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Sample records for spinal antinociceptive effects

  1. Enhanced Inhibitory Synaptic Transmission in the Spinal Dorsal Horn Mediates Antinociceptive Effects of TC-2559

    National Research Council Canada - National Science Library

    Cheng, Long-Zhen; Han, Lei; Fan, Jing; Huang, Lan-Ting; Peng, Li-Chao; Wang, Yun

    2011-01-01

    ...) 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...

  2. Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test.

    Science.gov (United States)

    Onifer, Stephen M; Reed, William R; Sozio, Randall S; Long, Cynthia R

    2015-01-01

    Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n = 12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n = 12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1-5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P < 0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted.

  3. Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test

    Directory of Open Access Journals (Sweden)

    Stephen M. Onifer

    2015-01-01

    Full Text Available Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM, requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5 vertebra of isoflurane-anesthetized experimental rats (n=12 beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n=12 underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P<0.001. The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted.

  4. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain.

    Science.gov (United States)

    Hama, Aldric T; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-12-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na(+) channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na(+) channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggest that peripherally expressed Na(+) channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    Science.gov (United States)

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

  6. Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons.

    Science.gov (United States)

    Hong, Bin; Yao, LingLing; Ni, Linhui; Wang, Li; Hu, XingYue

    2017-08-15

    The use of botulinum toxin A (BTX-A) for various clinical therapeutic applications is increasing. It is widely believed that peripheral therapeutic or toxic effects of BTX-A are exclusively mediated by SNAP-25 cleavage. There is growing evidence of long-distance retrograde axonal transport of BTX-A on entering the central nervous system, subsequent to a local injection of the toxin. However, the prevalence of central antinociceptive effects after BTX-A peripheral application and its underlying mechanisms are unclear. Our results show that (1) BTX-A can undergo retrograde axonal transport to the dorsal horn after peripheral application; (2) Peripheral pretreatment with BTX-A decreases the expression and function of AMPA receptors in the spinal cord dorsal horn neurons; (3) Peripheral pretreatment with BTX-A does not change basal glutamate release, but decreases the effect of formalin-evoked release of glutamate in spinal cord dorsal horn neurons. These results suggest that peripheral application of BTX-A can change AMPA receptor expression in, and glutamate release from, spinal dorsal horn neurons, which may have significance in its central antinociceptive effects. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Immediate effects of spinal manipulative therapy on regional antinociceptive effects in myofascial tissues in healthy young adults.

    Science.gov (United States)

    Srbely, John Z; Vernon, Howard; Lee, David; Polgar, Miranda

    2013-01-01

    The purpose of this study was to investigate if spinal manipulative therapy (SMT) can evoke immediate regional antinociceptive effects in myofascial tissues by increasing pressure pain thresholds (PPTs) over myofascial trigger points in healthy young adults. A total of 36 participants (19 men, 17 women; age, 28.0 [5.3] years; body mass index, 26.5 [5.7] kg/m(2)) with clinically identifiable myofascial trigger points in the infraspinatus and gluteus medius muscles were recruited from the University of Guelph, Ontario, Canada. Participants were randomly allocated to 2 groups. Participants in the test group received chiropractic SMT targeted to the C5-C6 spinal segment. Participants in the control group received sham SMT. The PPT was recorded from the right infraspinatus and gluteus medius muscles at baseline (preintervention) and 1, 5, 10, and 15 minutes postintervention. Three participants were disqualified, resulting in a total of 33 participants analyzed. Significant increases in the PPT (decreased pain sensitivity) were observed in the test infraspinatus group when compared with test gluteus medius, control infraspinatus, and control gluteus medius groups (P .05). This study showed that SMT evokes short-term regional increases in PPT within myofascial tissues in healthy young adults. Copyright © 2013 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  8. Fatty acid amide hydrolase (FAAH inhibitors exert pharmacological effects, but lack antinociceptive efficacy in rats with neuropathic spinal cord injury pain.

    Directory of Open Access Journals (Sweden)

    Aldric T Hama

    Full Text Available Amelioration of neuropathic spinal cord injury (SCI pain is a clinical challenge. Increasing the endocannabinoid anandamide and other fatty acid amides (FAA by blocking fatty acid amide hydrolase (FAAH has been shown to be antinociceptive in a number of animal models of chronic pain. However, an antinociceptive effect of blocking FAAH has yet to be demonstrated in a rat model of neuropathic SCI pain. Four weeks following a SCI, rats developed significantly decreased hind paw withdrawal thresholds, indicative of below-level cutaneous hypersensitivity. A group of SCI rats were systemically treated (i.p. with either the selective FAAH inhibitor URB597 or vehicle twice daily for seven days. A separate group of SCI rats received a single dose (p.o. of either the selective FAAH inhibitor PF-3845 or vehicle. Following behavioral testing, levels of the FAA N-arachidonoylethanolamide, N-oleoyl ethanolamide and N-palmitoyl ethanolamide were quantified in brain and spinal cord from SCI rats. Four weeks following SCI, FAA levels were markedly reduced in spinal cord tissue. Although systemic treatment with URB597 significantly increased CNS FAA levels, no antinociceptive effect was observed. A significant elevation of CNS FAA levels was also observed following oral PF-3845 treatment, but only a modest antinociceptive effect was observed. Increasing CNS FAA levels alone does not lead to robust amelioration of below-level neuropathic SCI pain. Perhaps utilizing FAAH inhibition in conjunction with other analgesic mechanisms could be an effective analgesic therapy.

