and Antioxidant Studies of Smilax larvata (Smilacaceae

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Beatriz Cristina Konopatzki Hirota

2016-01-01

Full Text Available The tea of aerial parts of Smilax larvata Griseb. (Smilacaceae has been ethnopharmacologically used in Southern Brazil due to its anti-inflammatory action. In this study, ethanolic and organic extracts from aerial parts of S. larvata were phytochemically and pharmacologically characterized. The phytochemical analysis of EtOAc extract of S. larvata revealed the presence of three flavonoids, drabanemoroside, kaempferol 3-O-α-L-rhamnopyranosyl(1→2-α-L-rhamnopyranoside, and kaempferol, the first two being isolated for the first time in this genus, two phenolic compounds p-hydroxybenzoic acid and p-coumaric acid, and alkaloids. In vitro assays demonstrated a potential antioxidant property of SLG. The treatment with SLG induced a significant reduction of the formalin-evoked flinches in rats, an effect reversed by opioid antagonist naloxone. Treatment with SLG also induced a significant increase in the hot plate latency and a decrease of intestinal motility by 45%. No effect was observed over nociceptive responses induced by a TRPA1 agonist mustard oil or over acetic acid-induced writhing in mice. Together, our data suggested that SLG has an in vivo antinociceptive effect, which seems to be associated with the opioid system activation. These findings support previous claims of medical use of Smilax larvata in the treatment of pain conditions.
Conceptualizing the Effectiveness of Sustainability Assessment in Development Cooperation

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Jean Hugé

2015-05-01

Full Text Available Sustainability assessment has emerged as a key decision-support process in development cooperation in response to the growing acknowledgement of the impacts of global change. This paper aims at conceptualizing the effectiveness of sustainability assessment as applied in development cooperation, by focusing on the sustainability assessment practice by actors of the official Belgian Development Cooperation. The conceptualization of the effectiveness of sustainability assessment is synthesized in a set of issues and concerns, based on semi-structured interviews. The paper highlights the specificity of sustainability assessment in the development cooperation sector (e.g., through the cultural and discursive compatibility dimensions of assessment in a North-South context. Effectiveness is inherently linked to the expected functions of sustainability assessment in the decision-making process, which include fostering organizational change, shaping contextually adapted framings of sustainability and operationalizing the sustainability transition. These findings highlight the relevance of a discourse-sensitive approach to sustainability assessment if one is to strengthen its credibility and legitimacy.
Healthcare Building Sustainability Assessment tool - Sustainable Effective Design criteria in the Portuguese context

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Castro, Maria de Fátima; Mateus, Ricardo; Bragança, Luís

2017-01-01

Tools and methods to improve current practices and quality in the healthcare building sector are necessary to support decision-making at different building life cycle phases. Furthermore, Healthcare Building Sustainability Assessment (HBSA) Methods are based on criteria organised into different levels, such as categories and indicators. These criteria highlight aspects of significant importance when designing and operating a sustainable healthcare building. To bring more objectivity to the sustainability assessments, the standardisation bodies (CEN and ISO) proposed core indicators that should be used in the evaluation of the environmental, societal and economic performances of buildings. Nevertheless, relying on state of the art analysis, it is possible to conclude that there are aspects of major importance for the operation of healthcare buildings that are not considered in the HBSA methods. Thus, the aim of this paper is to discuss the context of sustainability assessment methods in the field of healthcare buildings and to present a proposal for the incorporation of Sustainable-Effective Design (SED) criteria in a new HBSA method. The used research method is innovative since in the development of the list of sustainability criteria it considers the opinion of main healthcare buildings' stakeholders, the existing healthcare assessment methods and the ISO and CEN standardisation works in the field of the methods to assess the sustainability of construction works. As a result, the proposed method is composed of fifty-two sustainability indicators that cover the different dimensions of the sustainability concept to support decision making during the design of a new or retrofitted healthcare building in urban areas. - Highlights: •A new system to assess the sustainability of healthcare buildings is presented. •We propose a method to develop the list of sustainability indicators for hospitals. •We propose a new concept – Sustainable-Effective Design (SED
Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

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Lazzari, P; Fadda, P; Marchese, G; Casu, G L; Pani, L

2010-06-30

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs. This sparingly soluble terpeno-phenolic compound is not easy to handle and to be formulated in pharmaceutical preparations. The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment. Due to the thermodynamic stability and advantages of microemulsion based systems, the study was focused on the identification of aqueous microemulsion based systems containing Delta(9)-THC. Oil in water Delta(9)-THC microemulsions were individuated through phase diagrams construction, using the non-ionic surfactant Solutol HS15, being this surfactant acceptable for parenteral administration in human. A selected microemulsion samples containing 0.2 wt% of Delta(9)-THC, stable up to 52 degrees C, was successfully assayed on animal models of pain. Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation. The effect has been highlighted in shorter time if compared to a preparation of the same active principle based on previously reported conventional preparation. 2010 Elsevier B.V. All rights reserved.
Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae

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A.F. Biagioni

2012-04-01

Full Text Available The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABAergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA A antagonist bicuculline (40 ng/0.2 µL or saline (0.9% NaCl was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA A receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA A receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.
Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

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Schlichter Rémy

2008-05-01

Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.
Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

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Birol Muhammet Er

2016-06-01

Full Text Available Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. Methods: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L: Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM: Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD: Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D: Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. Results: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others. In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01. Conclusion: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.
Antinociceptive interaction between benfotiamine and resveratrol in capsaicin-induced licking.

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Montiel-Ruiz, Rosa Mariana; Reyes-García, Gerardo; Flores-Murrieta, Francisco; Déciga-Campos, Myrna

2009-01-01

In an attempt to provide more direct evidence concerning the possible antinociceptive effect of resveratrol-benfotiamine combination on neurogenic pain, we investigated whether resveratrol and benfotiamine administered alone or in combination decrease capsaicin induced nociception in mice. Before testing, the animals were placed individually in transparent glass cylinders, 20 cm in diameter, serving as observation chambers. After the adaptation period, 20 microL of capsaicin (1.6 microg/paw) were injected under the skin of the dorsal of the right hind paw. Animals were observed individually for 5 min after capsaicin injection. The amount of time spent licking the injected paw was timed with a chronometer and was considered as indicative of nociception. Animals were pretreated with resveratrol (56.2-177 mg/kg, i.p.), benfotiamine (100-1000 mg/kg, p.o.) and their combinations (11:1, 22:2, 44:4; 88:8 mg/kg benfotiamine:resveratrol). It was observed that resveratrol (ED50 = 104 +/- 8.2 mg/kg) was able to produce more important decrement of capsaicin-induced licking than benfotiamine (ED50 = 529.4 +/- 85.2 mg/kg). In addition, a synergistic interaction was observed between benfotiamine and resveratrol, suggesting that this combination could be useful in neurogenic nociception.

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia.

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Nascimento, Kyria Santiago; Nascimento, Francisco Lucas Faustino do; Silva, Mayara Torquato Lima; Nobre, Camila Bezerra; Moreira, Cleane Gomes; Brizeno, Luiz André Cavalcante; da Ponte, Edson Lopes; Assreuy, Ana Maria Sampaio; Cavada, Benildo Sousa

2016-06-01

Andira anthelmia (tribe Dalbergieae), a plant from Brazilian Amazon, possesses a seed lectin that was purified by affinity chromatography in sepharose-mannose. This novel Dalbergieae lectin, named AAL, agglutinated rabbit erythrocytes treated with trypsin. The hemagglutinating activity of AAL was maintained after incubation at a wide range of temperature (40 to 70 °C) and pH, was shown to be dependent on divalent cations, and was inhibited by d-mannose and d-sucrose. AAL showed an electrophoretic profile in sodium dodecyl sulfate-polyacrylamide gel electrophoresis similar to other lectins of the tribe Dalbergieae, presenting a double band of molecular weight with approximately 20 kDa and other minor bands of 17, 15, and 13 kDa, being the smaller fragment glycosylated. AAL injected by intravenous route in mice showed antinociceptive activity in two behavioral tests (writhing and formalin). In the writhing test induced by acetic acid, AAL showed inhibitory effect at 0.01 mg/kg (68%), 0.1 mg/kg (46%) and 1 mg/kg (74%). In the formalin test, AAL (0.1 mg/kg) inhibited by 48% the licking time in the inflammatory phase, an effect that was recovered by the lectin association with mannose. In conclusion, AAL presents analgesic effect involving the lectin domain via peripheral mechanisms of inflammatory nociception. This activity highlights the importance of lectins as tools to be used for understanding the interaction of protein-carbohydrate in processes associated to inflammatory pain. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Polysaccharide rich fractions from barks of Ximenia americana inhibit peripheral inflammatory nociception in mice Antinociceptive effect of Ximenia americana polysaccharide rich fractions

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Kaira E.S. da Silva-Leite

Full Text Available Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernociception, hot plate, or during 14 days for toxicity assay. The total polysaccharides fraction (TPL-Xa: 8.1% yield presented 43% carbohydrate (21% uronic acid and resulted in two main fractions after chromatography (FI: 12%, FII: 22% yield. FII showed better homogeneity/purity, content of 44% carbohydrate, including 39% uronic acid, arabinose and galactose as major monosaccharides, and infrared spectra with peaks in carbohydrate range for COO- groups of uronic acid. TPL-Xa (10 mg/kg and FII (0.1 and 1 mg/kg presented inhibitory effect in behavior tests that evaluate nociception induced by chemical and mechanical, but not thermal stimuli. TPL-Xa did not alter parameters of systemic toxicity. In conclusion, polysaccharides rich fractions of X. americana barks inhibit peripheral inflammatory nociception, being well tolerated by animals.
Antioxidant, Antinociceptive, and Anti-Inflammatory Activities from Actinidia callosa var. callosa In Vitro and In Vivo

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Jung-Chun Liao

2012-01-01

Full Text Available Actinidia callosa var. callosa has been widely used to treat antipyretic, analgesic, anti-inflammation, abdominal pain, and fever in Taiwan. The aim of this study was to evaluate the antioxidant, antinociceptive, and anti-inflammatory lipopolysaccharide-(LPS-induced nitric oxide (NO production in RAW264.7 macrophages and pawedema induced by λ-carrageenan activities of the methanol extract from A. callosa. In HPLC analysis, the fingerprint chromatogram of ethyl-acetate fraction of A. callosa (EAAC was established. EAAC showed the highest TEAC and DPPH radical scavenging activities, respectively. We evaluated that EAAC and the reference compound of catechin and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Treatment of male ICR mice with EAAC significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of EAAC showed a concentration-dependent inhibition on paw edema development after Carr treatment in mice. Anti-inflammatory mechanisms of EAAC might be correlated to the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, and heme oxygenase-1 (HO-1 in vitro and in vivo. Overall, the results showed that EAAC demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.
The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber).

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Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K; Maloiy, Geoffrey M; Abelson, Klas S P

2014-01-01

The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.
Differential regulation of morphine antinociceptive effects by endogenous enkephalinergic system in the forebrain of mice

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Sun Wei-Zen

2008-09-01

Full Text Available Abstract Background Mice lacking the preproenkephalin (ppENK gene are hyperalgesic and show more anxiety and aggression than wild-type (WT mice. The marked behavioral changes in ppENK knock-out (KO mice appeared to occur in supraspinal response to painful stimuli. However the functional role of enkephalins in the supraspinal nociceptive processing and their underlying mechanism is not clear. The aim of present study was to compare supraspinal nociceptive and morphine antinociceptive responses between WT and ppENK KO mice. Results The genotypes of bred KO mice were confirmed by PCR. Met-enkephalin immunoreactive neurons were labeled in the caudate-putamen, intermediated part of lateral septum, lateral globus pallidus, intermediated part of lateral septum, hypothalamus, and amygdala of WT mice. Met-enkephalin immunoreactive neurons were not found in the same brain areas in KO mice. Tail withdrawal and von Frey test results did not differ between WT and KO mice. KO mice had shorter latency to start paw licking than WT mice in the hot plate test. The maximal percent effect of morphine treatments (5 mg/kg and 10 mg/kg, i.p. differed between WT and KO mice in hot plate test. The current source density (CSD profiles evoked by peripheral noxious stimuli in the primary somatosenstory cortex (S1 and anterior cingulate cortex (ACC were similar in WT and KO mice. After morphine injection, the amplitude of the laser-evoked sink currents was decreased in S1 while the amplitude of electrical-evoked sink currents was increased in the ACC. These differential morphine effects in S1 and ACC were enhanced in KO mice. Facilitation of synaptic currents in the ACC is mediated by GABA inhibitory interneurons in the local circuitry. Percent increases in opioid receptor binding in S1 and ACC were 5.1% and 5.8%, respectively. Conclusion The present results indicate that the endogenous enkephalin system is not involved in acute nociceptive transmission in the spinal cord
Antinociceptive, cytotoxic and antibacterial activities of Cleome viscosa leaves

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Utpal Bose

2011-02-01

Full Text Available The methanol extract of the dried leaves of Cleome viscosa L., Cleomaceae, was investigated for its possible antinociceptive, cytotoxic and antibacterial activities in animal models. The extract produced significant writhing inhibition in acetic acid-induced writhing in mice at the oral doses of 250 and 500 mg/kg body weight (p<0.001 comparable to the standard drug diclofenac sodium at the dose of 25 mg/kg of body weight (p<0.001. The crude extract produced the most prominent cytotoxic activity against brine shrimp Artemia salina (LC50 28.18 μg/mL and LC90 112.20 μg/mL. The extract of C. viscosa L. exhibited significant in vitro antibacterial activity against Staphylococcus saprophyticus, Shigella sonnie, Salmonella typhi, Vibrio cholera, Streptococcus epidermidis, Shigella flexneri and Staphylococcus aureus with the zones of inhibition ranging from 10.76 to 16.34 mm. The obtained results provide a support for the use of this plant in traditional medicine and its further investigation.
Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain

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Dolphin Annette C

2009-08-01

Full Text Available Abstract Background Descending facilitation, from the brainstem, promotes spinal neuronal hyperexcitability and behavioural hypersensitivity in many chronic pain states. We have previously demonstrated enhanced descending facilitation onto dorsal horn neurones in a neuropathic pain model, and shown this to enable the analgesic effectiveness of gabapentin. Here we have tested if this hypothesis applies to other pain states by using a combination of approaches in a rat model of osteoarthritis (OA to ascertain if 1 a role for descending 5HT mediated facilitation exists, and 2 if pregabalin (a newer analogue of gabapentin is an effective antinociceptive agent in this model. Further, quantitative-PCR experiments were undertaken to analyse the α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG in order to assess whether changes in these molecular substrates have a bearing on the pharmacological effects of ondansetron and pregabalin in OA. Results Osteoarthritis was induced via intra-articular injection of monosodium iodoacetate (MIA into the knee joint. Control animals were injected with 0.9% saline. Two weeks later in vivo electrophysiology was performed, comparing the effects of spinal ondansetron (10–100 μg/50 μl or systemic pregabalin (0.3 – 10 mg/kg on evoked responses of dorsal horn neurones to electrical, mechanical and thermal stimuli in MIA or control rats. In MIA rats, ondansetron significantly inhibited the evoked responses to both innocuous and noxious natural evoked neuronal responses, whereas only inhibition of noxious evoked responses was seen in controls. Pregabalin significantly inhibited neuronal responses in the MIA rats only; this effect was blocked by a pre-administration of spinal ondansetron. Analysis of α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG revealed a significant increase in α2δ-1 levels in ipsilateral L3&4 DRG in MIA rats. 5-HT3A subunit mRNA levels were unchanged. Conclusion These data suggest
A novel toxic alkaloid from poison hemlock (Conium maculatum L., Apiaceae): identification, synthesis and antinociceptive activity.

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Radulović, Niko; Dorđević, Nevenka; Denić, Marija; Pinheiro, Mariana Martins Gomes; Fernandes, Patricia Dias; Boylan, Fabio

2012-02-01

2-Pentylpiperidine, named conmaculatin, a novel volatile alkaloid related to coniine was identified from the renowned toxic weed Conium maculatum L. (Apiaceae). The structure of conmaculatin was corroborated by synthesis (8 steps starting from cyclohexanol, overall yield 12%). Conmaculatin's strong peripheral and central antinociceptive activity in mice was observed in a narrow dose range (10-20mg/kg). It was found to be lethal in doses higher than 20mg/kg. Copyright © 2011 Elsevier Ltd. All rights reserved.
Evaluation of anti-nociceptive and anti-inflammatory activities of hydroalcoholic extract derived from root of Apium graveolens L. in mice

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2017-11-01

Full Text Available Background and objectives: Apium graveolens L. (celery has been considered as sedative, analgesic, carminative, antispasmodic and diuretic plant in traditional Iranian medicine. The aim of the present study was to evaluate the anti-nociceptive and anti-inflammatory effect of celery root in mice. Methods: Analgesic effect of celery root was determined by two animal models of hot plate and acetic acid writhing test. Anti-inflammatory potential of the extract was also determined by formalin induced ear edema and xylene induced paw edema tests. Results: The result showed no significant difference between the positive control group and the test group in hot plate test and the most effective dose of celery root was 200 mg/kg, while the frequency of writhings was significantly different in whole test groups in comparison with control group (p
NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.

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de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne

2014-06-01

The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.
Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

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De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

2014-10-15

The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2014 Elsevier GmbH. All rights reserved.
Structure of Agaricus spp. fucogalactans and their anti-inflammatory and antinociceptive properties.

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Komura, Dirce L; Carbonero, Elaine R; Gracher, Ana Helena P; Baggio, Cristiane H; Freitas, Cristina S; Marcon, Rodrigo; Santos, Adair R S; Gorin, Philip A J; Iacomini, Marcello

2010-08-01

Fucogalactans from Agaricus brasiliensis (EPF-Ab) and A. bisporus var. hortensis (EPF-Ah) were prepared via by aqueous extraction and a purification procedure. EPF-Ab had M(w) 19.4 x 10(3)g/mol and EPF-Ah M(w) 31.1 x 10(3)g/mol. EPF-Ab had a (1-->6)-linked alpha-D-Galp main-chain partially substituted in O-2 by non-reducing end-units of alpha-L-Fucp. EPF-Ah had a similar main-chain with O-2 substitution, but was partially methylated at HO-3, as well as having 2.5% non-reducing end-units of beta-D-Gal. In mice, EPF-Ab gave 39% antinociceptive inhibition (ID(50)>100mg/kg) and no anti-inflammatory activity. EPF-Ah also gave an inhibition of 39% at ID(50) 0.33 mg/kg and also inhibited by 61% (ID(50) 5.0mg/kg) total cell migration and by 32% peritoneal capillary permeability, which is related to the anti-inflammatory effect. The small differences in chemical structure in these polysaccharides thus modified their biological activities. (c) 2010. Published by Elsevier Ltd.
Realism and Impartiality: Making Sustainability Effective in Decision-Making.

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Bastons, Miquel; Armengou, Jaume

2017-08-01

There is both individual and collective widespread concern in society about the impact of human activity and the effects of our decisions on the physical and social environment. This concern is included within the idea of sustainability. The meaning of the concept is still ambiguous and its practical effectiveness disputed. Like many other authors, this article uses as a starting point the definition proposed by the World Commission on Environment and Development (Our common future, Oxford University Press, Oxford, 1987), considering it to be a proposal for changing the assessment of the effects of decisions, from at least two perspectives: (1) what effects we should consider and (2) how we should assess them. Based on this double perspective, sustainability is explored as a method for decision-making which both expands the assessment of the consequences, and also provides an objective criterion for such assessment. It will be argued that the idea of sustainability, seen from this perspective, brings to decision-making two qualities which had been partially lost: realism and impartiality. In turn, the criteria for realism and impartiality in decision-making can be used to identify the limitations of some partial approaches to sustainability, which suffer from insufficient realism (emotional altruism), insufficient impartiality (tactical altruism) or both phenomena at once (egoism). The article concludes by demonstrating how realism and impartiality provide the basis for a new form of sustainable decision-making (ethical sustainability), which is dependent on the development of two moral virtues, prudence and benevolence, and which brings practical effectiveness and ethical sense to the concept of sustainability.
Chemical composition and anti-inflamatory, anti-nociceptive and antipyretic activity of rhizome essential oil of Globba sessiliflora Sims. collected from Garhwal region of Uttarakhand

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Ravendra Kumar

2017-07-01

Full Text Available Background & Aim: Family Zingiberaceae is worldwide in distribution. Plants of the zingiberaceae family are used in traditional herbal folk medicine besides their uses in spices, cosmetic, ornamental, food preservatives etc. In Uttarakhand the herbs grow from sub-tropical to temperate region. Globba sessiliflora Simsrhizomes were collected at maturity stage in November from Garhwal region of Uttarakhand, India. In present communication the medicinal use of various zingiberaceous herb provoked us to study the chemical diversity and pharmacological activity determination of this important traditional herb. Experimental: The essential oil was extracted using hydrodistillation method and analyzed by GC-MS. Anti-inflamatory, anti-nociceptive and antipyretic activities of essential oil were experimently determined using mice model. Results: The major compounds identified were β-eudesmol (27.6%, (E-β-caryophyllene (24.3%, α-humulene (3.0%, (6E-nerolidol (4.1%, caryophyllene oxide (9.7%, γ-eudesmol (6.4% and τ-muurolol (8.3% besides other minor constituents. Essential oil of G. sessiliflora rhizome showed good anti-inflamatory, anti-nociceptive and antipyretic activities at the dose level of 100 mg/kg body weight. The oral administration of the essential oil exhibited no toxicity at 400, 600 and 800 mg/kg b.wt. concentration. Ibuprofen, indomthacin and paracetamol were used as standard drugs for comparison. Recommended applications/industries: G. sessiliflora essential oil can be used as herbal remedy for its nontoxicityanti-inflamatory, anti-nociceptive and antipyretic activities.
[Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment].

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Hui, Jianfeng; Li, Tao; Du, Zhi; Song, Jichang

2011-12-01

This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks.
Evaluation of anti-inflammatory, anti-nociceptive, and anti-arthritic activities of Indian Apis dorsata bee venom in experimental animals: biochemical, histological, and radiological assessment.

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Nipate, S S; Hurali, Prakash B; Ghaisas, M M

2015-04-01

Traditionally venoms are used from thousands of years to treat pain, inflammation, and arthritis. In Ayurveda "Suchika Voron" and "Shodhona" were practiced against pain. In the present study, venom composition of the Indian honeybee Apis florea (AF), Apis dorsata (AD), and Apis cerana indica (AC) were analyzed using electrophoresis (SDS-PAGE). This venom analysis was used to shed light upon the correlation in structure and the venom composition among the three species in Indian fields. Among the three species, Indian Apis dorsata bee venom (ADBV) is evaluated for an anti-inflammatory, anti-nociceptive activity, and antiarthritic activity in different animal models. The effect of ADBV is revealed for its anti-arthritic activity in the FCA- and CIA-induced arthritis model in male Wistar rats. The immunosuppressant action of ADBV was studied by hemagglutination antibody titer. It has been found that ADBV possesses anti-inflammatory and antinociceptive activities. In FCA- and CIA-induced arthritis, ADBV able to decrease rheumatoid factor, pain perception parameters, C-reactive protein, erythrocytes sedimentation rate, urinary hydroxyproline, serum transaminase level, and serum nitric oxide level when compared with diseased control arthritic rats. IL-6, TNF-α level was found to be decrease by ADBV treatment in collagen induced arthritis model. Thus this study confirmed the scientific validation behind utilization of venom in Indian Apis dorsata bees in arthritis and inflammatory diseases which has been not reported till date.
Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

Lillesø, J; Hammer, N A; Pedersen, J L

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....
Priority for sustainability. Study of the effects on investment climate

International Nuclear Information System (INIS)

2007-12-01

The Dutch cabinet has been asked to make sure that sustainable electricity plants can be connected to the grid with high priority. By request of the Dutch Ministry of Economic Affairs, the effects on the investment climate have been examined (both for sustainable and conventional) if priority (with regard to connection and transport) is given to sustainable generated electricity. Five models for priority for sustainable have been defined, i.e. (1) Sustainable is only given priority on the waiting list for connection; (2) Connect sustainable immediately, but no priority for transport; (3) Connect sustainable immediately and priority granted in transport; (4) Connect sustainable and conventional immediately, no priority for transport; (5) Connect sustainable and conventional immediately and give priority in transport to sustainable. [mk] [nl
Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.

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Tuboly, Gabor; Mecs, Laszlo; Benedek, György; Horvath, Gyöngyi

2009-04-01

1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.
Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats

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Amir Erfanparast

2015-08-01

Full Text Available Objective: Crocin and safranal are the main components of saffron, and have many biological functions such as anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of crocin, safranal, morphine, diclofenac and naloxone in combined and separately on formalin-induced orofacial pain in rats. Materials and Methods: Subcutaneous injection of a diluted formalin solution (50 µl, 1.5% into the upper lip region produced a biphasic pattern of pain response (a neurogenic phase: 0-3 min and an inflammatory phase: 15-33 min. The time each animal spent face rubbing with ipsilateral forepaw was recorded and considered as an index of nociception Results: Intraperitoneal injections of crocin (12.5 and 25 mg/kg, safranal (0.25 and 0.5 mg/kg, diclofenac (5 and 10 mg/kg and morphine (1 and 2 mg/kg suppressed the second phase of pain. The second phase of pain was also reduced when low (ineffective doses of crocin (6.25 mg/kg and safranal (0.125 mg/kg were co-administered with low doses of diclofenac (2.5 mg/kg and morphine (0.5 mg/kg. The more antinociceptive effects were observed when the medium doses of the above-mentioned chemicals used together. Naloxone prevented morphine-induced antinociception, but did not inhibit the suppressive effects of crocin and safranal. Safranal at a high dose (0.5 mg/kg suppressed locomotor activity. Conclusion: The present results showed antinociceptive effects for crocin and safranal in inflammatory pain. Opioid receptors may not be involved in the antinociceptive effect of crocin and safranal. Crocin and safranal increased diclofenac-induced antinociception.

Determinants of Sustainability and Organisational Effectiveness in Non-Profit Organisations

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Chux Gervase Iwu

2015-07-01

Full Text Available This case study investigates the criteria for organizational effectiveness in non-profit organizations (NPOs with the aim to determine how the elements of sustainability fit within the criteria. To achieve this, the study utilized the research questions: “what criteria do NPOs use to evaluate their effectiveness?” and “how is sustainability embedded in NPO effectiveness?” The research design was interpretivist, adopting focus group interviews to obtain data. Specifically, two focus group interviews were held with the top management of an NPO which revealed that both financial and non-financial criteria were equally essential for NPO effectiveness. This finding is consistent with the literature, although it contradicts the initial assumption of the study that NPO effectiveness was based more on non-financial criteria than financial criteria. The study also found that the effectiveness of an NPO should be viewed in two ways: firstly, “the full achievement of its mandate” and, secondly, “the ability to run business projects to cover cost.” It also emerged that both the ability to cover costs and the achievement of a mandate should be done in a sustainable manner (a sustainable manner is seen as one that is harmonious with the natural and the socio-political environment. The results of this paper present a practical case for the management of NPOs by reiterating that the full achievement of the NPO mandate and the successful running of social projects to generate funds for sustainability are key elements of effectiveness. Given the essential role that NPOs play in developing countries, this study has provided the foundation for more widespread enquiry into the sustainability and effectiveness of NPOs.
Analgesic effects of stem bark extracts of Trichilia monadelpha (Thonn.) JJ De Wilde.

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Woode, Eric; Amoh-Barimah, Ama Kyeraa; Abotsi, Wonder Kofi Mensah; Ainooson, George Kwaw; Owusu, George

2012-01-01

Various parts of Trichilia monadelpha (Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models. PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test. HAE, EAE, and PEE, each at doses of 10-100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine. The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K+ channels while that of EAE and PEE involve the muscarinic cholinergic system.
The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

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Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

2017-08-01

Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.
The analgesic effect of clonixine is not mediated by 5-HT3 subtype receptors.

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Paeile, C; Bustamante, S E; Sierralta, F; Bustamante, D; Miranda, H F

1995-10-01

1. The analgesic effect of clonixinate of L-lysine (Clx) in the nociceptive C-fiber reflex in rat and in the writhing test in mice is reported. 2. Clx was administered by three routes, i.v., i.t. and i.c.v., inducing a dose-dependent antinociception. 3. The antinociceptive effect of Clx was 40-45% with respect to the control integration values in the nociceptive C-fiber reflex method. 4. The writhing test yielded ED50 values (mg/kg) of 12.0 +/- 1.3 (i.p.), 1.8 +/- 0.2 (i.t.) and 0.9 +/- 0.1 (i.c.v.) for Clx administration. 5. Ondansetron was not able to antagonize the antinociception response of Clx in the algesiometric tests used. 6. Chlorophenilbiguanide did not produce any significative change in the analgesic effect of Clx in the nociceptive C-fiber reflex method. 7. It is suggested that the mechanism of action of the central analgesia of Clx is not mediated by 5-HT3 subtype receptors.
Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

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Edson N. Santos

2011-06-01

Full Text Available Cariniana rubra Miers (Lecythidaceae, popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (β-sitosterol, stigmasterol, pentacyclic triterpenes (α- and β-amyrin as a mixture, arjunolic acid, a phytosterol glycoside (sitosterol 3-O-β-D-glucopyranoside, and triterpenoid saponins (28-β-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-β-glucopyranosyl arjunolic acid and 28-O-[α-L-Rhamnopyranosyl-(1→2-β-glucopyranosyl]-23- O-acetyl arjunolic acid were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.Cariniana rubra Miers (Lecythidaceae, popularmente conhecido como
Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

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Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

2005-01-01

As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects.
Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

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Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
The Effect of Implementation of Education for Sustainable Development in Swedish Compulsory Schools--Assessing Pupils' Sustainability Consciousness

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Olsson, D.; Gericke, N.; Chang Rundgren, S.-N.

2016-01-01

During the past decade, numerous schools in Sweden have implemented education for sustainable development (ESD) as an explicit guiding approach in teaching. In this paper, we investigate the effect of this approach in comparison with that of pupils taught in ordinary schools. Accordingly, we introduce the concept of sustainability consciousness to…
Effect of pilocarpine on the formalin-induced orofacial pain in rats

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Esmaeal Tamaddonfard

2012-06-01

Full Text Available In this study, the effects of subcutaneous (SC injection of pilocarpine (a cholinomimetic agent and atropine (a muscarinic receptors antagonist were investigated on a tonic model of orofacial pain in rats. The contribution of the endogenous analgesic opioid system was assessed using naloxone (an opioid receptors antagonist. Tonic orofacial pain was induced by SC injection of a diluted formalin solution (1%, 50 μL in the right upper lip, and the time spent face rubbing was measured in five min blocks for 1 h. Formalin induced a biphasic (first phase: 0-5 min and second phase: 15-35 min pain response. Pilocarpine significantly (P < 0.05 suppressed both phases of orofacial pain. Atropine did not have any effect and naloxone non-significantly increased the intensity of pain when used alone. In the pre-injection examinations, atropine prevented, but naloxone did not reverse the antinociceptive effect of pilocarpine. The results indicated that SC injection of formalin in the orofacial region induced a marked biphasic pain. Pilocarpine via muscarinic cholinergic receptors produced antinociceptive effect in the orofacial formalin-induced pain. The endogenous opioid analgesic system may not have a role in pilocarpine-induced antinociception.
Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

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Luis Alfonso Moreno-Rocha

2016-11-01

Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P 0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.
Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects.

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Amin, Bahareh; Hosseinzadeh, Hossein

2016-01-01

For many centuries, seeds of Nigella sativa (black cumin), a dicotyledon of the Ranunculaceae family, have been used as a seasoning spice and food additive in the Middle East and Mediterranean areas. Traditionally, the plant is used for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and gastrointestinal disturbances. The literature regarding the biological activities of seeds of this plant is extensive, citing bronchodilative, anti-inflammatory, antinociceptive, antibacterial, hypotensive, hypolipidemic, cytotoxic, antidiabetic, and hepatoprotective effects. The active ingredients of N. sativa are mainly concentrated in the fixed or essential oil of seeds, which are responsible for most health benefits. This review will provide all updated reported activities of this plant with an emphasis on the antinociceptive and anti-inflammatory effects. Results of various studies have demonstrated that the oil, extracts, and their active ingredients, in particular, thymoquinone, possess antinociceptive and anti-inflammatory effects, supporting the common folk perception of N. Sativa as a potent analgesic and anti-inflammatory agent. Many protective properties are attributed to reproducible radical scavenging activity as well as an interaction with numerous molecular targets involved in inflammation, including proinflammatory enzymes and cytokines. However, there is a need for further investigations to find out the precise mechanisms responsible for the antinociceptive and anti-inflammatory effects of this plant and its active constituents. Georg Thieme Verlag KG Stuttgart · New York.
Wrong effects of apparent sustainable solutions. The Dutch impact on global biodiversity

International Nuclear Information System (INIS)

Rood, T.; Alkemade, R.

2005-01-01

What is the value of sustainable development in a specific country if imported products have negative effects in the country from where those products were imported. Apparently sustainable solutions in one's own country might have negative effects somewhere else, sooner or later. A clear picture of the ecological claim of a country is one of the methods to find the right way towards a sustainable future [nl
Mechanisms Underlying the Antinociceptive, Antiedematogenic, and Anti-Inflammatory Activity of the Main Flavonoid from Kalanchoe pinnata

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Raquel Teixeira Ferreira

2014-01-01

Full Text Available Kalanchoe pinnata (KP is popularly used for treating inflammatory diseases. This study investigated the antinociceptive, antiedematogenic, and anti-inflammatory potential of the subcutaneous administration of KP flower aqueous extract (KPFE, its ethyl acetate (EtOAcF and butanol (BuOHF fractions, and the main KP flavonoid [quercetin 3-O-α-L-arabinopyranosyl (1→2 α-L-rhamnopyranoside] (KPFV in mice, as well as its possible mechanisms of action. KPFE (30–300 mg/kg and KPFV (1–10 mg/kg inhibited the acetic acid-induced writhing (ID50 = 164.8 and 9.4 mg/kg, resp.. KPFE (300 mg/kg, EtOAcF (12 mg/kg, BuOHF (15 mg/kg, or KPFV (0.3–3.0 mg/kg reduced leukocyte migration on carrageenan-induced pleurisy (ID50 = 2.0 mg/kg for KPFV. KPFE (3–30 mg/kg and KPFV (0.3–3.0 mg/kg reduced the croton oil-induced ear edema (ID50 = 4.3 and 0.76 mg/kg, resp.. KPFE and KPFV reduced the TNF-α concentration in the pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited COX-1 (IC50 = 22.1 μg/mL and COX-2 (IC50 > 50 μg/mL. The selectivity index (COX-1IC50/COX-2IC50 was <0.44. These results indicate that KPFE and KPFV produced antinociceptive, antiedematogenic, and anti-inflammatory activities through COX inhibition and TNF-α reduction, revealing that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of the plant.
Mechanisms Underlying the Antinociceptive, Antiedematogenic, and Anti-Inflammatory Activity of the Main Flavonoid from Kalanchoe pinnata

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Ferreira, Raquel Teixeira; Coutinho, Marcela Araújo Soares; Malvar, David do Carmo; Costa, Elson Alves; Florentino, Iziara Ferreira; Costa, Sônia Soares; Vanderlinde, Frederico Argollo

2014-01-01

Kalanchoe pinnata (KP) is popularly used for treating inflammatory diseases. This study investigated the antinociceptive, antiedematogenic, and anti-inflammatory potential of the subcutaneous administration of KP flower aqueous extract (KPFE), its ethyl acetate (EtOAcF) and butanol (BuOHF) fractions, and the main KP flavonoid [quercetin 3-O-α-L-arabinopyranosyl (1 → 2) α-L-rhamnopyranoside] (KPFV) in mice, as well as its possible mechanisms of action. KPFE (30–300 mg/kg) and KPFV (1–10 mg/kg) inhibited the acetic acid-induced writhing (ID50 = 164.8 and 9.4 mg/kg, resp.). KPFE (300 mg/kg), EtOAcF (12 mg/kg), BuOHF (15 mg/kg), or KPFV (0.3–3.0 mg/kg) reduced leukocyte migration on carrageenan-induced pleurisy (ID50 = 2.0 mg/kg for KPFV). KPFE (3–30 mg/kg) and KPFV (0.3–3.0 mg/kg) reduced the croton oil-induced ear edema (ID50 = 4.3 and 0.76 mg/kg, resp.). KPFE and KPFV reduced the TNF-α concentration in the pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited COX-1 (IC50 = 22.1 μg/mL) and COX-2 (IC50 > 50 μg/mL). The selectivity index (COX-1IC50/COX-2IC50) was <0.44. These results indicate that KPFE and KPFV produced antinociceptive, antiedematogenic, and anti-inflammatory activities through COX inhibition and TNF-α reduction, revealing that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of the plant. PMID:25580151
Effects of Corporate Sustainability on Established Brand : the case of IKEA

OpenAIRE

Gbanabila, Yenimi

2014-01-01

The emergence of Sustainable Development as an alternative approach to changing unsustainable behaviour in today’s business practices to save the planet towards a sustainable society is shifting branding paradigm from the “what of the commodity to the how of shared values”. For marketers responding to this changing paradigm to maintain competitive in today’s market sustainable branding is gaining attention in today’s business practices. But does sustainable practice have effects on branding i...
Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

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Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

2017-01-01

Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID
Blood-brain transfer and antinociception of linear and cyclic N-methyl-guanidine and thiourea-enkephalins

DEFF Research Database (Denmark)

Verbeken, Mathieu; Wynendaele, Evelien; Mauchauffee, Elodie

2015-01-01

Enkephalins are active in regulation of nociception in the body and are key in development of new synthetic peptide analogs that target centrally located opioid receptors. In this study, we investigated the in vivo blood–brain barrier (BBB) penetration behavior and antinociceptive activity of two...... cyclic enkephalin analogs with a thiourea (CycS) or a N-methyl-guanidine bridge (CycNMe), and their linear counterparts (LinS and LinNMe) in mice, as well as their in vitro metabolic stability. 125I-LinS had the highest blood–brain clearance (K1 = 3.46 μL/g min), followed by 125I-LinNMe, 125I...
The effect of natural resources on a sustainable development policy: The approach of non-sustainable externalities

International Nuclear Information System (INIS)

Schilling, Markus; Chiang Lichun

2011-01-01

The debate about the importance of non-renewable resources for economic development between optimists and pessimists shows that the extensive depletion of non-renewable resources, particularly oil, along with a higher level of consumption could have a significant impact on the economic development of future generations. Based on this debate, this paper proposes criteria under which the depletion of non-renewable resources would create excess costs for future generations. Therefore, this paper aims to answer the question 'What will be the impact of the depletion of non-renewable resources on sustainable economic development?' Accordingly, a sustainable development policy appears feasible by minimizing non-sustainable externalities which derive from future externalities that weigh the benefits from a previous employment of natural resources. The research based on qualitative analysis clarifies the reasons for and the extents of taking sustainability into account as well as points to difficulties of implementing policies to time the transition towards a sustainable economic development. Finally, the research shows the implications of this approach for environmental degradation, the depletion of non-renewable resources and energy production. - Research Highlights: →Economic development will more or less smoothly switch to the use of renewable substitutes. →The transition towards a sustainable use of resources may inherit costs for future generations. →Non-sustainable externalities show the future costs of excessive resource depletion. →The approach aims to take the long-term global effects of resource substitution into account.
Effective Strategies for Sustaining Professional Learning Communities

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Bennett, Patricia R.

2010-01-01

Professional Learning Communities (PLCs), in which educators work collaboratively to improve learning for students, need effective strategies to sustain them. PLCs promote continuous improvement in student learning and build academic success with increased teacher expertise. Grounded in organizational systems theory, participative leadership…
Measuring the effect of Sustainable Public Procurement

NARCIS (Netherlands)

Zijp MC; Kok L; Valk E de; DMG; M&V; M&V

2018-01-01

Many purchasing services of the Dutch local and central governments, aim to include the effects of products and services on human health and the environment in the procurement process. Sustainable procurement (SP) encompasses more than just price and quality considerations. SP can result, for

Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

Directory of Open Access Journals (Sweden)

Lucia Marseglia

2015-01-01

Full Text Available Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.
Eel calcitonin binding site distribution and antinociceptive activity in rats

International Nuclear Information System (INIS)

Guidobono, F.; Netti, C.; Sibilia, V.; Villa, I.; Zamboni, A.; Pecile, A.

1986-01-01

The distribution of binding site for [ 125 I]-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing [ 125 I]-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain
Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid.

Science.gov (United States)

Park, Jae Gwang; Kim, Seung Cheol; Kim, Yun Hwan; Yang, Woo Seok; Kim, Yong; Hong, Sungyoul; Kim, Kyung-Hee; Yoo, Byong Chul; Kim, Shi Hyung; Kim, Jong-Hoon; Cho, Jae Youl

2016-01-01

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.
Antinociceptive and antioxidant potential of the crude ethanol extract of the leaves of Ageratum conyzoides grown in Bangladesh.