  9. Mechanisms of the influence of midazolam on morphine antinociception at spinal and supraspinal levels in rats.

    Science.gov (United States)

    Luger, T J; Hayashi, T; Lorenz, I H; Hill, H F

    1994-12-27

    The mechanisms for the combined antinociceptive effect of midazolam and morphine administered at spinal (intrathecal, i.t.) and supraspinal (intracerebroventricular, i.c.v.) levels were investigated in rats. Nociceptive test results showed that co-administration of midazolam and morphine at the spinal level potentiated morphine-induced antinociception, and that this interaction was blocked by intraperitoneal (i.p.) naloxone and reversed by i.t. bicuculline and i.p. flumazenil. Also, bicuculline and flumazenil blocked midazolam-induced antinociception at the spinal level, and naloxone completely reversed morphine antinociception. In contrast, when drugs were injected intracerebroventricularly, midazolam inhibited the antinociceptive effect of morphine (as determined by the hot-plate test). The inhibitory effects of i.c.v. midazolam upon i.c.v. morphine antinociception were partly blocked by flumazenil and bicuculline. Midazolam-induced antinociception was increased by bicuculline and decreased by flumazenil; naloxone i.p. blocked both i.c.v. morphine antinociception and i.c.v. morphine-midazolam antinociception. Results after i.t. injection may be due to an interaction between morphine and midazolam/GABAA receptor-activated systems. At the supraspinal level, this interaction may also activate other systems that are distinct from those governing the individual action of each agonist.

  10. Dopamine D3 receptor dysfunction prevents anti-nociceptive effects of morphine in the spinal cord

    Directory of Open Access Journals (Sweden)

    Kori L Brewer

    2014-06-01

    Full Text Available Dopamine (DA modulates spinal reflexes, including nociceptive reflexes, in part via the D3 receptor subtype. We have previously shown that mice lacking the functional D3 receptor (D3KO exhibit decreased paw withdrawal latencies from painful thermal stimuli. Altering the DA system in the CNS, including D1 and D3 receptor systems, reduces the ability of opioids to provide analgesia. Here, we tested if the increased pain sensitivity in D3KO might result from a modified µ-opioid receptor (MOR function at the spinal cord level. As D1 and D3 receptor subtypes have competing cellular effects and can form heterodimers, we tested if the changes in MOR function may be mediated in D3KO through the functionally intact D1 receptor system.We assessed thermal paw withdrawal latencies in D3KO and wild type (WT mice before and after systemic treatment with morphine, determined MOR and phosphorylated MOR (p-MOR protein expression levels in lumbar spinal cords, and tested the functional effects of DA and MOR receptor agonists in the isolated spinal cord.In vivo, a single morphine administration (2 mg/kg increased withdrawal latencies in WT but not D3KO, and these differential effects were mimicked in vitro, where morphine modulated spinal reflex amplitudes (SRAs in WT but not D3KO. Total MOR protein expression levels were similar between WT and D3KO, but the ratio of phosphorylated MOR (pMOR/total MOR was higher in D3KO. Blocking D3 receptors in the isolated WT cord precluded morphine’s inhibitory effects observed under control conditions. Lastly, we observed an increase in D1 receptor protein expression in the lumbar spinal cord of D3KO.Our data suggest that the D3 receptor modulates the MOR system in the spinal cord, and that a dysfunction of the D3 receptor can induce a morphine-resistant state. We propose that the D3KO mouse may serve as a model to study the onset of morphine resistance at the spinal cord level, the primary processing site of the

  11. Antinociceptive effects of lacosamide on spinal neuronal and behavioural measures of pain in a rat model of osteoarthritis.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2014-12-23