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Hossain, Hemayet; Karmakar, Utpal Kumar; Biswas, Subrata Kumar; Shahid-Ud-Daula, A F M; Jahan, Ismet Ara; Adnan, Tarek; Chowdhury, Anusua

2013-07-01

Ageratum conyzoides Linn. (Asteraceae) is an annual herbaceous plant with a long history of traditional medicinal and agricultural uses; it is usually grown in the northeast part of Bangladesh. The ethanol extract of the plant leaves was evaluated for preliminary phytochemical screening with its antinociceptive and antioxidant activities. The preliminary phytochemical analysis was performed on the basis of standard procedures. The analgesic activity of the extract was investigated using the acetic acid-induced writhing method in mice. Five complementary tests such as DPPH free radical scavenging, nitric oxide (NO) scavenging, reducing power, Fe(++) ion chelating ability and total phenolic content were used for determining antioxidant activities. The results of preliminary phytochemical analysis showed the presence of alkaloids, reducing sugars, saponins, gums, steroids, tannins and flavonoids. The extract possessed a significant dose-dependent DPPH free radical scavenging activity with an IC50 value of 18.91 μg/ml compared to ascorbic acid (IC50: 2.937 μg/ml) and butylated hydroxyanisole (IC50: 5.10 μg/ml). The IC50 value of the extract for NO scavenging (41.81 μg/ml) was also found to be significant compared to the IC50 value of ascorbic acid (37.93 μg/ml). Moreover, the extract showed reducing power activity and Fe(++) ion chelating ability. The total phenolic amount was also calculated as quite high (378.37 mg/g of gallic acid equivalents) in the crude ethanol extract. Therefore, the obtained results tend to suggest the antinociceptive and antioxidant activities of the ethanol extract of the plant leaves and justify its use in folkloric remedies.
The employment effects of sustainable development policies

International Nuclear Information System (INIS)

McNeill, Judith M.; Williams, Jeremy B.

2007-01-01

This paper argues that it is time for ecological economists to bring the employment impacts of sustainable development policies to the forefront of the research agenda. Important conservation efforts continue to founder because of their perceived employment effects. The paper examines the evidence on the employment impacts of sustainable development policies and argues that maintaining or even increasing employment depends critically on appropriate policy design and attention to the political economy of implementation of policies. The paper concludes that a better understanding of these issues, fair labour market and structural adjustment programs, and especially forward planning to anticipate problem areas, must replace the piecemeal, 'knee-jerk' reactions to environmental issues, such as were evident in Australia during the last federal election. (author)
Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks.

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Kucyi, Aaron; Salomons, Tim V; Davis, Karen D

2013-11-12

Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual's tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain-cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual's tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG-DMN structural connectivity and more dynamic resting state PAG-DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.
Involvement of 5-HT(2) serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome.

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de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Ferreira, Célio Marcos Dos Reis; Coimbra, Norberto Cysne

2006-09-01

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.
Effect of ripple loads on sustained-load cracking in titanium alloys

International Nuclear Information System (INIS)

Pao, P.S.; Meyn, D.A.; Bayles, R.A.; Feng, C.R.; Yoder, G.R.

1995-01-01

In the present paper, the authors have extended their study on the effect of the ripple loads on the sustained-load cracking (SLC) behavior of two titanium alloys, Ti-6Al-4V (an α-β alloy) and Ti-15V-3Cr-3Al-3Sn (a β-α alloy), in an ambient air environment. The methodology which has been used successfully to treat ripple effects on stress-corrosion cracking (SCC) is employed again to address the influence of ripple loads on sustained-load cracking. Ripple loads can significantly reduce the apparent sustained load cracking resistance of titanium alloys in a relatively benign environment such as ambient air. For a ripple-load amplitude equal to 5% of the sustained load, the ripple-load cracking thresholds (K IRLC ) of beta-annealed Ti-6Al-4V and Ti-15V-3Cr-3al-3Sn are less than half of the respective sustained-load cracking thresholds (K ISLC ). The extent of ripple-load degradation for these alloys in ambient air -- relative to K ISLC , were found comparable to those observed in a much more aggressive 3.5% NaCl aqueous solution
Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

Science.gov (United States)

2012-01-01

Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis increased HPV during
Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

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Ketabchi Farzaneh

2012-01-01

Full Text Available Abstract Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV optimizes gas exchange during local acute (0-30 min, as well as sustained (> 30 min hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate, and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA, a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS, decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc. This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis
Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction.

Science.gov (United States)

Ketabchi, Farzaneh; Ghofrani, Hossein A; Schermuly, Ralph T; Seeger, Werner; Grimminger, Friedrich; Egemnazarov, Bakytbek; Shid-Moosavi, S Mostafa; Dehghani, Gholam A; Weissmann, Norbert; Sommer, Natascha

2012-01-31

Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The
Micropropagation, antinociceptive and antioxidant activities of extracts of Verbena litoralis Kunth (Verbenaceae

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Virgínia F. Braga

2012-03-01

Full Text Available This work describes an efficient micropropagation protocol for Verbena litoralis and the study of the antinociceptive and antioxidant activities in extracts of this species. For the establishment in vitro, surface-sterilization procedures and PVPP showed high efficiency in fungal-bacterial contamination and phenol oxidation controls. Nodal segments cultivation in MS medium supplemented with 6-benzyladenine (7.5 µM/α-naphthaleneacetic acid (NAA; 0.005 µM induced multiple shoots. Elongated shoots were rooted with IAA (0.2 µM. Acclimatization rates were elevated and the plants showed the typical features of this species. The hexanic fraction (HF of powdered leaves presented a radical scavenging activity with IC50 = 169.3 µg mL-1. HF showed a non-dose dependent analgesic activity in the writhing test; its antinociceptive activity in the hot plate test was restricted to 500 mg kg-1, which is the highest dose. The results of this study showed the potential of tissue culture on conservation and large scale multiplication and confirmed the traditional folk medicine use of V. litoralis.Este trabalho descreve um protocolo eficiente de micropropagação para Verbena litoralis e estuda as atividades antinociceptiva e antioxidante de extratos desta espécie. Para o estabelecimento in vitro, os procedimentos de desinfecção e o PVPP mostraram alta eficiência no controle da contaminação por fungos e bactérias e da oxidação fenólica. O cultivo de segmentos nodais em meio MS suplementado com 6-benziladenina (7,5 µM e ácido α-naftalenoacético (ANA; 0,005 µM induziu múltiplos brotos. Brotos alongados foram enraizados com AIA (0,2 µM. As taxas de aclimatização foram elevadas e as plantas apresentaram características típicas da espécie. A fração hexânica (FH de folhas trituradas apresentou atividade sequestradora de radicais livres com IC50 = 169,3 µg mL-1. A FH mostrou atividade analgésica não dose-dependente no teste das contor
Effect of yogic education system and modern education system on sustained attention.

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Rangan, R; Nagendra, H R; Bhatt, Ramachandra

2009-01-01

Sustained attention is a vital function mediated by the right frontoparietal cortex. The Six Letter Cancellation Task (SLCT) measures sustained attention. Development of sustained attention in a yoga-based education system compared to a modern one is the theme of the present study. To compare the effectiveness of the Modern Education System (MES) and the Gurukula Education System (GES) in developing sustained attention. Forty nine boys (11-13 years) were selected from two residential schools, one MES and the other GES, providing similar ambiance and daily routines. The boys were matched for age and socioeconomic status. The GES educational program is based around integrated yoga modules while the MES provides a conventional modern education program. Sustained attention was assessed using the SLCT at the start and end of an academic year. Within groups, the pre-post test differences were significant for both groups. However, the between groups result showed improvement in the GES group compared to the MES group at a P < 0.001 significance level. The study suggests that both MES and GES improve sustained attention in school boys, but GES is more effective.
Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

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Hui-Zhong Wen

2017-06-01

Full Text Available Background: Transcranial direct current stimulation (tDCS is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters.Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1 on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia.Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI, we measured pain thresholds before and after anodal-tDCS (A-tDCS using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models.Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS and contralateral-tDCS (con-tDCS produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats.Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical
Building Corporate Reputation through Sustainable Entrepreneurship: The Mediating Effect of Ethical Behavior

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Mª del Mar Ramos-González

2017-09-01

Full Text Available This article investigates how a management approach based on sustainable entrepreneurship can positively affect corporate reputation. The analysis showed that this effect is enhanced by the mediating effect of good governance based on ethical behavior. The empirical study was conducted using data for 104 large Spanish firms defined as sustainable by the Corporate Reputation Business Monitor (MERCO ranking.
Evaluating the effectiveness of palm oil certification in delivering multiple sustainability objectives

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Morgans, Courtney L.; Meijaard, Erik; Santika, Truly; Law, Elizabeth; Budiharta, Sugeng; Ancrenaz, Marc; Wilson, Kerrie A.

2018-06-01

Industrial oil palm plantations in South East Asia have caused significant biodiversity losses and perverse social outcomes. To address concerns over plantation practices and in an attempt to improve sustainability through market mechanisms, civil society organisations and industry representatives developed the Roundtable on Sustainable Palm Oil (RSPO) in 2004. The effectiveness of RSPO in improving the sustainability of the palm oil industry is frequently debated and to date, few quantitative analyses have been undertaken to assess how successful RSPO has been in delivering the social, economic and environmental sustainability outcomes it aims to address. With the palm oil industry continuing to expand in South East Asia and significant estates being planted in Africa and South America, this paper evaluates the effectiveness of RSPO plantations compared to non-certified plantations by assessing the relative performance of several key sustainability metrics compared to business as usual practices. Using Indonesian Borneo (Kalimantan) as a case study, a novel dataset of RSPO concessions was developed and causal analysis methodologies employed to evaluate the environmental, social and economic sustainability of the industry. No significant difference was found between certified and non-certified plantations for any of the sustainability metrics investigated, however positive economic trends including greater fresh fruit bunch yields were revealed. To achieve intended outcomes, RSPO principles and criteria are in need of substantial improvement and rigorous enforcement.
Electroencephalographic Changes Associated with Antinociceptive Actions of Lidocaine, Ketamine, Meloxicam, and Morphine Administration in Minimally Anaesthetized Dogs

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Ubedullah Kaka

2015-01-01

Full Text Available Effects of ketamine and lidocaine on electroencephalographic (EEG changes were evaluated in minimally anaesthetized dogs, subjected to electric stimulus. Six dogs were subjected to six treatments in a crossover design with a washout period of one week. Dogs were subjected to intravenous boluses of lidocaine 2 mg/kg, ketamine 3 mg/kg, meloxicam 0.2 mg/kg, morphine 0.2 mg/kg and loading doses of lidocaine 2 mg/kg followed by continuous rate infusion (CRI of 50 and 100 mcg/kg/min, and ketamine 3 mg/kg followed by CRI of 10 and 50 mcg/kg/min. Electroencephalogram was recorded during electrical stimulation prior to any drug treatment (before treatment and during electrical stimulation following treatment with the drugs (after treatment under anaesthesia. Anaesthesia was induced with propofol and maintained with halothane at a stable concentration between 0.85 and 0.95%. Pretreatment median frequency was evidently increased (P<0.05 for all treatment groups. Lidocaine, ketamine, and morphine depressed the median frequency resulting from the posttreatment stimulation. The depression of median frequency suggested evident antinociceptive effects of these treatments in dogs. It is therefore concluded that lidocaine and ketamine can be used in the analgesic protocol for the postoperative pain management in dogs.
Antinociceptive action of DBO 17 and DBO 11 in mice: two 3,8 diazabicyclo (3.2.1.) octane derivates with selective mu opioid receptor affinity.

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Fadda, P; Barlocco, D; Tronci, S; Cignarella, G; Fratta, W

1997-11-01

Two 3,8 diazabicyclo (3.2.1.) octane derivates, namely DBO 17 and DBO 11, were studied for the opioid-like activity. In the rat brain membrane preparation binding studies, DBO 17 and DBO 11 showed a high affinity and selectivity for the mu opioid receptor (Ki's: 5.1 and 25 nM, respectively). DBO 17 and DBO 11 inhibited the nociceptive response in the hot-plate test of mice with ED50 values of 0.16 mg/kg and 0.44 mg/kg, respectively. The antinociceptive action of both DBO 17 and DBO 11 was blocked by naloxone. Tolerance to the antinociceptive action of DBO 17 and DBO 11 was present after 13 and 7 days of repeated treatment, respectively. Both DBO 17 and DBO 11 were ineffective in morphine-tolerant mice and vice versa. Chronic treatments (three times daily for seven consecutive days) of DBO 17 and DBO 11 induced a naloxone-precipitated withdrawal syndrome in DBO 17 treated mice similar to that in morphine treated mice, whereas in DBO 11 treated mice abstinence signs were virtually absent. These results indicate an interesting pharmacological profile that suggests these compounds as possible new candidates for the clinical treatment of pain.
Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

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Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

2007-12-01

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.
Effect of Corrupt Behavior of the Forestry Bureaucrats on the Forest Sustainability

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Sudarsono Soedomo

2012-11-01

Full Text Available 800x600 This article show that corrupt bureaucrats do not always result in a negative effect on the forest sustainability. Even under a certain condition, a corrupt behavior may result in a positive effect on the forest sustainability. An inappropriate policy is more important a cause of the forest sustainability than a corrupt behavior. Therefore, fixing this structural mistake needs to be prioritized in combating the forest destruction, for this structural mistake is the real primary cause of the forest destruction in Indonesia. Fixing this structural mistake is much more effective in combating the forest destruction than finding honest bureaucrats. Keywords: Birokrat, Distortionary, Nondistortionary, Kelestarian, Korup. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4

Sustainability of hydrogen supply chain. Part I: Identification of critical criteria and cause–effect analysis for enhancing the sustainability using DEMATEL

DEFF Research Database (Denmark)

Ren, Jingzheng; Manzardo, Alessandro; Toniolo, Sara

2013-01-01

The enhancement of sustainability of hydrogen supply chain is of vital importance for the stakeholders/decision-makers to design a sustainable hydrogen supply chain. The objective of this paper is to develop a method for prioritizing the influential factors, identifying the key driving factors...... that influence the sustainability of hydrogen supply chain and mapping the cause–effect relationships to improve the sustainability of hydrogen supply chain. In this paper, thirty seven criteria in four aspects including economic, technological, environmental and societal aspects are considered for enhancing...... the sustainability of hydrogen supply chain, and decision making trial and evaluation laboratory has been used to analyze the relationships among these criteria. The status of hydrogen supply chain in China has been studied by the proposed method, and the results are consistent with the actual conditions. It could...
Chewing and Attention: A Positive Effect on Sustained Attention

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Onozuka, Minoru

2015-01-01

Chewing is crushing food not only to aid swallowing and digestion, but also to help stress relief and regulate cognitive function, especially in attention. It is well known that chewing gum is used for sleepiness prevention during work, learning, and driving, suggesting a link between chewing and sustained attention. We hypothesized that chewing elevates attention and/or alertness, leading to improvements in cognitive performance. We carried out a systematic review of the PubMed database. We inspected the attributes of effects on attention in studies investigating the effects of chewing on attention or alertness conducted with pre-post design in healthy subjects, except elderly. We identified 151 references, 22 of which were included: 14 (64%) showed positive attributes of effects on attention, 1 (5%) showed negative attributes of effects on attention, 5 (23%) showed both positive and negative attributes of effects on attention, and 2 (9%) showed no significant attributes of effects on attention. Thus, positive attributes of effects of chewing on attention, especially on sustained attention, were shown in over half of the reports. These effects also appeared with improvement in mood and stress relief and were influenced by time-on-task effect. Further studies are needed, but chewing could be useful for modifying cognitive function. PMID:26075234
Chewing and Attention: A Positive Effect on Sustained Attention

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Yoshiyuki Hirano

2015-01-01

Full Text Available Chewing is crushing food not only to aid swallowing and digestion, but also to help stress relief and regulate cognitive function, especially in attention. It is well known that chewing gum is used for sleepiness prevention during work, learning, and driving, suggesting a link between chewing and sustained attention. We hypothesized that chewing elevates attention and/or alertness, leading to improvements in cognitive performance. We carried out a systematic review of the PubMed database. We inspected the attributes of effects on attention in studies investigating the effects of chewing on attention or alertness conducted with pre-post design in healthy subjects, except elderly. We identified 151 references, 22 of which were included: 14 (64% showed positive attributes of effects on attention, 1 (5% showed negative attributes of effects on attention, 5 (23% showed both positive and negative attributes of effects on attention, and 2 (9% showed no significant attributes of effects on attention. Thus, positive attributes of effects of chewing on attention, especially on sustained attention, were shown in over half of the reports. These effects also appeared with improvement in mood and stress relief and were influenced by time-on-task effect. Further studies are needed, but chewing could be useful for modifying cognitive function.
Chewing and attention: a positive effect on sustained attention.

Science.gov (United States)

Hirano, Yoshiyuki; Onozuka, Minoru

2015-01-01

Chewing is crushing food not only to aid swallowing and digestion, but also to help stress relief and regulate cognitive function, especially in attention. It is well known that chewing gum is used for sleepiness prevention during work, learning, and driving, suggesting a link between chewing and sustained attention. We hypothesized that chewing elevates attention and/or alertness, leading to improvements in cognitive performance. We carried out a systematic review of the PubMed database. We inspected the attributes of effects on attention in studies investigating the effects of chewing on attention or alertness conducted with pre-post design in healthy subjects, except elderly. We identified 151 references, 22 of which were included: 14 (64%) showed positive attributes of effects on attention, 1 (5%) showed negative attributes of effects on attention, 5 (23%) showed both positive and negative attributes of effects on attention, and 2 (9%) showed no significant attributes of effects on attention. Thus, positive attributes of effects of chewing on attention, especially on sustained attention, were shown in over half of the reports. These effects also appeared with improvement in mood and stress relief and were influenced by time-on-task effect. Further studies are needed, but chewing could be useful for modifying cognitive function.
Attribute Segmentation and Communication Effects on Healthy and Sustainable Consumer Diet Intentions

NARCIS (Netherlands)

Verain, Muriel; Sijtsema, Siet; Dagevos, Hans; Antonides, Gerrit

2017-01-01

A shift towards more sustainable consumer diets is urgently needed. Dietary guidelines state that changes towards less animal-based and more plant-based diets are beneficial in terms of sustainability and, in addition, will have a positive effect on public health. Communication on these guidelines
ERP characterization of sustained attention effects in visual lexical categorization.

Directory of Open Access Journals (Sweden)

Clara D Martin

Full Text Available As our understanding of the basic processes underlying reading is growing, the key role played by attention in this process becomes evident. Two research topics are of particular interest in this domain: (1 it is still undetermined whether sustained attention affects lexical decision tasks; (2 the influence of attention on early visual processing (i.e., before orthographic or lexico-semantic processing stages remains largely under-specified. Here we investigated early perceptual modulations by sustained attention using an ERP paradigm adapted from Thierry et al. [1]. Participants had to decide whether visual stimuli presented in pairs pertained to a pre-specified category (lexical categorization focus on word or pseudoword pairs. Depending on the lexical category of the first item of a pair, participants either needed to fully process the second item (hold condition or could release their attention and make a decision without full processing of the second item (release condition. The P1 peak was unaffected by sustained attention. The N1 was delayed and reduced after the second item of a pair when participants released their attention. Release of sustained attention also reduced a P3 wave elicited by the first item of a pair and abolished the P3 wave elicited by the second. Our results are consistent with differential effects of sustained attention on early processing stages and working memory. Sustained attention modulated early processing stages during a lexical decision task without inhibiting the process of stimulus integration. On the contrary, working memory involvement/updating was highly dependent upon the allocation of sustained attention. Moreover, the influence of sustained attention on both early and late cognitive processes was independent of lexical categorization focus.
Evaluation of the analgesic and anti-inflammatory effects of the essential oil of Lippia gracilis leaves.

Science.gov (United States)

Mendes, S S; Bomfim, R R; Jesus, H C R; Alves, P B; Blank, A F; Estevam, C S; Antoniolli, A R; Thomazzi, S M

2010-06-16

The aim of the present study is to investigate the antinociceptive, anti-inflammatory, and antioxidant activities of essential oil (EO) of Lippia gracilis Schauer (Verbenaceae) leaves to support the medicinal uses claimed by folklore practitioners in the caatinga region (semi-arid) of Northeastern Brazil. The chemical composition and antinociceptive and anti-inflammatory activities of the EO of Lippia gracilis leaves (50-200 mg/kg) were investigated. Antinociceptive activity of the EO was evaluated by writhing test. Anti-inflammatory activity of the EO was evaluated using paw oedema and peritonitis methods. Oral treatment with the EO of Lippia gracilis leaves elicited inhibitory activity on acetic acid effect at 50, 100, and 200 mg/kg (30.33+/-2.36, 25.20+/-1.48, and 21.00+/-1.54 abdominal writhes, respectively, Pleaves at 200 mg/kg (0.72+/-0.06 mL h, Pleaves at 50, 100, and 200 mg/kg (13.81+/-0.61, 11.77+/-0.91, and 10.30+/-0.60 leukocytes x 10(6)/mL, respectively, Pessential oil allowed the identification of Lippia gracilis as a thymol-p-cymene chemotype (32.68% and 17.82%, respectively). The EO of Lippia gracilis leaves shows antinociceptive and anti-inflammatory activities. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
The effect of opioid antagonists on synergism between dexketoprofen and tramadol.

Science.gov (United States)

Zegpi, C; Gonzalez, C; Pinardi, G; Miranda, H F

2009-10-01

The antinociceptive activity of dexketoprofen was studied in mice using the formalin assay for orofacial pain. The interaction between dexketoprofen and co-administered tramadol was studied using isobolographic analysis. The intraperitoneal administration of dexketoprofen or tramadol, showed dose-dependent antinociceptive activity in both phases of the assay. When administered together, the interaction was mildly synergistic during the first phase, and antagonistic in the second phase. Selective opioid receptor antagonists where used in order to measure the analgesic activity of tramadol in other regions of the CNS. The co-administration of dexketoprofen and tramadol, with previous administration of naltrexone, showed high synergistic activity during the first phase, and less but still synergistic during the second. When using naltrindole, the interaction was mildly more synergistic than the mixture dexketoprofen+tramadol during both phases. Using norbinaltorphimine, the interaction was synergistic in both phases, more marked in the second. These results suggest that the opioid activity of tramadol has an inhibiting effect in antinociceptive activity of the interaction between dexketoprofen and tramadol during the inflammatory (late) stages of pain.
Sustainability effects of household-scale biogas in rural China

International Nuclear Information System (INIS)

Gosens, Jorrit; Lu, Yonglong; He, Guizhen; Bluemling, Bettina; Beckers, Theo A.M.

2013-01-01

Households in rural China rely heavily on low quality fuels which results in reduced quality of life and environmental degradation. This study assesses the comparative contribution of household scale biogas installations to the broad set of sustainability objectives in the Chinese biogas policy framework, which targets household budget, fuel collection workload, forest degradation, indoor air quality and health, renewable energy supply, and climate change. A household survey was used to determine how biogas affected consumption levels of crop residues, fuel wood, coal, LPG, and electricity. Biogas users were found to reduce consumption of biomass fuels but not coal. Although LPG is not a highly commonly used fuel in rural China, biogas users nearly cease to use it altogether. A big reduction in fuel wood consumption results in strongly reduced workload and forest degradation. Although household scale biogas has alleviated all sustainability issues targeted by Chinese policies, low quality fuel use remains abundant, even in households using biogas. Continued promotion of the construction of biogas installations is advisable, but additional policies are needed to ensure higher quality heating energy supply and cleaner uses of biomass fuels. - Highlights: ► Household biogas alleviated all sustainability issues targeted by policy. ► Biogas users consume less biomass fuels, much less LPG, but similar amounts of coal. ► Strongest sustainability effects are reduced workload and forest degradation. ► Household budget effects are slight as commercial cooking fuel use is limited. ► Low quality fuel use remains abundant and further policy efforts are needed
What are the Most Effective Drivers of Sustainable Development in the Decision Making Process

DEFF Research Database (Denmark)

Hansen, Hanne Tine Ring; Knudstrup, Mary-Ann

2017-01-01

The identification of the most effective drivers of sustainable development is a focal point for most – if not all – policymakers and companies interested in sustainable development. Whilst the answer to this is of course very contextual this paper presents a practitioner’s review of the political...... and sustaining the market demand for sustainable buildings it is actually the economic and social drivers for sustainable building, such as life cycle costs, futureproofing of investments, better quality and Corporate Social Responsibility (CSR), that have the greatest impact on construction clients’ decision...
Antiinflammatory effects of Viola tricolor gel in a model of sunburn in rats and the gel stability study.

Science.gov (United States)

Piana, Mariana; Silva, Mariane Arnoldi; Trevisan, Gabriela; de Brum, Thiele Faccim; Silva, Cássia Regina; Boligon, Aline Augusti; Oliveira, Sara Marchesan; Zadra, Marina; Hoffmeister, Carin; Rossato, Mateus Fortes; Tonello, Raquel; Laporta, Luciane Varini; de Freitas, Robson Borba; Belke, Bianca Vargas; Jesus, Roberta da Silva; Ferreira, Juliano; Athayde, Margareth Linde

2013-11-25

Viola tricolor, popularly known as heartsease has been empirically used in several skin disorders, including burns. The objective of this study was investigate the antinociceptive and antiinflammatory effect of a gel containing extract of Viola tricolor flowers on thermal burn induced by UVB irradiation and to perform gel stability study. The antinociceptive and antiinflammatory effect were evaluated by static and dynamic mechanical allodynia model, paw edema, and neutrophilic cell infiltration. Metabolites compounds were quantified by HPLC. The gel stability study was performed analyzing organoleptical aspects, besides pH, viscosity, and quantification of rutin by HPLC. In the results were evidenced changes in threshold in statical and dynamic mechanical allodynia (I(max)=100 ± 10% and 49 ± 10%, respectively), paw edema (I(max)=61 ± 6%), and myeloperoxidase activity (I(max)=89 ± 5%). Such effects may be attributed, in part, to rutin, salicylic and chlorogenic acids, and others compounds found in this species. No important changes were detected in the stability study, in all aspects analyzed in temperature below 25 °C. These findings suggest that Viola tricolor gel has an antinociceptive and antiinflammatory effect in the ultraviolet-B-induced burn, since maintain the temperature below 25 °C. © 2013 Elsevier Ireland Ltd. All rights reserved.
Structural model to evaluate the effect of participation and satisfaction on ecotourism sustainability

Science.gov (United States)

Kencana, Eka N.; Manutami, T.

2017-10-01

This paper is directed to study the effect of local community participation and visitors’ satisfaction on ecotourism sustainability at Badung regency of Bali province, Indonesia. Two important aspects regarding ecotourism sustainability had been studied, i.e. (a) economic benefits for local people and (b) tourists’ satisfaction. Applying variance-based structural equation modeling, data were collected in July 2015 from local community leaders of Kiadan Village at Badung regency and tourists whom visited this village, were analysed. Four latent variables, namely (a) community participation, (b) economic benefits, (c) tourists’ satisfaction, and (d) ecotourism sustainability, were used to build structural model. The results showed sustainability of Kiadan’s ecotourism was significantly affected by local community participation and visitors’ satisfaction although community participation’s effect slightly greater than tourists’ satisfaction with path values for participation and satisfaction as much as 0.651 and 0.627, respectively.
Can the Clean Development Mechanism attain both cost-effectiveness and sustainable development objectives?

International Nuclear Information System (INIS)

Kolshus, Hans H; Vevatne, Jonas; Torvanger, Asbjoern; Aunan, Kristin

2001-06-01

The Clean Development Mechanism (CDM), as defined in the Kyoto Protocol, has two objectives: to promote sustainable development in host developing countries, and to improve global cost-effectiveness by assisting developed countries in meeting their Kyoto targets. The aim of this paper is to explore the background of the CDM and discuss to what extent its current design allows it to achieve its dual objective. The first part of the paper is a literature review that includes descriptions of the flexibility mechanisms under the Kyoto Protocol; the CDM's market potential, and the issues of cost-effectiveness and sustainable development. In the second part of the paper, we discuss to what extent there is a conflict between cost-effectiveness and sustain ability, and whether the two objectives of the CDM can be achieved simultaneously. We develop a set of indicators to evaluate non-carbon benefits of CDM projects on the environment, development, and. equity, and show how these indicators can be used in practice by looking at case studies of CDM project candidates in the energy sector from Brazil and China. We demonstrate that for some CDM projects there is a trade-off between cost-effectiveness, in terms of a low quota price, and a high score on sustain ability indicators. We have reason to believe that the size of the CDM market in some studies is over-estimated since transaction costs and the challenge of promoting sustainable development are not fully accounted for. Also, we find that the proposed set of indicators can be a necessary tool to assure that sustain ability impacts of CDM projects are taken into consideration. (author)
Can the Clean Development Mechanism attain both cost-effectiveness and sustainable development objectives?

Energy Technology Data Exchange (ETDEWEB)

Kolshus, Hans H; Vevatne, Jonas; Torvanger, Asbjoern; Aunan, Kristin

2001-06-01

The Clean Development Mechanism (CDM), as defined in the Kyoto Protocol, has two objectives: to promote sustainable development in host developing countries, and to improve global cost-effectiveness by assisting developed countries in meeting their Kyoto targets. The aim of this paper is to explore the background of the CDM and discuss to what extent its current design allows it to achieve its dual objective. The first part of the paper is a literature review that includes descriptions of the flexibility mechanisms under the Kyoto Protocol; the CDM's market potential, and the issues of cost-effectiveness and sustainable development. In the second part of the paper, we discuss to what extent there is a conflict between cost-effectiveness and sustain ability, and whether the two objectives of the CDM can be achieved simultaneously. We develop a set of indicators to evaluate non-carbon benefits of CDM projects on the environment, development, and. equity, and show how these indicators can be used in practice by looking at case studies of CDM project candidates in the energy sector from Brazil and China. We demonstrate that for some CDM projects there is a trade-off between cost-effectiveness, in terms of a low quota price, and a high score on sustain ability indicators. We have reason to believe that the size of the CDM market in some studies is over-estimated since transaction costs and the challenge of promoting sustainable development are not fully accounted for. Also, we find that the proposed set of indicators can be a necessary tool to assure that sustain ability impacts of CDM projects are taken into consideration. (author)
Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.

Science.gov (United States)

Athanasos, Peter; Ling, Walter; Bochner, Felix; White, Jason M; Somogyi, Andrew A

2018-03-05

Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Ambulatory. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range = 2-22 mg); no dose change for 1.5-12 months. Ten healthy controls. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Cold pressor responses (seconds): baseline: control 34 ± 6 vs buprenorphine 17 ± 2 (P = 0.009); morphine infusion-end: control 52 ± 11(P = 0.04), buprenorphine 17 ± 2 (P > 0.5); electrical stimulation responses (volts): baseline: control 65 ± 6 vs buprenorphine 53 ± 5 (P = 0.13); infusion-end: control 74 ± 5 (P = 0.007), buprenorphine 53 ± 5 (P > 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P = 0.03); infusion-end: control 15 (P = 0.09), buprenorphine 12 (P < 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 ± 1
Survey on Impact of Public push on Sustainability marketing mix and Sustainability marketing mix on Sustainability marketing success

OpenAIRE

iman mousavian; bahram kheiry; vahidreza mirabi

2014-01-01

Partaking the movement in reaching a more sustainable planet, organizations should reconsider their marketing strategies according to the social and environmental impacts. Even though, attaining sustainability would become a serious challenge for them, but there exist no other options for the third millennium. The main purpose of this study is to investigate the Impact of public push on the sustainability marketing mix, as well as the effect of sustainability marketing mix on sustainability m...
Starting the Pluralistic Tradition of Teaching? Effects of Education for Sustainable Development (ESD) on Pre-Service Teachers' Views on Teaching about Sustainable Development

Science.gov (United States)

Andersson, Klas

2017-01-01

There is currently a well-established belief among politicians, scholars and university representatives that educational systems can produce positive attitudes towards sustainable development (SD) among citizens. This article investigates whether Education for Sustainable Development (ESD) in teacher education has effects on pre-service teachers'…
The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

Science.gov (United States)

Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

2017-10-01

Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.
Effects of Hydroalcoholic Extract of Tanacetum Sonbolii (Asteraceae on Pain-related Behaviors during Formalin Test in Mice

Directory of Open Access Journals (Sweden)

Mohammad Sofiabadi

2014-05-01

Full Text Available Introduction: Tanacetum sonbolii (Asteraceae is an endemic species in Iran. In the present study, we examined the effects of Tanacetum sonbolii hydroalcoholic extract on the formalin test in mice. Methods: 126 Swiss albino mice weighing 230-280g were used as subjects. The formalin test was performed on two control groups (marked as intact and saline groups n = 6 in each group and an experimental group. In all groups, the formalin test was recorded for 60 min after administration of extract and drugs in mice. Results: The results showed that Tanacetum sonbolii (150 and 300 mg/kg produced significant antinociception in phase 2. In addition, different doses of Tanacetum sonbolii extract (600, 900 and 1200 mg/kg also induced antinociceptive effects in phase1 and phase 2. On the other hand, morphine could induce antinociception in a dose-dependent manner. Diclofenac (10 mg/kg failed to affect the pain scores compared to Tanacetum sonbolii (300 mg/kg group. Discussion: It seems that administration of hydroalcoholic extract of Tanacetum sonbolii has the potential to relieve pain through both central and peripheral mechanisms in persistent inflammatory nociception.
Antinociceptive effects of clebopride in the mouse.

Science.gov (United States)

Bittencourt, S C; De Lima, T C; Morato, G S

1995-09-01

1. The effects of the substituted benzamide clebopride, an orthopramide, on nociception of chemical and thermal stimuli were investigated. 2. Clebopride (0.5, 1.0 and 2.0 mg/kg) promoted significant analgesia in the tail-flick and hot-plate tests and against abdominal constrictions produced by acetic acid or acetylcholine. 3. The analgesic effects of clebopride were not influenced by pretreatment with naltrexone (1-3 mg/kg). 4. The results suggest that clebopride induces analgesia against both thermal and chemical nociceptive stimuli, which is not mediated via opioid mechanisms.

Sustainable packaging: from eco-efficiency to eco-effectiveness

DEFF Research Database (Denmark)

Niero, Monia; Boas, Simon H.; Olsen, Stig Irving

2014-01-01

According to Verghese et al (2012) sustainable packaging should be: effective in delivering its functional requirements, efficient in its use of materials, energy, and water throughout its life cycle, cyclic in its use of renewable materials and recoverability at end-of-life, and safe for people...... and the natural environment. Companies in the packaging sector have traditionally been using the Life Cycle Assessment (LCA) methodology to fulfill these requirements. However, being inspired by the eco-efficiency principle, LCA aims to reduce the negative environmental footprint of human activities by optimizing...... and emissions can be taken up as nutrients by other processes instead of reducing the amount of waste as eco-efficiency advocates. From a company point of view, LCA and C2C are complementary approaches to develop sustainable andinnovative solutions for packaging, see Figure 1. We will illustrate the challenges...
Effective Disclosure in the Fast-Fashion Industry: from Sustainability Reporting to Action

Directory of Open Access Journals (Sweden)

Sofia Garcia-Torres

2017-12-01

Full Text Available This work, set in the context of the apparel industry, proposes an action-oriented disclosure tool to help solve the sustainability challenges of complex fast-fashion supply chains (SCs. In a search for effective disclosure, it focusses on actions towards sustainability instead of the measurements and indicators of its impacts. We applied qualitative and quantitative content analysis to the sustainability reporting of the world’s two largest fast-fashion companies in three phases. First, we searched for the challenges that the organisations report they are currently facing. Second, we introduced the United Nations’ Sustainable Development Goals (SDGs framework to overcome the voluntary reporting drawback of ‘choosing what to disclose’, and revealed orphan issues. This broadened the scope from internal corporate challenges to issues impacting the ecosystems in which companies operate. Third, we analysed the reported sustainability actions and decomposed them into topics, instruments, and actors. The results showed that fast-fashion reporting has a broadly developed analysis base, but lacks action orientation. This has led us to propose the ‘Fast-Fashion Sustainability Scorecard’ as a universal disclosure framework that shifts the focus from (i reporting towards action; (ii financial performance towards sustainable value creation; and (iii corporate boundaries towards value creation for the broader SC ecosystem.
Role of Magnesium Sulfate in Prolonging the Analgesic Effect of ...

African Journals Online (AJOL)

antinociceptive effect in animal and human pain models. i.v magnesium ... about 30 min prior to surgery followed by continuous infusion at the rate of 10 mg/kg/h for the next 24 h while the other group received similar ... of analgesia and reduces postoperative analgesic consumption without any significant side effects.
Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome.

Science.gov (United States)

Ullah, H M Arif; Zaman, Sayera; Juhara, Fatematuj; Akter, Lucky; Tareq, Syed Mohammed; Masum, Emranul Haque; Bhattacharjee, Rajib

2014-09-22

The present study was aimed to investigate the antinociceptive and anti-inflammatory activity of the Curcuma zedoaria (family Zingiberaceae) ethanolic rhizome extract in laboratory using both in vitro and in vivo methods so as to justify its traditional use in the above mentioned pathological conditions. Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo antinociceptive activity was performed employing the hot plate method, acidic acid induced writhing test and formalin induced writhing test on Swiss albino mice at doses of 250 and 500 mg/kg body weight. Anti-inflammatory activity test was done on Long Evans rats at two different doses (250 and 500 mg/kg body weight) by using carrageenan induced paw edema test. Finally in vitro anti-inflammatory test by protein-denaturation method was followed. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett's t-test was used as the test of significance. P value <0.05 was considered as the minimum level of significance. Phytochemical screening revealed presence of tannins, saponins, flavonoids, gums & carbohydrates, steroids, alkaloids, reducing sugars and terpenoids in the extract. In the hot plate method, the extract increased the reaction time of heat sensation significantly to 61.99% and 78.22% at the doses of 250 and 500 mg/kg BW respectively. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 48.28% and 54.02% at 250 and 500 mg/kg doses respectively (p < 0.001). The extract also significantly inhibited the licking response in both the early phase (64.49%, p < 0.01) and the late phase (62.37%, p < 0.01) in formalin induced writhing test. The extract significantly (p < 0.05, p < 0.01 and p < 0.001) inhibited carrageenan induced inflammatory response in rats in a dose related manner. In in-vitro anti-inflammatory test, the extract significantly inhibited protein denaturation of 77.15, 64.43, 53
Effective integrated frameworks for assessing mining sustainability.

Science.gov (United States)

Virgone, K M; Ramirez-Andreotta, M; Mainhagu, J; Brusseau, M L

2018-05-28

The objectives of this research are to review existing methods used for assessing mining sustainability, analyze the limited prior research that has evaluated the methods, and identify key characteristics that would constitute an enhanced sustainability framework that would serve to improve sustainability reporting in the mining industry. Five of the most relevant frameworks were selected for comparison in this analysis, and the results show that there are many commonalities among the five, as well as some disparities. In addition, relevant components are missing from all five. An enhanced evaluation system and framework were created to provide a more holistic, comprehensive method for sustainability assessment and reporting. The proposed framework has five components that build from and encompass the twelve evaluation characteristics used in the analysis. The components include Foundation, Focus, Breadth, Quality Assurance, and Relevance. The enhanced framework promotes a comprehensive, location-specific reporting approach with a concise set of well-defined indicators. Built into the framework is quality assurance, as well as a defined method to use information from sustainability reports to inform decisions. The framework incorporates human health and socioeconomic aspects via initiatives such as community-engaged research, economic valuations, and community-initiated environmental monitoring.
In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Directory of Open Access Journals (Sweden)

D.O. Gonçalves

2011-02-01

Full Text Available Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g, which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan, at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively. Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively and second phase (73, 57, and 66% inhibition of licking time, respectively. The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc. Lovastatin (0.01, 0.1, and 1 µg/mL inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α and the inducible form of nitric oxide synthase (iNOS activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.
Levee Setbacks: An Innovative, Cost Effective, and Sustainable Solution for Improved Flood Risk management

Science.gov (United States)

2017-06-30

ER D C/ EL S R- 17 -3 Levee Setbacks: An Innovative , Cost-Effective, and Sustainable Solution for Improved Flood Risk Management En vi...EL SR-17-3 June 2017 Levee Setbacks: An Innovative , Cost-Effective, and Sustainable Solution for Improved Flood Risk Management David L. Smith...alternative view point is necessary. ERDC/EL SR-17-3 4 Levee setbacks are a relatively recent innovation in Corps flood risk management practice
Glucose and caffeine effects on sustained attention: an exploratory fMRI study.

Science.gov (United States)

Serra-Grabulosa, Josep M; Adan, Ana; Falcón, Carles; Bargalló, Núria

2010-11-01

Caffeine and glucose can have beneficial effects on cognitive performance. However, neural basis of these effects remain unknown. Our objective was to evaluate the effects of caffeine and glucose on sustained attention, using functional magnetic resonance imaging (fMRI). Forty young right-handed, healthy, low caffeine-consuming subjects participated in the study. In a double-blind, randomised design, subjects received one of the following beverages: vehicle (water, 150 ml); vehicle plus 75 g of glucose; vehicle plus 75 mg of caffeine; vehicle plus 75 g of glucose and 75 mg of caffeine. Participants underwent two scanning fMRI sessions (before and 30 min after of the administration of the beverage). A continuous performance test was used to assess sustained attention. Participants who received combined caffeine and glucose had similar performance to the others but had a decrease in activation in the bilateral parietal and left prefrontal cortex. Since these areas have been related to the sustained attention and working memory processes, results would suggest that combined caffeine and glucose could increase the efficiency of the attentional system. However, more studies using larger samples and different levels of caffeine and glucose are necessary to better understand the combined effects of both substances. Copyright © 2010 John Wiley & Sons, Ltd.
Undergraduate Sustainable Learning: Effects of Sustainable Soilless Media on Production and Sensory Evaluation of Cucumbers, Basil, Parsley, and Lettuce

Directory of Open Access Journals (Sweden)

Victoria Russell

2011-08-01

Full Text Available Modern greenhouse production has been ~100% reliant on fossil fuels for all inputs (glazing, heating, fertilization, lighting, post-harvest. Recent innovations may reduce fossil fuel dependence but their effectiveness may not be thoroughly tested. To promote education in sustainable production, undergraduate students in Greenhouse Management class (Hort 3002W; University of Minnesota tested the effectiveness of two organic or ‘sustainable’ soilless media (Sunshine Natural and Organic Growing Mix, Sungro Metro-Mix Special Blend with a control (Sunshine LC8 Professional for crop production (height, leaf/flower number, yield and sensory evaluations (appearance, texture, taste, purchase of cucumbers (‘Big Burpless Hybrid’, ‘Sweet Burpless Hybrid’, basil (‘Opal Purple’, ‘Redleaf’, parsley (‘Green River’, ‘Extra Curled Dwarf’, ‘Hamburg’, and lettuce (Flying Saucer ‘Green’, ‘Red’. Significant differences between sustainable vs. control soils occurred for plant growth, depending on vegetative or reproductive traits, crops, and cultivars. These differences occasionally disappeared for sensory evaluation of edible components. In most crops, however, cultivars were highly significant factors. Undergraduate research can be used to provide directionality for future vegetable and herb plant breeding to focus on creating cultivars with increased yield and high consumer acceptance when grown in sustainable greenhouse soilless mixes.
Involvement of nitric oxide and ATP-sensitive potassium channels in the peripheral antinoceptive action of a tramadol-dexketoprofen combination in the formalin test.

Science.gov (United States)

Isiordia-Espinoza, Mario A; Pozos-Guillén, Amaury; Pérez-Urizar, José; Chavarría-Bolaños, Daniel

2014-11-01

Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)-cyclic guanosine monophosphate pathway and ATP-sensitive K(+) channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction during the second phase of the formalin test. Pretreatment with NO antagonists, including l-NG-nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K(+) channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol-dexketoprofen combination, suggesting that NO and ATP-sensitive K(+) channels were involved. © 2014 Wiley Periodicals, Inc.
Development through sustainable tourism and effective policy implementation: Practices of Puerto Princesa City, Philippines

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Jazztin Jairum P. Manalo

2017-02-01

Full Text Available Sustainable tourism has been considered by many local governments as part of their initiatives for economic upliftment. It is one of the major sources of income through the use of their tourist attraction without compromising the natural resources situated within. The enactment and effective implementation of the local government’s policy have achieved a promising efficient outcome for sustainable tourism.. The city of Puerto Princesa had a long history considering its transformation from an environmentally degraded city into one of the major ecotourism sites around the world. Thus, this paper presents the case of Puerto Princesa and its practices as well as economic development by practicing sustainable tourism and effective policy implementation. The City Ordinance No. 163-91 and 640 has improved the lives of the communities by practicing cleanliness and effective waste management their surrounding and tourist destinations. Economic development and benefits from sustainable tourism reflects the city of Puerto Princesa as a role model for Local Government Units. The passing of City Ordinances on Cleanliness drive have played an important role in effective waste management of the city. The key role of having a strong political will in the local government has strongly maintained its best practices for two decades up to the present.
Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity.

Science.gov (United States)

Wixted, Fiona; O'Riordan, Cliona; O'Sullivan, Leonard

2018-01-11

The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators' job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs). The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO₂ were evaluated. The breathing intervention reduced the moderation effect of end-tidal CO₂ on upper trapezius muscle activity. Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.
Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats

Energy Technology Data Exchange (ETDEWEB)

Abbott, F.V.; Palmour, R.M.

1988-01-01

The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced and increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catelepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of (/sup 3/H)-etorphine, (/sup 3/H)-dihydromorphine and (/sup 3/H)-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with K/sub i/ values of about 30 nM, as compared to morphine K/sub i/ values of about 3 nM.
Sustainability and Organizational Change by Sustainable Crediting Therapy

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Dragoş Ilie

2012-06-01

Full Text Available The objective of this paper is to demonstrate that one of the therapies to achieve sustainability and organizational change in the context of current challenges in the national economies is sustainable crediting. The research method is based on a survey of 30 commercial companies from various fields of activity that have or have not implemented, at the leadership level, the concept of sustainable crediting. The data collecting and processing approach has resulted in the determination of the main economic-financial indicators for a period of 5 years, indicators used by banks in relation with the credited organizations. The main results show that companies that have implemented the sustainable crediting concept are more able to achieve sustainability in their developed activity, as well as organizational change with positive effects on their business and on the company as a whole. The concept of sustainable crediting implies the capitalization of the commercial companies, the increase of the loan portfolio quality, the achievement of the financial balance and environmental protection
Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

Science.gov (United States)

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. PMID:27746208
Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

Science.gov (United States)

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.
Sustainability of University Technology Transfer: Mediating Effect of Inventor’s Technology Service

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Fang Li

2018-06-01

Full Text Available Based on the perspective of knowledge transfer and the technology acceptance model (TAM, this paper constructs a university technology transfer sustainable development model that considers the inventor’s technology service from the perspective of the long-term cooperation of enterprise, and analyzes the mediating effect of the inventor’s technology service on university technology transfer sustainability. By using 270 questionnaires as survey data, it is found that the availability of an inventor’s technology service has a significant positive impact on the attitude tendency and practice tendency of enterprise long-term technological cooperation; enterprise technology absorption capacity and trust between a university and an enterprise also have significant influence on an inventor’s technical service availability. Therefore, the inventor’s technology service acts as a mediator in the relationship between university technology transfer sustainability and influence factors. Universities ought to establish the technology transfer model, which focuses on the inventor’s tacit knowledge transfer service, and promotes the sustainable development of the university.
Anti-inflammatory, antinociceptive activity of an essential oil recipe consisting of the supercritical fluid CO2 extract of white pepper, long pepper, cinnamon, saffron and myrrh in vivo.

Science.gov (United States)

Zhang, Yuanbin; Wang, Xinfang; Ma, Ling; Dong, Lin; Zhang, Xinhui; Chen, Jing; Fu, Xueyan

2014-01-01

This study was designed to investigate the anti-inflammatory and antinociceptive activities of essential oil recipe (OR) in rodents. The anti-inflammatory activity was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice whereas the antinociceptive activity was evaluated using acetic acid-induced writhes and hot plate test methods in mice. Additionally, the chemical composition of OR has been also analyzed by gas chromatography and mass spectrometry (GC/MS). 37 compounds, representing 74.42% of the total oil content, were identified. β-Selinene (7.38%), aromadendrene (5.30%), β-elemene (5.22%), cis-piperitol (5.21%), cis-β-guaiene (4.67%), ylangene (3.70%), 3-heptadecene (3.55%), δ-cadinene (3%) and β-cadinene (2.87%) were found to be the major constituents of the oil. Oral pretreatment with OR (62.5-1000 mg/kg) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. OR significantly reduced the writhing number evoked by acetic acid injection. All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. These data demonstrated that the OR inhibits inflammatory and peripheral inflammatory pain. These results may support the fact that the essential oil of traditional Hui prescription played a role in the inflammation of stroke.
Externality or sustainability economics?

International Nuclear Information System (INIS)

Bergh, Jeroen C.J.M. van den

2010-01-01

In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)
International cooperation to improve access to and sustain effectiveness of antimicrobials.

Science.gov (United States)

Årdal, Christine; Outterson, Kevin; Hoffman, Steven J; Ghafur, Abdul; Sharland, Mike; Ranganathan, Nisha; Smith, Richard; Zorzet, Anna; Cohn, Jennifer; Pittet, Didier; Daulaire, Nils; Morel, Chantal; Rizvi, Zain; Balasegaram, Manica; Dar, Osman A; Heymann, David L; Holmes, Alison H; Moore, Luke S P; Laxminarayan, Ramanan; Mendelson, Marc; Røttingen, John-Arne

2016-01-16

Securing access to effective antimicrobials is one of the greatest challenges today. Until now, efforts to address this issue have been isolated and uncoordinated, with little focus on sustainable and international solutions. Global collective action is necessary to improve access to life-saving antimicrobials, conserving them, and ensuring continued innovation. Access, conservation, and innovation are beneficial when achieved independently, but much more effective and sustainable if implemented in concert within and across countries. WHO alone will not be able to drive these actions. It will require a multisector response (including the health, agriculture, and veterinary sectors), global coordination, and financing mechanisms with sufficient mandates, authority, resources, and power. Fortunately, securing access to effective antimicrobials has finally gained a place on the global political agenda, and we call on policy makers to develop, endorse, and finance new global institutional arrangements that can ensure robust implementation and bold collective action. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of hydroethanolic extract of Ipomoea pes-caprae using factorial design followed by antinociceptive and anti-inflammatory evaluation

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Daniela Vieira

2012-11-01

Full Text Available Ipomoea pes-caprae (L. R. Br., Convolvulaceae, is a medicinal plant that grows abundantly as a pan-tropical stand plant. The 3² (two factors and three levels factorial design, was applied to determine the best time and drug/solvent proportion to maximize the flavonoid content in the hydroethanolic extract by maceration process. The antinociceptive and anti-inflammatory effects were studied at 5-20 mg/kg, i.p., using the writhing test and carrageenan-induced pleurisy models in mice. The optimized extract was able to inhibit more than 50% of abdominal writhing at 20 mg/kg, with 55.88%±2.4 of maximum inhibition. Indomethacin, used as positive control, inhibited 64.86% at 10 mg/kg. In the pleurisy model, the extract produced dose-dependent inhibition of the first phase of inflammation (4 h in the pleural cavity induced by injection of carrageenan (1% in mice. It inhibited 50%±0.82 (p<0.01 of exudation induced by carrageenan, and 60.88%±0.14 (p<0.01 of leukocyte migration to the pleural cavity. In conclusion, the results validate the technological conditions of the maceration process to produce an optimized bioactive herb extract for the development of analgesic and anti-inflammatory phytopharmaceuticals using 70 ºGL ethanol, a plant to solvent ratio of 12.5% (w/v, and ten days of maceration.
The Impact of Organisational Alignment on the Effectiveness of Firms' Sustainability Strategic Performance Measurement Systems

DEFF Research Database (Denmark)

Parisi, Cristiana

2013-01-01

concerns. This paper contributes to the research on integrating sustainability into companies’ daily activities both directly and indirectly. It analyses the extent to which top management’s commitment to sustainability directly affects structural and social alignment and the effectiveness of measurement...
The Avahan Transition: Effects of Transition Readiness on Program Institutionalization and Sustained Outcomes.

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Sachiko Ozawa

Full Text Available With declines in development assistance for health and growing interest in country ownership, donors are increasingly faced with the task of transitioning health programs to local actors towards a path to sustainability. Yet there is little available guidance on how to measure and evaluate the success of a transition and its subsequent effects. This study assesses the transition of the Avahan HIV/AIDS prevention program in India to investigate how preparations for transition affected continuation of program activities post-transition.Two rounds of two surveys were conducted and supplemented by data from government and Avahan Computerized Management Information Systems (CMIS. Exploratory factor analysis was used to develop two measures: 1 transition readiness pre-transition, and 2 institutionalization (i.e. integration of initial program systems into organizational procedures and behaviors post-transition. A fixed effects model was built to examine changes in key program delivery outcomes over time. An ordinary least square regression was used to assess the relationship between transition readiness and sustainability of service outcomes both directly, and indirectly through institutionalization.Transition readiness data revealed 3 factors (capacity, alignment and communication, on a 15-item scale with adequate internal consistency (alpha 0.73. Institutionalization was modeled as a unidimensional construct, and a 12-item scale demonstrated moderate internal consistency (alpha 0.60. Coverage of key populations and condom distribution were sustained compared to pre-transition levels (p<0.01. Transition readiness, but not institutionalization, predicted sustained outcomes post-transition. Transition readiness did not necessarily lead to institutionalization of key program elements one year after transition.Greater preparedness prior to transition is important to achieve better service delivery outcomes post-transition. This paper illustrates a
Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity

Directory of Open Access Journals (Sweden)

Fiona Wixted

2018-01-01

Full Text Available Objective: The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. Background: The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators’ job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs. Methods: The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO2 were evaluated. Results: The breathing intervention reduced the moderation effect of end-tidal CO2 on upper trapezius muscle activity. Conclusions: Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. Application: This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.
Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro-acupuncture in the formalin-induced inflammatory pain model of rats

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Xing Guo-Gang

2011-08-01

Full Text Available Abstract Acupuncture and electro-acupuncture (EA are now widely used to treat disorders like pain. We and others have shown previously that current frequency, intensity and treatment duration all significantly influence the anti-nociceptive effects of EA. There is evidence that stimulating sites also affect the antinociception, with EA applied ipsilaterally to the pain site being more effective under some pain states but contralateral EA under others. It was recently reported that local adenosine A1 receptors were responsible for ipsilateral acupuncture, but what mechanisms specifically mediate the anti-nociceptive effects of contralateral acupuncture or EA remains unclear. In the present study, we applied 100 Hz EA on the ipsi- or contra-lateral side of rats with inflammatory pain induced by intra-plantar injection of formalin, and reported distinct anti-nociceptive effects and mechanisms between them. Both ipsi- and contra-lateral EA reduced the paw lifting time in the second phase of the formalin test and attenuated formalin-induced conditioned place aversion. Contralateral EA had an additional effect of reducing paw licking time, suggesting a supraspinal mechanism. Lesions of rostral anterior cingulate cortex (ACC completely abolished the anti-nociceptive effects of contra- but not ipsi-lateral EA. These findings were not lateralized effects, since injection of formalin into the left or right hind paws produced similar results. Overall, these results demonstrated distinct anti-nociceptive effects and mechanisms between different stimulating sides and implied the necessity of finding the best stimulating protocols for different pain states.
Nicotine anxiogenic and rewarding effects are decreased in mice lacking beta-endorphin.

Science.gov (United States)

Trigo, José M; Zimmer, Andreas; Maldonado, Rafael

2009-06-01

The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, micro-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking beta-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking beta-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of beta-endorphin in these addictive related responses.
Nicotine anxiogenic and rewarding effects are decreased in mice lacking β-endorphin

Science.gov (United States)

Trigo, José M.; Zimmer, Andreas; Maldonado, Rafael

2009-01-01

The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, μ-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking β-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking β-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of β-endorphin in these addictive related responses. PMID:19376143
Short Intervention, Sustained Effects: Promoting Students’ Math Competence Beliefs, Effort, and Achievement

NARCIS (Netherlands)

Brisson, Brigitte Maria; Dicke, Anna Lena; Gaspard, Hanna; Häfner, Isabelle; Flunger, Barbara|info:eu-repo/dai/nl/412516322; Nagengast, Benjamin; Trautwein, Ulrich

2017-01-01

The present study investigated the effectiveness of two short relevance interventions (writing a text or evaluating quotations about the utility of mathematics) using a sample of 1,916 students in 82 math classrooms in a cluster randomized controlled experiment. Short-term and sustained effects (6
Effect of Economic Vulnerability on Competitive Advantages, Enterprise Performance and Sustainability

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Abdullah Al Mamun

2018-04-01

Full Text Available This study investigated the effect of economic vulnerability upon competitive advantages, performance, and sustainability of micro-enterprises owned and managed by micro-entrepreneurs who participate in varied development initiatives in Peninsular Malaysia. Upon adopting the cross-sectional design, data were randomly collected from selected 300 micro-entrepreneurs from the eKasih program (national poverty data bank located in four states of Peninsular Malaysia. The quantitative data were collected by conducting structured interview sessions with the respondents held from September until November 2017. The findings revealed that the state of economic vulnerability among the respondents had a significantly negative effect on the aspects of competitive advantages, performance, and sustainability among micro-enterprises in Peninsular Malaysia. Despite of the widely acknowledged and empirically examined effects of socioeconomic antecedents upon micro-enterprise performance, the focus on the effect of a more comprehensive measure of socioeconomic condition, that is, economic vulnerability, among low-income households appears to be scant. Hence, the outcomes of this study are able to provide critical insights for development organizations pertaining to development programs and their effectiveness on economically vulnerable, particularly among low-income households in Peninsular Malaysia.
A Dynamic Model of Sustainment Investment

Science.gov (United States)

2015-02-01

Sustainment System Dynamics Model 11 Figure 7: Core Structure of Sustainment Work 12 Figure 8: Bandwagon Effect Loop 13 Figure 9: Limits to Growth Loop 14...Dynamics Model sustainment capacity sustainment performance gap Bandwagon Effect R1 Limits to Growth B1 S Work Smarter B3 Work Bigger B2 desired...which is of concern primarily when using the model as a vehicle for research. Figure 8 depicts a reinforcing loop called the “ Bandwagon Effect
Three necessary conditions for establishing effective Sustainable Development Goals in the Anthropocene

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Albert V. Norström

2014-09-01

Full Text Available The purpose of the United Nations-guided process to establish Sustainable Development Goals is to galvanize governments and civil society to rise to the interlinked environmental, societal, and economic challenges we face in the Anthropocene. We argue that the process of setting Sustainable Development Goals should take three key aspects into consideration. First, it should embrace an integrated social-ecological system perspective and acknowledge the key dynamics that such systems entail, including the role of ecosystems in sustaining human wellbeing, multiple cross-scale interactions, and uncertain thresholds. Second, the process needs to address trade-offs between the ambition of goals and the feasibility in reaching them, recognizing biophysical, social, and political constraints. Third, the goal-setting exercise and the management of goal implementation need to be guided by existing knowledge about the principles, dynamics, and constraints of social change processes at all scales, from the individual to the global. Combining these three aspects will increase the chances of establishing and achieving effective Sustainable Development Goals.
Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

Science.gov (United States)

Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

2018-04-13

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.
Effectiveness of plant based insecticides as a sustainable means of ...

African Journals Online (AJOL)

Cucumber (Cucumis sativus) is an important crop in Pakistan. It is affected by many biotic and abiotic factors. Among these, Cucumber mosaic virus is the important disease with economic losses. The purpose of this study was to evaluate the effectiveness of plant based insecticides as a sustainable means to control the ...
Overall Bike Effectiveness as a Sustainability Metric for Bike Sharing Systems

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Bernardo Nugroho Yahya

2017-11-01

Full Text Available Bike sharing systems (BSS have been widely accepted as an urban transport scheme in many cities around the world. The concept is recently expanded and followed by many cities to offer citizen a “green” and flexible transportation scheme in urban areas. Many works focus on the issues of bike availability while the bike performance, i.e., life cycle issues and its sustainability, for better management has been abandoned. As a consequence, mismanagement of BSS would lead to cost inefficiency and, the worst case, end with operation termination. This study proposes a design science approach by developing an Overall Bike Effectiveness (OBE framework. By incorporating the concept of overall equipment analysis (OEE, the proposed framework is used to measure the bike utilization. Accordingly, the OBE is extended into Theoretical OBE to measure the sustainability of the early-stage of BSS. The framework has been verified and evaluated using a real dataset of BSS. The proposed method provides valuable results for benchmarking, life cycle analysis, system expansion and strategy planning toward sustainability. The paper concludes with a discussion to show the impact of the proposed approach into the real practices of BSS including an outlook toward sustainability of BSS.
Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

Energy Technology Data Exchange (ETDEWEB)

Adams, M.L.; Morris, D.L.; Dewey, W.L.

1986-03-05

..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.
Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

International Nuclear Information System (INIS)

Adams, M.L.; Morris, D.L.; Dewey, W.L.

1986-01-01

β-endorphin, [met]enkephalin, and [leu]enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO 4 or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. β-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; [met]enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; [leu]-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs
Conceptualising sustainability assessment

International Nuclear Information System (INIS)

Pope, Jenny; Annandale, David; Morrison-Saunders, Angus

2004-01-01

Sustainability assessment is being increasingly viewed as an important tool to aid in the shift towards sustainability. However, this is a new and evolving concept and there remain very few examples of effective sustainability assessment processes implemented anywhere in the world. Sustainability assessment is often described as a process by which the implications of an initiative on sustainability are evaluated, where the initiative can be a proposed or existing policy, plan, programme, project, piece of legislation, or a current practice or activity. However, this generic definition covers a broad range of different processes, many of which have been described in the literature as 'sustainability assessment'. This article seeks to provide some clarification by reflecting on the different approaches described in the literature as being forms of sustainability assessment, and evaluating them in terms of their potential contributions to sustainability. Many of these are actually examples of 'integrated assessment', derived from environmental impact assessment (EIA) and strategic environmental assessment (SEA), but which have been extended to incorporate social and economic considerations as well as environmental ones, reflecting a 'triple bottom line' (TBL) approach to sustainability. These integrated assessment processes typically either seek to minimise 'unsustainability', or to achieve TBL objectives. Both aims may, or may not, result in sustainable practice. We present an alternative conception of sustainability assessment, with the more ambitious aim of seeking to determine whether or not an initiative is actually sustainable. We term such processes 'assessment for sustainability'. 'Assessment for sustainability' firstly requires that the concept of sustainability be well-defined. The article compares TBL approaches and principles-based approaches to developing such sustainability criteria, concluding that the latter are more appropriate, since they avoid many
Effects of sustainable employability policies on organizational performance

NARCIS (Netherlands)

Kraan, K.O.; Sanders, J.

2015-01-01

Presentations on the 11th International Conference on Occupational Stress and Health. Session: organizational justice and sustainability: approaches and implications for performance and the bottom line. Interactive paper session: sustainability, occupational safety and health: developing a research
Sustainability Marketing Commitment

DEFF Research Database (Denmark)

Tollin, Karin; Bech Christensen, Lars

2017-01-01

sustainability in marketing, processes associated with sustainability marketing commitment, drivers of sustainability marketing at the functional level of marketing, and its organizational context. Using survey data from 269 managers in marketing, covering a broad range of industries in Sweden and Denmark, we...... took a structural modelling approach to examine construct relationships, mediation, and moderation effects. Overall, the findings show that marketing capabilities associated with the innovation of new products, services, and business models constitute a strong driver to leverage sustainability......Corporate sustainability is an important strategy and value orientation for marketing, but scarce research addresses the organizational drivers and barriers to including it in companies’ marketing strategies and processes. The purpose of this study is to determine levels of commitment to corporate...
The Effect of Board Independence on the Sustainability Reporting Practices of Large U.S. Firms \\

Directory of Open Access Journals (Sweden)

David N. Herda

2012-12-01

firms with a greater proportion of independent board members are: 1 more likely to publish standalone sustainability reports, and 2 more likely to publish higher quality sustainability reports. This paper contributes to prior literature that reports somewhat mixed results on the effect of board independence on voluntary disclosure.

The role of international sustainable development law principles in enabling effective renewable energy policy – a South African perspective.

Directory of Open Access Journals (Sweden)

Michelle Barnard

2012-08-01

Full Text Available It is universally accepted that renewable energy is an important contributing factor towards the promotion of sustainable development. The implementation of renewable energy needs to be regulated in an effective manner which in turn necessitates the formulation of law and policy geared towards sustainable development. Recent policy developments in South Africa propose to facilitate the promotion of sustainable development through the implementation of renewable energy, among others. In terms of existing energy policy in South-Africa, the interconnectivity of renewable energy and sustainable development is evident. Most notably, the White Paper on Renewable Energy of 2003 promotes increased access to affordable renewable energy in order to contribute to sustainable development. Moreover, the 2008 first review of the National Energy Efficiency Strategy of the Republic of South-Africa of 2005 states that in order for the country’s renewable energy policy to be considered sustainable, it needs to facilitate development in the social, economic and environmental spheres. Notwithstanding, attaining the goal of sustainable development depends on whether all its effecting principles are catered for in the policy developments. Accordingly, in order to ascertain whether South-African law and policy can successfully facilitate/enable sustainable development via the implementation of renewable energy, a specific methodology is proposed. In terms of the New Delhi Declaration of 2002 there are 7 principles of international law effecting sustainable development. These principles will be used as criteria in a principled assessment of South-African renewable energy law and policy in order to establish whether the goal of promoting sustainable development would be effected through the national policy developments.
Hexanic fraction of turmeric powder attenuates murine model of ...

African Journals Online (AJOL)

... of any detectable toxicity and sedative effects exerts pronounced peripheral and central antinociceptive effects, with no involvement of opioidergic system but possibly related to its ability to interact with TRPV1 receptors and the glutamatergic system. Keywords: Curcuma longa L., Antinociceptive, TRPV1, Glutamatergic ...
Sustainable Sizing.

Science.gov (United States)

Robinette, Kathleen M; Veitch, Daisy

2016-08-01

To provide a review of sustainable sizing practices that reduce waste, increase sales, and simultaneously produce safer, better fitting, accommodating products. Sustainable sizing involves a set of methods good for both the environment (sustainable environment) and business (sustainable business). Sustainable sizing methods reduce (1) materials used, (2) the number of sizes or adjustments, and (3) the amount of product unsold or marked down for sale. This reduces waste and cost. The methods can also increase sales by fitting more people in the target market and produce happier, loyal customers with better fitting products. This is a mini-review of methods that result in more sustainable sizing practices. It also reviews and contrasts current statistical and modeling practices that lead to poor fit and sizing. Fit-mapping and the use of cases are two excellent methods suited for creating sustainable sizing, when real people (vs. virtual people) are used. These methods are described and reviewed. Evidence presented supports the view that virtual fitting with simulated people and products is not yet effective. Fit-mapping and cases with real people and actual products result in good design and products that are fit for person, fit for purpose, with good accommodation and comfortable, optimized sizing. While virtual models have been shown to be ineffective for predicting or representing fit, there is an opportunity to improve them by adding fit-mapping data to the models. This will require saving fit data, product data, anthropometry, and demographics in a standardized manner. For this success to extend to the wider design community, the development of a standardized method of data collection for fit-mapping with a globally shared fit-map database is needed. It will enable the world community to build knowledge of fit and accommodation and generate effective virtual fitting for the future. A standardized method of data collection that tests products' fit methodically
Evaluation of the antinociceptive and anti-inflammatory effects of the acetone extract from Anacardium occidentale L

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Frederico Argollo Vanderlinde

2009-09-01

Full Text Available The stem bark of Anacardium occidentale L. (Anacardiaceae, commonly called cashew, is used in Brazilian traditional medicine for the treatment of gastric and inflammatory disorders. The present study was carried out to investigate the in vivo anti-inflammatory activities of the acetone extract (AE of the stem bark of A. occidentale. We evaluated the pharmacological activities of this plant material through the analgesic, antiedematogenic and chemotaxic inhibitory effects produced by the AE. The oral administration (p.o. of mice with the AE (0.1, 0.3 and 1.0 g/kg or positive control indomethacin (10 mg/kg inhibited acetic acid-induced writhing by 18.9, 35.9, 62.9 and 68.9%, respectively (ID50% = 530 mg/kg. The highest dose of the AE was able to inhibit croton oil-induced ear edema formation by 56.8% (indomethacin at 10 mg/kg, p.o. - 57.6% inhibition. When submitted to the carrageenan-induced peritonitis test, the AE (0.1, 0.3 and 1.0 g/kg, p.o. impaired leukocyte migration into the peritoneal cavity by 24.8, 40.5 and 49.6%, respectively. The positive control, dexamethasone (2 mg/kg, s.c., inhibited leukocyte migration by 66.9%. These results indicate the presence of anti-inflammatory and antinociceptive principles in the acetone extract of Anacardium occidentale, and reinforce the plant's potential therapeutic use against pain and inflammatory diseases.As cascas do caule do Anacardium occidentale L. (Anacardiaceae, conhecido como cajueiro, são popularmente utilizadas no Brasil para o tratamento de doenças gástricas e inflamatórias. Este estudo teve como objetivo a avaliação farmacológica in vivo da atividade antiinflamatória do extrato acetônico (AE obtido das cascas do A. occidentale, investigando os efeitos analgésico, antiedematogênico e inibitório sobre a quimiotaxia deste material botânico. A administração oral (p.o. em camundongos com o AE (0,1; 0,3 e 1 g/kg ou o controle positivo indometacina (10 mg/kg inibiu as contor
Sustainability or Bust: Malaysian Home Buyers’ Stated Preferences for Sus-Tainable Housing

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Syahid A.

2016-01-01

Full Text Available The lack of data on sustainable home buying behaviour in developing countries such as Malaysia is due to the absence of sustainable housing itself. However, it is still possible to solicit home buyers for their stated preferences and quantify its effects on housing demand. In this study, a sample of 300 responses to a Discrete Choice Experiment (DCE on sustainable housing features was analysed using the “support.CEs” program. This study found that the addition of sustainable features; renewable energy generation, enhanced soundproofing and ventilation, energy saving features, and higher green area ratios significantly increase home buyer’s willingness to pay (WTP for sustainable housing.
India's Proposed Universal Health Coverage Policy: Evidence for Age Structure Transition Effect and Fiscal Sustainability.

Science.gov (United States)

Narayana, Muttur Ranganathan

2016-12-01

India's High Level Expert Group on Universal Health Coverage in 2011 recommended a universal, public-funded and national health coverage policy. As a plausible forward-looking macroeconomic reform in the health sector, this policy proposal on universal health coverage (UHC) needs to be evaluated for age structure transition effect and fiscal sustainability to strengthen its current design and future implementation. Macroeconomic analyses of the long-term implications of age structure transition and fiscal sustainability on India's proposed UHC policy. A new measure of age-specific UHC is developed by combining the age profile of public and private health consumption expenditure by using the National Transfer Accounts methodology. Different projections of age-specific public health expenditure are calculated over the period 2005-2100 to account for the age structure transition effect. The projections include changes in: (1) levels of the expenditure as gross domestic product grows, (2) levels and shape of the expenditure as gross domestic product grows and expenditure converges to that of developed countries (or convergence scenario) based on the Lee-Carter model of forecasting mortality rates, and (3) levels of the expenditure as India moves toward a UHC policy. Fiscal sustainability under each health expenditure projection is determined by using the measures of generational imbalance and sustainability gap in the Generational Accounting methodology. Public health expenditure is marked by age specificities and the elderly population is costlier to support for their healthcare needs in the future. Given the discount and productivity growth rates, the proposed UHC is not fiscally sustainable under India's current fiscal policies except for the convergence scenario. However, if the income elasticity of public expenditure on social welfare and health expenditure is less than one, fiscal sustainability of the UHC policy is attainable in all scenarios of projected public
The Sustainability Cycle and Loop: models for a more unified understanding of sustainability.

Science.gov (United States)

Hay, Laura; Duffy, Alex; Whitfield, R I

2014-01-15

In spite of the considerable research on sustainability, reports suggest that we are barely any closer to a more sustainable society. As such, there is an urgent need to improve the effectiveness of human efforts towards sustainability. A clearer and more unified understanding of sustainability among different people and sectors could help to facilitate this. This paper presents the results of an inductive literature investigation, aiming to develop models to explain the nature of sustainability in the Earth system, and how humans can effectively strive for it. The major contributions are two general and complementary models, that may be applied in any context to provide a common basis for understanding sustainability: the Sustainability Cycle (S-Cycle), and the Sustainability Loop (S-Loop). Literature spanning multiple sectors is examined from the perspective of three concepts, emerging as significant in relation to our aim. Systems are shown to provide the context for human action towards sustainability, and the nature of the Earth system and its sub-systems is explored. Activities are outlined as a fundamental target that humans need to sustain, since they produce the entities both needed and desired by society. The basic behaviour of activities operating in the Earth system is outlined. Finally, knowledge is positioned as the driver of human action towards sustainability, and the key components of knowledge involved are examined. The S-Cycle and S-Loop models are developed via a process of induction from the reviewed literature. The S-Cycle describes the operation of activities in a system from the perspective of sustainability. The sustainability of activities in a system depends upon the availability of resources, and the availability of resources depends upon the rate that activities consume and produce them. Humans may intervene in these dynamics via an iterative process of interpretation and action, described in the S-Loop model. The models are briefly
The Sustainability Analysis Framework: An Effective Knowledge Communication Tool in a Whole of Government Context

Directory of Open Access Journals (Sweden)

Kendal Hodgman

2007-06-01

Full Text Available This paper focuses on the structural formation of the Sustainability Analysis Framework (SAF, which has proved to be an effective knowledge communication tool in the largest state administration in Australia, the Government of New South Wales. The SAF, devised by the author, has been implemented across thirty-eight state agencies and demonstrates that a whole of government Sustainability perspective is achievable. The level of the NSW Government's commitment to this process is evidenced by the fact that it was coordinated at the highest levels of the administration and engaged high-level input from a comprehensive portfolio of its agencies. The SAF's successful deployment across this significant bureaucracy shows that the generally applicable mechanism is effective in data collation, information sharing, knowledge organisation and the communication of Sustainability practice and wisdom. At the heart of the paper is the author's contention that one of the key problems which jeopardises our common future on Earth is the lack of effective tools to communicate Sustainability thinking and practice. In the course of the project, upon which this paper is based, the author identified the need for a visually and conceptually accessible mechanism to accelerate the uptake of Sustainability practice in a whole of organization context. In designing the SAF, which has successfully bridged this knowledge communication gap, the author employed two of humanity's fundamental learning tools – the diagram and the story.
Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

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Nadeson Raymond

2005-04-01

Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter
The Differential Effect of Sustained Operations on Psychomotor Skills of Helicopter Pilots.

Science.gov (United States)

McMahon, Terry W; Newman, David G

2018-06-01

Flying a helicopter is a complex psychomotor skill requiring constant control inputs from pilots. A deterioration in psychomotor performance of a helicopter pilot may be detrimental to operational safety. The aim of this study was to test the hypothesis that psychomotor performance deteriorates over time during sustained operations and that the effect is more pronounced in the feet than the hands. The subjects were helicopter pilots conducting sustained multicrew offshore flight operations in a demanding environment. The remote flight operations involved constant workload in hot environmental conditions with complex operational tasking. Over a period of 6 d 10 helicopter pilots were tested. At the completion of daily flying duties, a helicopter-specific screen-based compensatory tracking task measuring tracking accuracy (over a 5-min period) tested both hands and feet. Data were compared over time and tested for statistical significance for both deterioration and differential effect. A statistically significant deterioration of psychomotor performance was evident in the pilots over time for both hands and feet. There was also a statistically significant differential effect between the hands and the feet in terms of tracking accuracy. The hands recorded a 22.6% decrease in tracking accuracy, while the feet recorded a 39.9% decrease in tracking accuracy. The differential effect may be due to prioritization of limb movement by the motor cortex due to factors such as workload-induced cognitive fatigue. This may result in a greater reduction in performance in the feet than the hands, posing a significant risk to operational safety.McMahon TW, Newman DG. The differential effect of sustained operations on psychomotor skills of helicopter pilots. Aerosp Med Hum Perform. 2018; 89(6):496-502.
The Influence of Local Governance: Effects on the Sustainability of Bioenergy Innovation

Directory of Open Access Journals (Sweden)

Bianca Cavicchi

2017-03-01

Full Text Available This paper deals with processes and outcomes of sustainable bioenergy development in Emilia Romagna. It draws on an on-going research project concerning inclusive innovation in forest-based bioenergy and biogas in Norway, Sweden, Finland and Italy. The goal is to explore how local governance impacts on inclusive innovation processes and triple bottom sustainability of bioenergy development in Emilia Romagna and, ultimately, to contribute to the debate on the bioeconomy. It thus compares the case of biogas and forest-based bioenergy production. The study adopts an analytical framework called Grounded Innovation (GRIP and the local governance approach. The study uses qualitative methods and particularly semi-structured interviews and governance analysis. The key results show different outcomes on both inclusive innovation and triple bottom-line dimensions. Biogas has not fostered inclusiveness and triple bottom line sustainability benefits, contrary to forest-based bioenergy. The findings indicate that the minor role of local actors, particularly municipalities, in favour of industrial and national interests may jeopardise the sustainability of biobased industries. Besides, policies limited to financial incentives may lead to a land-acquisition rush, unforeseen local environmental effects and exacerbate conflicts.
International Conference on Effective Nuclear Regulatory Systems: Sustaining Improvements Globally. Book of Abstracts

International Nuclear Information System (INIS)

2016-01-01

The objective of this conference is to review and assess ways of further improving the effectiveness of regulatory systems for nuclear facilities and activities for both nuclear safety and nuclear security. The action items in the summary presented by the President of the conference held in 2013 in Ottawa, the lessons of the Fukushima Daiichi accident, the discussions at other international conferences and at international experts’ meetings conducted within the framework of the IAEA Action Plan on Nuclear Safety, as well as the CNS and the principles outlined in the Vienna Declaration on Nuclear Safety, will continue to have a significant impact on regulatory systems. All the aforementioned need to be taken into account to sustain improvements to regulatory systems. The expected outcomes of the conference are: - Enhanced safety and security of nuclear installations worldwide; - Challenges in regulating radiation sources and radioactive waste addressed; - Enhanced international cooperation for sustaining regulatory effectiveness; - Strengthened and sustained regulatory competence for nuclear safety and security; and - Strategies and actions for the future identified, as well as issues for consideration by governments, regulatory bodies and international organizations.
Effect of curcumin in mice model of vincristine-induced neuropathy.

Science.gov (United States)

Babu, Anand; Prasanth, K G; Balaji, Bhaskar

2015-06-01

Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity. The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model. Vincristine sulfate (0.1 mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14 d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10 mg/kg, p.o.) and curcumin (15, 30, and 60 mg/kg, p.o.) were administered for 14 consecutive days. Curcumin at 60 mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p Curcumin at 30 and 60 mg/kg exhibited significant changes (p Curcumin at 30 and 60 mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.
Sustaining an Effective ABC-ABM System

Directory of Open Access Journals (Sweden)

Gary COKINS

2011-02-01

Full Text Available The purpose of this paper is to describe the Activity- Based Costing (ABC and Activity-Based Management (ABM system and techniques to sustain them as a permanent and repeatable production reporting system, not just for one-off analysis. A comparison is made between ABC/ABM modeling software that extracts source data and business systems that include ABC/ABM modeling features. There are presented the stages of updating, running and rerunning the ABC/ABM system. The resulting information calculated and provided by the ABC/ABM system are analyzed and interpreted in terms of a multidimensional data analysis. The article ends with the authors' conclusions about the benefits of continued operation of sustaining the ABC/ABM system.
Enabling Effective Problem-oriented Research for Sustainable Development

Directory of Open Access Journals (Sweden)

Christoph Kueffer

2012-12-01

Full Text Available Environmental problems caused by human activities are increasing; biodiversity is disappearing at an unprecedented rate, soils are being irreversibly damaged, freshwater is increasingly in short supply, and the climate is changing. To reverse or even to reduce these trends will require a radical transformation in the relationship between humans and the natural environment. Just how this can be achieved within, at most, a few decades is unknown, but it is clear that academia must play a crucial role. Many believe, however, that academic institutions need to become more effective in helping societies move toward sustainability. We first synthesize current thinking about this crisis of research effectiveness. We argue that those involved in producing knowledge to solve societal problems face three particular challenges: the complexity of real-world sustainability problems, maintaining impartiality when expert knowledge is used in decision making, and ensuring the salience of the scientific knowledge for decision makers. We discuss three strategies to meet these challenges: conducting research in interdisciplinary teams, forming research partnerships with actors and experts from outside academia, and framing research questions with the aim of solving specific problems (problem orientation. However, we argue that implementing these strategies within academia will require both cultural and institutional change. We then use concepts from transition management to suggest how academic institutions can make the necessary changes. At the level of system optimization, we call for: quality criteria, career incentives, and funding schemes that reward not only disciplinary excellence but also achievements in inter-/transdisciplinary work; professional services and training through specialized centers that facilitate problem-oriented research and reciprocal knowledge exchange with society; and the integration of sustainability and inter
Effects of opioids in the formalin test in the Speke's hinged tortoise (Kinixy's spekii)

DEFF Research Database (Denmark)

Wambugu, SN; Towett, PK; Kiama, SG

2010-01-01

decrease in the duration of limb retraction in the formalin test. The anti-nociceptive effects were naloxone (5 mg/kg) reversible. The data suggest that the formalin test is a good test for studying nociception and anti-nociception in tortoises and that the opioidergic system plays a role in the control......Little is known about analgesia in lower vertebrates such as the Speke's hinged tortoise (Kinixy's spekii), yet of late they are increasingly being adopted as pets. The effects of morphine (5, 7.5, 10 and 20 mg/kg), pethidine (10, 20, and 50 mg/kg) and naloxone (5 mg/kg) on nociception induced...... by the formalin test (12.5%, 100 microL) were studied in the Speke's hinged tortoise. Formalin induced a monophasic limb retraction behavioural response and its duration was recorded. The behaviour lasted for 16.4 +/- 0.8 min. Morphine (7.5, 10 and 20 mg/kg) and pethidine (20 and 50 mg/kg) induced significant...
MEL-N16: A Series of Novel Endomorphin Analogs with Good Analgesic Activity and a Favorable Side Effect Profile.

Science.gov (United States)

Liu, Xin; Zhao, Long; Wang, Yuan; Zhou, Jingjing; Wang, Dan; Zhang, Yixin; Zhang, Xianghui; Wang, Zhaojuan; Yang, Dongxu; Mou, Lingyun; Wang, Rui

2017-10-18

Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are among the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications. Radioligand binding, cAMP accumulation, and β-arrestin-2 recruitment assays were employed to determine the activity of synthesized endomorphin analogs toward opioid receptors. The blood-brain barrier permeability and antinociceptive effect of these analogs were determined in several rodent models of acute and persistent pain. In addition, the side effects of the analogs were examined. The radioligand binding assay and functional activity examination indicated that the MEL-N16 series of compounds were more active agonists against μ opioid receptor than were the parent peptides. Notably, the analogs displayed biased downstream signaling toward G-protein pathways over β-arrestin-2 recruitment. The analogs showed highly potent antinociceptive effects in the tested nociceptive models. In comparison with endomorphins, the synthesized analogs were better able to penetrate the blood-brain barrier and exerted their pain regulatory activity in the central nervous system after peripheral injection. These analogs also have lower tendency to cause side effects than morphine does at similar or equal antinociceptive doses. The MEL-N16 compounds have highly potent and efficacious analgesic effects in various pain models with a favorable side effect profile.
Empirical Study on the Indicators of Sustainable Performance – the Sustainability Balanced Scorecard, Effect of Strategic Organizational Change

Directory of Open Access Journals (Sweden)

Maria Radu

2012-06-01

Full Text Available The sustainable organizational change has an ever increasing importance, leading to the rethinking of the management and systems of performance measurement and monitoring within the companies. As a reaction to current economic phenomena, in the first section of this work we tried to bring out the need for using the couple Balanced Scorecard - Corporate Social Responsibility by companies. Thus, companies involved in sustainable actions must grant a great importance to the impact of environmental, social and economic factors in providing added value, informing the interested parties and reflecting the reporting of sustainable performance. As a consequence, in the second part of the work we present the Sustainability Balanced Scorecard for the implementation of efficient strategies which cumulate the economic, social and environmental aspects as integrating system for sustainable performance and as a new challenge for organizational change. The key performance indicators included in the Sustainability Balanced Scorecard are quantified by the indicators of sustainable development, based on which the empirical research described in the third section of the work was achieved. Through the quantitative analysis of the economic and ecological indicators (Gross Domestic Product per capita, respective, Environmental Performance Index in correlation with the social indicator (Global Competitive Index, we conclude that the implementation of green strategies by companies leads to sustainable economic growth.
Review of sustainability indices and indicators: Towards a new City Sustainability Index (CSI)

Energy Technology Data Exchange (ETDEWEB)

Mori, Koichiro, E-mail: kmori@iis.u-tokyo.ac.jp [Institute of Industrial Science, University of Tokyo (Japan); Christodoulou, Aris, E-mail: aris.christodoulou@ucl.ac.uk [Centre for Transport Studies, University College London (United Kingdom)

2012-01-15

The purpose of this paper is to discuss conceptual requirements for a City Sustainability Index (CSI) and to review existing major sustainability indices/indicators in terms of the requirements. The following indices are reviewed: Ecological Footprint (EF), Environmental Sustainability Index (ESI), Dashboard of Sustainability (DS), Welfare Index, Genuine Progress Indicator (GPI), Index of Sustainable Economic Welfare, City Development Index, emergy/exergy, Human Development Index (HDI), Environmental Vulnerability Index (EVI), Environmental Policy Index (EPI), Living Planet Index (LPI), Environmentally-adjusted Domestic Product (EDP), Genuine Saving (GS), and some applications of composite indices or/and multivariate indicators to local or regional context as case studies. The key conceptual requirements for an adequate CSI are: (i) to consider environmental, economic and social aspects (the triple bottom line of sustainability) from the viewpoint of strong sustainability; (ii) to capture external impacts (leakage effects) of city on other areas beyond the city boundaries particularly in terms of environmental aspects; (iii) to create indices/indicators originally for the purpose of assessing city sustainability; and (iv) to be able to assess world cities in both developed and developing countries using common axes of evaluation. Based on the review, we conclude that it is necessary to create a new CSI that enables us to assess and compare cities' sustainability performance in order to understand the global impact of cities on the environment and human life as compared with their economic contribution. In the future, the CSI will be able to provide local authorities with guidance toward sustainable paths. - Highlights: Black-Right-Pointing-Pointer We derive the four key requirements for a new City Sustainability Index (CSI) system. Black-Right-Pointing-Pointer First, the triple bottom line must be considered in terms of strong sustainability. Black
Review of sustainability indices and indicators: Towards a new City Sustainability Index (CSI)

International Nuclear Information System (INIS)

Mori, Koichiro; Christodoulou, Aris

2012-01-01

The purpose of this paper is to discuss conceptual requirements for a City Sustainability Index (CSI) and to review existing major sustainability indices/indicators in terms of the requirements. The following indices are reviewed: Ecological Footprint (EF), Environmental Sustainability Index (ESI), Dashboard of Sustainability (DS), Welfare Index, Genuine Progress Indicator (GPI), Index of Sustainable Economic Welfare, City Development Index, emergy/exergy, Human Development Index (HDI), Environmental Vulnerability Index (EVI), Environmental Policy Index (EPI), Living Planet Index (LPI), Environmentally-adjusted Domestic Product (EDP), Genuine Saving (GS), and some applications of composite indices or/and multivariate indicators to local or regional context as case studies. The key conceptual requirements for an adequate CSI are: (i) to consider environmental, economic and social aspects (the triple bottom line of sustainability) from the viewpoint of strong sustainability; (ii) to capture external impacts (leakage effects) of city on other areas beyond the city boundaries particularly in terms of environmental aspects; (iii) to create indices/indicators originally for the purpose of assessing city sustainability; and (iv) to be able to assess world cities in both developed and developing countries using common axes of evaluation. Based on the review, we conclude that it is necessary to create a new CSI that enables us to assess and compare cities' sustainability performance in order to understand the global impact of cities on the environment and human life as compared with their economic contribution. In the future, the CSI will be able to provide local authorities with guidance toward sustainable paths. - Highlights: ► We derive the four key requirements for a new City Sustainability Index (CSI) system. ► First, the triple bottom line must be considered in terms of strong sustainability. ► Second, environmental leakage effects beyond city boundaries should

Assessing Capacity for Sustainability of Effective Programs and Policies in Local Health Departments.

Science.gov (United States)

Tabak, Rachel G; Duggan, Katie; Smith, Carson; Aisaka, Kristelle; Moreland-Russell, Sarah; Brownson, Ross C

2016-01-01

Sustainability has been defined as the existence of structures and processes that allow a program to leverage resources to effectively implement and maintain evidence-based public health and is important in local health departments (LHDs) to retain the benefits of effective programs. Explore the applicability of the Program Sustainability Framework in high- and low-capacity LHDs as defined by national performance standards. Case study interviews from June to July 2013. Standard qualitative methodology was used to code transcripts; codes were developed inductively and deductively. Six geographically diverse LHD's (selected from 3 of high and 3 of low capacity) : 35 LHD practitioners. Thematic reports explored the 8 domains (Organizational Capacity, Program Adaptation, Program Evaluation, Communications, Strategic Planning, Funding Stability, Environmental Support, and Partnerships) of the Program Sustainability Framework. High-capacity LHDs described having environmental support, while low-capacity LHDs reported this was lacking. Both high- and low-capacity LHDs described limited funding; however, high-capacity LHDs reported greater funding flexibility. Partnerships were important to high- and low-capacity LHDs, and both described building partnerships to sustain programming. Regarding organizational capacity, high-capacity LHDs reported better access to and support for adequate staff and staff training when compared with low-capacity LHDs. While high-capacity LHDs described integration of program evaluation into implementation and sustainability, low-capacity LHDs reported limited capacity for measurement specifically and evaluation generally. When high-capacity LHDs described program adoption, they discussed an opportunity to adapt and evaluate. Low-capacity LHDs struggled with programs requiring adaptation. High-capacity LHDs described higher quality communication than low-capacity LHDs. High- and low-capacity LHDs described strategic planning, but high
Assessing capacity for sustainability of effective programs and policies in local health departments

Science.gov (United States)

Tabak, Rachel G.; Duggan, Katie; Smith, Carson; Aisaka, Kristelle; Moreland-Russell, Sarah; Brownson, Ross C.

2015-01-01

Context Sustainability has been defined as the existence of structures and processes that allow a program to leverage resources to effectively implement and maintain evidence-based public health and is important in local health departments (LHDs) to retain the benefits of effective programs. Objective Explore the applicability of the Program Sustainability Framework in high- and low-capacity LHDs as defined by national performance standards. Design Case study interviews from June-July 2013. Standard qualitative methodology was used to code transcripts; codes were developed inductively and deductively. Setting Six geographically diverse LHD’s (selected from three high- and three low-capacity) Participants 35 LHD practitioners Main Outcome Measures Thematic reports explored the eight domains (Organizational Capacity, Program Adaptation, Program Evaluation, Communications, Strategic Planning, Funding Stability, Environmental Support, and Partnerships) of the Program Sustainability Framework. Results High-capacity LHDs described having environmental support, while low-capacity LHDs reported this was lacking. Both high- and low-capacity LHDs described limited funding; however, high-capacity LHDs reported greater funding flexibility. Partnerships were important to high- and low-capacity LHDs, and both described building partnerships to sustain programming. Regarding organizational capacity, high-capacity LHDs reported better access to and support for adequate staff and staff training compared to low-capacity LHDs. While high-capacity LHDs described integration of program evaluation into implementation and sustainability, low-capacity LHDs reported limited capacity for measurement specifically and evaluation generally. When high-capacity LHDs described program adoption, they discussed an opportunity to adapt and evaluate. Low-capacity LHDs struggled with programs requiring adaptation. High-capacity LHDs described higher quality communication than low-capacity LHDs. High
Neighborhood Sustainability Assessment: Evaluating Residential Development Sustainability in a Developing Country Context

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Tan Yigitcanlar

2015-03-01

Full Text Available Rapid urbanization, improved quality of life, and diversified lifestyle options have collectively led to an escalation in housing demand in our cities, where residential areas, as the largest portion of urban land use type, play a critical role in the formation of sustainable cities. To date there has been limited research to ascertain residential development layouts that provide a more sustainable urban outcome. This paper aims to evaluate and compare sustainability levels of residential types by focusing on their layouts. The paper scrutinizes three different development types in a developing country context—i.e., subdivision, piecemeal, and master-planned developments. This study develops a “Neighborhood Sustainability Assessment” tool and applies it to compare their sustainability levels in Ipoh, Malaysia. The analysis finds that the master-planned development, amongst the investigated case studies, possesses the potential to produce higher levels of sustainability outcomes. The results reveal insights and evidence for policymakers, planners, development agencies and researchers; advocate further studies on neighborhood-level sustainability analysis, and; emphasize the need for collective efforts and an effective process in achieving neighborhood sustainability and sustainable city formation.
Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice.

Science.gov (United States)

Miranda, Hugo F; Romero, Maria Asunción; Puig, Margarita M

2012-06-01

Preclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund's adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan's blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic inflammation (7 days after CFA). Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated. The isobolographic analysis revealed that in all groups of study (no inflammation, acute, and chronic inflammation), the combination of DEX : TRM was synergistic, for both the inhibition of nociception and the PE. The results suggest that the DEX : TRM (1 : 1) combination could be useful in the management of acute and chronic inflammatory musculoskeletal pains in humans; in addition, the synergistic interaction between the drugs observed both during acute and chronic inflammation suggests that less doses would be required of each drug to obtain effective analgesia. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.
Sustainability, the Greenhouse effect, silviculture, and overpopulation

International Nuclear Information System (INIS)

Hall, F.K.

1991-01-01

Ever since man became conscious of the finite dimensions of Planet Earth, he has worried about his ability to survive in an ever-more crowded environment. This paper reports that the fundamental question underlying this concern is sustainability: Can we indefinitely supply, maintain, and prolong that which we have? This question is, of course, multifaceted. Man's early concerns quickly polarized the scientists and economists of this world into two philosophical camps---the Malthusians and the Cornucopians. Over time, economists learned that Malthus seriously underestimated the capacity of technology to enhance productivity, although Malthusian sympathizers (both scientists and economists) continually raised the specter of imminent doom. Much of what lies ahead will provide a series of daunting challenges for us all, and the engine that drives sustainability has to be technology. The central issue is to ensure that the right kind of technology is available, and that it is used widely to ensure sustainability
Sustainability, the Greenhouse effect, silviculture, and overpopulation

Energy Technology Data Exchange (ETDEWEB)

Hall, F.K. (International Paper Co., Corporate Research Center, Tuxedo Park, NY (US))

1991-10-01

Ever since man became conscious of the finite dimensions of Planet Earth, he has worried about his ability to survive in an ever-more crowded environment. This paper reports that the fundamental question underlying this concern is sustainability: Can we indefinitely supply, maintain, and prolong that which we have This question is, of course, multifaceted. Man's early concerns quickly polarized the scientists and economists of this world into two philosophical camps---the Malthusians and the Cornucopians. Over time, economists learned that Malthus seriously underestimated the capacity of technology to enhance productivity, although Malthusian sympathizers (both scientists and economists) continually raised the specter of imminent doom. Much of what lies ahead will provide a series of daunting challenges for us all, and the engine that drives sustainability has to be technology. The central issue is to ensure that the right kind of technology is available, and that it is used widely to ensure sustainability.
Sustained-Paced Finger Tapping: A Novel Approach to Measure Internal Sustained Attention

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Marco A. Petilli

2018-05-01

Full Text Available Sustained attention is a fundamental prerequisite for all cognitive functions and its impairment is a common aftermath of both developmental and acquired neurological disorders. To date, all the sustained attention tasks rely heavily on selective attention to external stimuli. The interaction between selective and sustained attention represents a limit in the field of assessment and may mislead researchers or distort conclusions. The aim of the present perspective study was to propose a sustained version of the Paced Finger Tapping (S-PFT test as a novel approach to measure sustained attention that does not leverage external stimuli. Here, we administered S-PFT and other attentional tasks (visual sustained attention, visuospatial attention capacity, selective attention, and divided attention tasks to 85 adolescents. Thus, we provide evidence suggesting that S-PFT is effective in causing performance decrement over time, an important trademark of sustained attention tasks. We also present descriptive statistics showing the relationship between S-PFT and the other attentional tasks. These analyses show that, unlike visual sustained attention tests, performances to our task of internal sustained attention were not correlated to measures of selective attention and visuospatial attention capacity. Our results suggest that S-PFT could represent a promising and alternative tool both for empirical research and clinical assessment of sustained attention.
A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly

DEFF Research Database (Denmark)

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E

2016-01-01

of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. METHODS AND RESULTS: The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who...... on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). OBJECTIVE: The aim...... and sustainability. CONCLUSION: The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR....
Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial.

Science.gov (United States)

Stobaugh, Heather C; Bollinger, Lucy B; Adams, Sara E; Crocker, Audrey H; Grise, Jennifer B; Kennedy, Julie A; Thakwalakwa, Chrissie; Maleta, Kenneth M; Dietzen, Dennis J; Manary, Mark J; Trehan, Indi

2017-08-01

Background: Children who recover from moderate acute malnutrition (MAM) have high rates of relapse in the year after nutritional recovery. Interventions to decrease these adverse outcomes are needed to maximize the overall effectiveness of supplemental feeding programs (SFPs). Objective: We evaluated the effectiveness of a package of health and nutrition interventions on improving the proportion of children who sustained recovery for 1 y after MAM treatment. We further explored factors related to sustained recovery. Design: We conducted a cluster-randomized clinical effectiveness trial involving rural Malawian children aged 6-62 mo who were enrolled on discharge from an SFP for MAM. We enrolled 718 children at 10 control sites and 769 children at 11 intervention sites. In addition to routine health and nutrition counseling, the intervention group received a package of health and nutrition interventions that consisted of a lipid nutrient supplement, deworming medication, zinc supplementation, a bed net, and malaria chemoprophylaxis. A survival analysis was used to determine the effectiveness of the intervention as well as to identify factors associated with sustained recovery. Results: Of 1383 children who returned for the full 12-mo follow-up period, 407 children (56%) and 347 children (53%) sustained recovery in the intervention and control groups, respectively. There was no significant difference in relapse-free survival curves between the treatment and control groups ( P = 0.380; log-rank test). The risk factors for relapse or death after initial recovery were a smaller midupper arm circumference on SFP admission ( P = 0.01) and discharge ( P nutrition services in addition to traditional SFP treatment has no significant effect on improving sustained recovery in children after treatment of MAM. This trial was registered at clinicaltrials.gov as NCT02351687. © 2017 American Society for Nutrition.
Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Höglund, A Urban

2002-01-01

The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspi...
Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang).

Science.gov (United States)

Garrido, G; González, D; Delporte, C; Backhouse, N; Quintero, G; Núñez-Sellés, A J; Morales, M A

2001-02-01

Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from elevated stress. To assess its possible analgesic and antiinflammatory effects, the results of a standard extract evaluation are presented. Analgesia was determined using acetic acid-induced abdominal constriction and formalin-induced licking. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced oedema. Vimang (50-1000 mg/kg, p.o.) exhibited a potent and dose-dependent antinociceptive effect against acetic acid test in mice. The mean potency (DE(50)) was 54.5 mg/kg and the maximal inhibition attained was 94.4%. Vimang (20-1000 mg/kg, p.o.) dose-dependently inhibited the second phase of formalin-induced pain but not the first phase. The DE(50) of the second phase was 8.4 mg/kg and the maximal inhibition was 99.5%, being more potent than indomethacin at doses of 20 mg/kg. Vimang (20-1000 mg/kg, p.o.) significantly inhibited oedema formation (p Vimang could account for the antinociceptive and antiinflammatory actions reported here for the first time for M. indica bark aqueous extract. Copyright 2001 John Wiley & Sons, Ltd.
Antinociceptive And Antiinflammatory Effects Of Essential Oil Of ...

African Journals Online (AJOL)

mediated both centrally as well as peripherally, while the antiinflammatory activity may be effective in both early and late phases of inflammation. The results obtained may therefore be used to rationalize the use of the plant in the treatment of pain and fever in traditional medicine. Keywords: Dennettia tripetala, Essential Oil, ...
Sustainability index for Taipei

International Nuclear Information System (INIS)

Lee, Y.-J.; Huang Chingming

2007-01-01

Sustainability indicators are an effective means of determining whether a city is moving towards sustainable development (SD). After considering the characteristics of Taipei, Taiwan, discussions with experts, scholars and government departments and an exhaustive literature review, this study selected 51 sustainability indicators corresponding to the socio-economic characteristic of Taipei City. Such indicators should be regarded as a basis for assessing SD in Taipei City. The 51 indicators are classified into economic, social, environmental and institutional dimensions. Furthermore, statistical data is adopted to identify the trend of SD from 1994 to 2004. Moreover, the sustainability index is calculated for the four dimensions and for Taipei as a whole. Analysis results demonstrate that social and environmental indicators are moving towards SD, while economic and institutional dimensions are performing relatively poorly. However, since 2002, the economic sustainability index has gradually moved towards SD. Overall, the Taipei sustainability index indicates a gradual trend towards sustainable development during the past 11 years
Strategic Leadership of Corporate Sustainability

DEFF Research Database (Denmark)

Strand, Robert

2014-01-01

Strategic leadership and corporate sustainability have recently come together in conspicuously explicit fashion through the emergence of top management team (TMT) positions with dedicated corporate sustainability responsibilities. These TMT positions, commonly referred to as 'Chief Sustainability......? What effects do corporate sustainability TMT positions have at their organizations? We consider these questions through strategic leadership and neoinstitutional theoretical frameworks. Through the latter, we also engage with Weberian considerations of bureaucracy. We find that the reasons why...
A comparison between effectiveness of three types of music on memory activity and sustained attention in schizophrenic patients

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Narges bahmany

2014-10-01

Full Text Available Background: schizophrenia is a psychiatric disorder in which a lot of cognitive functions including memory, attention, motor skills, executive functions and intelligence are compromised. Numerous empirical studies showed that schizophrenic patients have problem in sustain retention and memory activity. The objective of this study was a comparison between effectiveness of three types of music on memory activity and sustain retention in schizophrenic patients. Material and Methods: A total of 60 schizophrenic patients (30 males , 30 females 18-48 years old were selected from available sampling frame. Participants were otherwise healthy except for schizophrenia. Wechsler Memory Scale and cognitive diagnostic battery Kay test were taken from all subjects. Then patients were randomly divided into three experimental groups (Iranian classic, western classic and pop music and three control groups. There were 10 participants (5 male, 5 female in each group. After taking these tests, music therapy course was performed on experimental groups. After music therapy sessions were completed, tests were taken again from groups. Results: Covariance analysis results indicated that music therapy is overall effective on memory activity. But type of music had no effect in improving memory activity. There wasn’t significant difference between groups considering type of music. Furthermore, covariance analysis showed that music therapy is totally effective on sustain retention and type of music is effective in this intervention. Pop music had the most effectiveness on schizophrenic patients in improving sustain retention. Conclusion: Performing music therapy improves memory and retention. More over, using pop music particularly has the most effect in improving sustain retention in schizophrenic patients.
Sustaining the Effects of Gatekeeper Suicide Prevention Training.

Science.gov (United States)

Shtivelband, Annette; Aloise-Young, Patricia A; Chen, Peter Y

2015-02-23

Background: Gatekeeper training is a promising suicide prevention strategy that is growing in popularity. Although gatekeeper training programs have been found to improve trainee knowledge, self-efficacy, and perceived skills, researchers have found that the benefit of gatekeeper training may not last over time. Aims: The purpose of this study was to identify strategies for strengthening the long-term effects of suicide prevention gatekeeper training. Method: In-depth interviews and focus groups were conducted with gatekeepers (N = 44) and data were analyzed using a qualitative research approach. Results: The results of this study suggest that posttraining interventions may be more effective if they include the following seven themes: (a) social network - connecting with other gatekeepers; (b) continued learning - further education; (c) community outreach - building awareness; (d) accessibility - convenience; (e) reminders - ongoing communication; (f) program improvement -- enhancing previous training; and (g) certification - accreditation. Conclusion: Posttraining interventions that incorporate the themes from this study offer a promising direction in which to sustain the effects of gatekeeper suicide prevention training.
ICT innovations for sustainability

CERN Document Server

Aebischer, Bernard

2015-01-01

ICT Innovations for Sustainability is an investigation of how information and communication technology can contribute to sustainable development. It presents clear definitions of sustainability, suggesting conceptual frameworks for the positive and negative effects of ICT on sustainable development. It reviews methods of assessing the direct and indirect impact of ICT systems on energy and materials demand, and examines the results of such assessments. In addition, it investigates ICT-based approaches to supporting sustainable patterns of production and consumption, analyzing them at various levels of abstraction – from end-user devices, Internet infrastructure, user behavior, and social practices to macro-economic indicators. Combining approaches from Computer Science, Information Systems, Human-Computer Interaction, Economics, and Environmental Sciences, the book presents a new, holistic perspective on ICT for Sustainability (ICT4S). It is an indispensable resource for anyone working in the area of ICT...
R&D Cooperation and Knowledge Spillover Effects for Sustainable Business Innovation in the Chemical Industry

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Petr Hájek

2018-04-01

Full Text Available This paper investigates the influence of research and development (R&D cooperation on the creation of spillover effects for sustainable firms in the chemical industry. We explore the evidence for the origin of knowledge spillovers derived from cooperation amongst firms and universities and R&D organizations as well as to test the influence of internal/external financial support on these effects. The results confirm that when firms acquire knowledge from internal sources, this leads to increased innovation and sustainable performance. We have proved that internal expenditure results in increased internal knowledge spillovers. These findings may be specific for Central and Eastern (CEE transition countries, indicating their efforts to build path-dependent structures based on knowledge institutions and businesses as well as knowledge networks. However, this study also provides a more “global” contribution to the knowledge spillover effect theory. It shows that a firm’s cooperation both with universities and with other firms promotes different types of knowledge spillovers and can affect diverse modes of sustainable activities in innovation.
Sustainability.

Science.gov (United States)

Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

2016-10-01

This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.
Effect of Gmelina arborea Roxb in experimentally induced inflammation and nociception

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Yogesh A Kulkarni

2013-01-01

Full Text Available Background: Gmelina arborea Roxb (Verbenaceae, also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE and methanol extracts (ME of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01 and 8.2 ± 1.24 (P < 0.01 respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3% as compared to ME (77.9% in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.

Exploring the effectiveness of sustainable water management structures in the Upper Pungwe river basin

Science.gov (United States)

Nyikadzino, B.; Chibisa, P.; Makurira, H.

The study endeavoured to assess the effectiveness of stakeholder structures and their participation in sustainable water resources management in the Upper Pungwe river basin shared by Zimbabwe and Mozambique. The study sought to assess the level and effectiveness of stakeholder, gender and the vulnerable groups representation in sustainable water resources management as well as the whole stakeholder participation process. The study employed both qualitative and quantitative methods for data collection and analysis. Sampling data was obtained from 15 stakeholder representatives (councillors) constituting Pungwe Subcatchment Council, 30 water users ranging from small scale to large scale users and professionals in water resources management. Two different questionnaires and three structured interviews were administered during the study. Water permit database, financial reports and other source documents were also analysed. The study established that the sustainability and effectiveness of stakeholder structures and their participation in water resources management is being compromised by lack of stakeholder awareness. Water utilisation is very high in the subcatchment (99%) while women participation is still low (20%). The study therefore recommends the use of quotas for the participation of women in stakeholder structures. Stakeholder structures are encouraged to intensify stakeholder awareness on issues of river protection, efficient water use and pollution control. Further research is recommended to be carried out on the effectiveness of stakeholder structures in combating water pollution and enhancing river protection.
Pharmacological evidence favouring the traditional use of the root bark of Condalia buxifolia Reissek in the relief of pain and inflammation in mice.

Science.gov (United States)

Simões, Róli R; Coelho, Igor S; Junqueira, Stella C; Maldaner, Graciela; Morel, Ademir F; Venzke, Dalila; Ruani, Ana Paula; Pizzolatti, Moacir G; Zanchet, Eliane M; Santos, Adair R S

2015-12-04

The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and against dysentery. This study was designed to investigate whether the methanolic extract of the root bark of Condalia buxifolia (MECb) exhibits antinociceptive and anti-inflammatory effects in mice. Furthermore, also was investigated the involvement of glutamatergic and opioidergic system in the antinociceptive effect induced by MECb. The antinociceptive and anti-inflammatory effects of intra-gastric gavage (i.g.) administered MECb (10-300 mg/kg) were evaluated in mice subjected to chemical (formalin, acetic-acid, glutamate) or thermal (hot plate) models of pain. The involvement of opioid system in the antinociceptive effect of the MECb was investigated in formalin test. Furthermore, a nonspecific effect of MECb was evaluated by measuring locomotor activity and exploratory behavior in open field test. Finally, was performed a phytochemical analysis of MECb. The phytochemical analysis of MECb was performed through HPLC analysis showing that the alkaloid Condaline-A is the main constituent. The intragastric administration of MECb (100-300 mg/kg) significantly inhibited the nociception caused by acetic acid (48 ± 2%), inflammatory phase (49 ± 3%) and paw edema (32 ± 6) caused by formalin, and MECb (100mg/kg, i.g.) also inhibited nociception caused by glutamate (41 ± 7%). In addition, MECb (100-300 mg/kg, i.g.) increased the paw withdrawal latency in hot-plate test, without affecting the locomotor activity and exploratory behavior in open field test. Finally, the antinociceptive effects of MECb (100mg/kg, i.g.) were significantly reversed by naloxone (1mg/kg, i.p.) in the formalin test. These data show, for the first time, that MECb has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system and the activation of opioid mechanism, besides present central effects. These
The mediating effect of sustainability control system on reverse ...

African Journals Online (AJOL)

This paper analyses part of the viability of green supply chain management practices created for fisheries industry to implement sustainability control system adoption as mediating on reverse logistics innovation and customer environmental collaboration towards sustainability performance. It examines reverse logistics ...
Towards Sustainable Health Care Organizations

Directory of Open Access Journals (Sweden)

Mauro ROMANELLI

2017-09-01

Full Text Available Health care organizations have to develop a sustainable path for creating public value by seeking legitimacy for building and maintaining public trust with patients as social and economic institutions creating value and sustaining both health and wealth for people and communities within society. Health care organizations having at disposal decreasing resources and meeting increasing demands of citizens are following an unsustainable path. Designing sustainable health care systems and organizations is emerging as a strategic goal for developing the wealth of people and communities over time. Building sustainable organizations relies on valuing human resources, designing efficient and effective processes, using technology for better managing the relationships within and outside organizations. Sustainable health care organizations tend to rediscover the importance of human resource management and policies for effectively improving communication with patients and building trust-based relationships. While processes of accreditation contribute to legitimizing effectiveness and quality of health care services and efficient processes, introducing and using new information and communication technologies (ICTs and informatics helps communication leading to restore trust-based relationships between health care institutions and patients for value creation within society.
Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

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Katarzyna Popiolek-Barczyk

2014-01-01

Full Text Available Nociceptin/orphanin FQ (N/OFQ antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP, was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p., a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.. Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.
A Research on Class Teachers Related to Determining the Effects of Consumers’ Personal Values on Sustainable Consumption Behavior

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Rıdvan Karalar

2010-06-01

Full Text Available The world’s sources about to running out have been realised as a result of that population increase and economic development to be lived in the twentieth century have caused the transformation from the notion of unlimited economic development to sustainable development notion. Sustainable development is a model that predicts existing generation satisfies their needs without that next generation’s satisfy their need. Projection of sustainable development on marketing area have been actualized by means of coming up with sustainable marketing approach. Sustainable marketing approach predict to create sustainable solutions by adding conformity with eco-system in addition to achieving organizational goals and satisfy consumers’ needs which traditional marketing’s goals. The target of sustainable development notion in regard of consumption is to be accepted sustainable consumption behavior. It requires inquiring factors affecting behavior in question because sustainable consumption pattern to be accepted and spread to the world. In the study examined that individual values affecting sustainable consumption behavior of class teacher who work at elementary schools in Kutahya, Merkez. The findings indicate the significant effect of universalism and security values type in sustainable consumption behavior. Also, it is found that frequency of sustainable consumption behavior is mid-level. The results of this research have significant implications for stakeholders of sustainable consumption and future research.
Synergism between COX-3 inhibitors in two animal models of pain.

Science.gov (United States)

Muñoz, J; Navarro, C; Noriega, V; Pinardi, G; Sierralta, F; Prieto, J C; Miranda, H F

2010-04-01

The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test. The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice. Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain. These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.
A pathway to a more sustainable water sector: sustainability-based asset management.

Science.gov (United States)

Marlow, D R; Beale, D J; Burn, S

2010-01-01

The water sectors of many countries are faced with the need to address simultaneously two overarching challenges; the need to undertake effective asset management coupled with the broader need to evolve business processes so as to embrace sustainability principles. Research has thus been undertaken into the role sustainability principles play in asset management. As part of this research, a series of 25 in-depth interviews were undertaken with water sector professionals from around Australia. Drawing on the results of these interviews, this paper outlines the conceptual relationship between asset management and sustainability along with a synthesis of the relevant opinions voiced in the interviews. The interviews indicated that the participating water authorities have made a strong commitment to sustainability, but there is a need to facilitate change processes to embed sustainability principles into business as usual practices. Interviewees also noted that asset management and sustainability are interlinked from a number of perspectives, especially in the way decision making is undertaken with respect to assets and service provision. The interviews also provided insights into the research needed to develop a holistic sustainability-based asset management framework.
Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: their anti-inflammatory and anti-nociceptive activities.

Science.gov (United States)

Shafi, Syed; Alam, Mohammad Mahboob; Mulakayala, Naveen; Mulakayala, Chaitanya; Vanaja, G; Kalle, Arunasree M; Pallu, Reddanna; Alam, M S

2012-03-01

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. Copyright Â© 2012 Elsevier Masson SAS. All rights reserved.
Sustaining Engagement and Interest in the Classroom: Effects of the EngageALL Instructional Model

Science.gov (United States)

Larson, Sue C.

2014-01-01

This chapter describes an empirical study that tests the motivational and learning effects of an intervention designed to initiate and sustain interest and engagement in high school biology classrooms. Positive effects were demonstrated for conceptual understanding, vocabulary acquisition, and perceptions of the learning experiences. [This article…
Sustainable development and energy indicators

International Nuclear Information System (INIS)

Pop-Jordanov, Jordan

2002-01-01

Starting from the basic definition of sustainable development and its four dimensions, the role of indicators for sustainable energy development is analysed. In particular, it is shown that important energy efficiency indicators belong in fact to energy supply efficiency, while the end-use energy efficiency could be more pertinently represented by energy intensity indicators. Furthermore, the negentropic effects of science and technology related sustainable energy scenarios are pointed out. Finally, the sustainable development is related to wisdom, interpreted as a sum of knowledge, morality and timing. (Author)
Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

Science.gov (United States)

Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

2011-01-01

Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.
Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

Directory of Open Access Journals (Sweden)

Merab G Tsagareli

2011-07-01

Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.
Effectiveness and sustainability of the ViSC Social Competence Program to prevent cyberbullying and cyber-victimization: Class and individual level moderators.

Science.gov (United States)

Gradinger, Petra; Yanagida, Takuya; Strohmeier, Dagmar; Spiel, Christiane

2016-01-01

We investigated whether the general anti-bullying program ViSC sustainably prevents cyberbullying and cyber-victimization. A longitudinal randomized control group design was used to examine (i) program effectiveness immediately after a 1 year implementation phase and (ii) sustainable program effects 6 months later taking several moderators on the class level (class climate and ethnic diversity) and on the individual level (gender, age, internet usage, traditional bullying/victimization) into account. Effectiveness (e.g., the change between waves 2 and 1) was examined in 2,042 students (47.6% girls), aged 11.7 years (SD = 0.88) enrolled in 18 schools and 103 classes. Sustainability (e.g., the change between waves 3 and 2) was examined in a sub-sample of 6 schools and 35 classes comprising 659 students. The self-assessment multiple-item scales showed longitudinal and multiple group invariance. Factor scores were extracted to compute difference scores for effectiveness (Posttest minus Pretest) and sustainability (Follow-up test minus Posttest) for cyberbullying and cyber-victimization. Multilevel Modeling was applied to examine (i) the effectiveness and (ii) the sustainability of the ViSC intervention controlling for several individual and class level variables. Controlling for covariates, it was demonstrated that the ViSC program is effective in preventing cyberbullying and cyber-victimization and that the effects are sustainable after 6 months. The consequences for cyberbullying prevention are discussed. © 2016 Wiley Periodicals, Inc.
Effectiveness of community-based mangrove management for sustainable resource use and livelihood support

NARCIS (Netherlands)

Damastuti, Ekaningrum; Groot, de Dolf

2017-01-01

Community-Based Mangrove Management (CBMM) is implemented with different approaches and outcomes. This study examined the effectiveness of various CBMM practices to achieve sustainable management of mangrove resources. We analyzed local mangrove resource management strategies in four coastal
Sustainability, Transformational Leadership, and Social Entrepreneurship

Directory of Open Access Journals (Sweden)

Etayankara Muralidharan

2018-02-01

Full Text Available This article examines the extent to which culturally endorsed transformational leadership theories (CLTs and the sustainability of society, both considered societal level institutional indicators, impact the emergence of social entrepreneurship. Using 107,738 individual-level responses from 27 countries for the year 2009 obtained from the Global Entrepreneurship Monitor (GEM survey, and supplementing with country-level data obtained from Global Leadership and Organizational Behavior Effectiveness (GLOBE and Sustainability Society Foundation (SSF, our findings from multilevel analysis show that transformational CLTs and sustainability conditions of society positively influence the likelihood of individuals becoming social entrepreneurs. Further, the effectiveness of transformational CLTs matters more for social entrepreneurship when the sustainability of society is low, which suggests the interaction between cultural leadership styles and societal sustainability. This article contributes to comparative entrepreneurship research by introducing strong cultural antecedents of social entrepreneurship in transformational CLTs and societal sustainability. We discuss various implications and limitations of our study, and we suggest directions for future research.
THE CORRELATION BETWEEN SUSTAINABLE PERFORMANCE MEASURES AND ORGANIZATIONAL SUSTAINABILITY IN THE BRAZILIAN CONTEXT

Directory of Open Access Journals (Sweden)

RODRIGO GOYANNES GUSMÃO CAIADO

2016-12-01

Full Text Available Over the past few years, issues of sustainability are gaining greater prominence among organizations and their stakeholders around the world and with it the effective measurement of environmental performance has been a challenge for sustainable transition. The purpose of the article is to analyse, through the the perception of market experts and researchers, what sustainable performance measures have stronger positive correlation to achieve organizational sustainability in order to help employees in making decisions that reduce the consumption of resources and that create value throughout its chain. The research is of an exploratory and descriptive nature, with qualitative and quantitative method and has a deductive logic. It aims to help professionals and academics who want to start the measurement and continuous improvement of economic, environmental, social, governance and technical performance of their organizations. Finally, the analyzes allow direct efforts to sustainable measures considered most important, allowing the transition of the organization for sustainability.
Sustainable diets within sustainable food systems.

Science.gov (United States)

Meybeck, Alexandre; Gitz, Vincent

2017-02-01

Sustainable diets and sustainable food systems are increasingly explored by diverse scientific disciplines. They are also recognised by the international community and called upon to orient action towards the eradication of hunger and malnutrition and the fulfilment of sustainable development goals. The aim of the present paper is to briefly consider some of the links between these two notions in order to facilitate the operationalisation of the concept of sustainable diet. The concept of sustainable diet was defined in 2010 combining two totally different perspectives: a nutrition perspective, focused on individuals, and a global sustainability perspective, in all its dimensions: environmental, economic and social. The nutrition perspective can be easily related to health outcomes. The global sustainability perspective is more difficult to analyse directly. We propose that it be measured as the contribution of a diet to the sustainability of food systems. Such an approach, covering the three dimensions of sustainability, enables identification of interactions and interrelations between food systems and diets. It provides opportunities to find levers of change towards sustainability. Diets are both the results and the drivers of food systems. The drivers of change for those variously involved, consumers and private individuals, are different, and can be triggered by different dimensions (heath, environment, social and cultural). Combining different dimensions and reasons for change can help facilitate the transition to sustainable diets, recognising the food system's specificities. The adoption of sustainable diets can be facilitated and enabled by food systems, and by appropriate policies and incentives.
Enhancing Effective Stakeholder Participation in Local Groundwater Sustainability Planning through Technical Assistance in California

Science.gov (United States)

Weintraub, C.; Christian-Smith, J.; Dobbin, K.; Cullen, K.

2017-12-01

This presentation will share content from UCS's new publication, Getting Involved in Groundwater; A Guide to Effective Engagement in California's Groundwater Sustainability Plans, as well as lessons learned from collaborating with community organizations to provide technical assistance to Groundwater Sustainability Agency (GSA) board members and stakeholders in the San Joaquin Valley on Groundwater Sustainability Plan (GSP) development. California's Sustainable Groundwater Management Act (SGMA) mandates extensive stakeholder engagement, presenting an opportunity for unincorporated, low-income communities that have historically been affected by but not included in water decisions. However, implementation requires a concerted, thoughtful effort. Through technical assistance and strategic outreach, the Union of Concerned Scientists (UCS) is working to ensure stakeholder engagement in GSP development is robust, diverse, and supported by the best science available. UCS created the GSP stakeholder engagement guide to equip GSA members, scientists and interested community members to meaningfully engage in the GSP development process. The guide serves as a technical primer on SGMA's GSP process and as a resource for understanding groundwater management in California. The guide is just one component of a larger effort to overcome barriers to effective engagement in sustainable groundwater management, especially those presented by technical information. In April, UCS co-hosted a technical assistance workshop for GSA and advisory committee members in Visalia, CA with the Community Water Center (CWC), a local environmental justice non-profit. The workshop was well received and UCS and the CWC were invited to host a second workshop in June. To deepen this engagement and provide one-on-one technical assistance, UCS developed a program to match relevant water experts in the UCS Science Network with GSA members or involved community members in need of specific technical support
In the Name of Sustainability

DEFF Research Database (Denmark)

Rasmussen, Louise Mubanda

2017-01-01

of ethnographic fieldwork with NGOs supporting ‘orphans and vulnerable children’ in Malawi, this article explores the practices, social relations and contradictory effects that the vision of sustainability engenders. The article illustrates how the commitment to sustainability paradoxically produces practices...... that can only be sustained through continuous flows of donor funding. It argues that the persistence of sustainability as an organising principle is connected both to its self-confirming logic and to the ways in which practices of ‘sustainability’ shape the subjectivities of local brokers and come...

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