    Alterations in voltage-gated sodium channel (VGSC) function have been linked to chronic pain and are good targets for analgesics. Lacosamide (LCM) is a novel anticonvulsant that enhances the slow inactivation state of VGSCs. This conformational state can be induced by repeated neuronal firing and/or under conditions of sustained membrane depolarisation, as is expected for hyperexcitable neurones in pathological conditions such as epilepsy and neuropathy, and probably osteoarthritis (OA). In this study, therefore, we examined the antinociceptive effect of LCM on spinal neuronal and behavioural measures of pain, in vivo, in a rat OA model. OA was induced in Sprague Dawley rats by intraarticular injection of 2 mg of monosodium iodoacetate (MIA). Sham rats received saline injections. Behavioural responses to mechanical and cooling stimulation of the ipsilateral hind paw and hindlimb weight-bearing were recorded. In vivo electrophysiology experiments were performed in anaesthetised MIA or sham rats, and we recorded the effects of spinal or systemic administration of LCM on the evoked responses of dorsal horn neurones to electrical, mechanical (brush, von Frey, 2 to 60 g) and heat (40°C to 50°C) stimulation of the peripheral receptive field. The effect of systemic LCM on nociceptive behaviours was assessed. Behavioural hypersensitivity ipsilateral to knee injury was seen as a reduced paw withdrawal threshold to mechanical stimulation, an increase in paw withdrawal frequency to cooling stimulation and hind limb weight-bearing asymmetry in MIA-treated rats only. Spinal and systemic administration of LCM produced significant reductions of the electrical Aβ- and C-fibre evoked neuronal responses and the mechanical and thermal evoked neuronal responses in the MIA group only. Systemic administration of LCM significantly reversed the behavioural hypersensitive responses to mechanical and cooling stimulation of the ipsilateral hind paw, but hind limb weight-bearing asymmetry

  12. 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

  13. Antinociceptive effect of Pleurotus ostreatus (Oyster Mushroom ...

    African Journals Online (AJOL)

    Hot water at 550C was used to determine the nociceptive responses of the animals to detect anti-nociceptive effects of Pleurotus ostreatus extracts as compared to the control in hot water inflicted pain. The results suggested that Pleurotus ostreatus aqueous extract exhibits antinociceptive properties against thermal stimulus ...

  14. Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

    Science.gov (United States)

    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.

  15. Antinociceptive Profile of Levo-tetrahydropalmatine in Acute and Chronic Pain Mice Models: Role of spinal sigma-1 receptor.

    Science.gov (United States)

    Kang, Dong-Wook; Moon, Ji-Young; Choi, Jae-Gyun; Kang, Suk-Yun; Ryu, Yeonhee; Park, Jin Bong; Lee, Jang-Hern; Kim, Hyun-Woo

    2016-12-02

    We have recently reported that repeated systemic treatments of extract from Corydalis yanhusuo alleviate neuropathic pain and levo-tetrahydropalmatine (l-THP) is one of active components from Corydalis. We designed this study to investigate antinociceptive effect of l-THP in acute and chronic pain models and related mechanism within the spinal cord. We found that intraperitoneal pretreatment with l-THP significantly inhibited the second phase of formalin-induced pain behavior. In addition, intrathecal as well as intraperitoneal pretreatment with l-THP reduced the mechanical allodynia (MA) induced by direct activation of sigma-1 receptor (Sig-1). In chronic constriction injury mice, these treatments remarkably suppressed the increase in MA and spinal phosphorylation of the NMDA receptor NR1 subunit expression on day 7 after surgery. Intrathecal treatment with l-THP combined with the Sig-1R antagonist, BD1047 synergistically blocked MA suggesting that l-THP modulates spinal Sig-1R activation. CatWalk gait analysis also supported that antinociceptive effect of l-THP as demonstrated by restoration of percentages of print area and single stance. Meanwhile, intrathecal pretreatment with naloxone, non-selective opioid receptor antagonist, did not affect the effect of l-THP. In conclusion, these results demonstrate that l-THP possesses antinociceptive effects through spinal Sig-1R mechanism and may be a useful analgesic in the management of neuropathic pain.

  16. Reversal by naloxone of the spinal antinociceptive actions of a systemically-administered NSAID.

    Science.gov (United States)

    Herrero, J. F.; Headley, P. M.

    1996-01-01

    1. Possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and endogenous opioids were examined in electrophysiological experiments in alpha-chloralose anaesthetized spinalized rats without or with carrageenan-induced acute inflammation of one hindpaw. Spinal reflex responses, monitored as single motor unit discharges, were elicited by noxious pinch and electrical stimuli. 2. The mu-opioid agonist, fentanyl, was an effective depressant of reflexes under all conditions (ED50 6-14 micrograms kg-1, i.v.). In rats without peripheral inflammation the NSAID, flunixin, a niflumic acid derivative, had only a small effect that was not dose-dependent. However, in animals with unilateral inflammation, flunixin reduced spinal reflexes evoked both by noxious pinch stimuli (that activate peripheral nociceptors; ID50 4 mg kg-1, i.v.) and by electrical stimuli (that bypass nociceptor endings; ID50 6.5- 11 mg kg-1, i.v.), indicating that it has a central site of action at doses comparable to those used clinically. 3. The opioid antagonist, naloxone (1 mg kg-1, i.v.), reversed all actions of fentanyl. It did not reverse the small effects that flunixin had in rats without inflammation, showing that the NSAID is not a direct opioid agonist. In rats with carrageenan-induced inflammation of the hindpaw, however, naloxone fully reversed or prevented the antinociception by flunixin, but not that by the alpha 2-adrenoceptor agonist, medetomidine. 4. We conclude that under conditions of peripheral inflammation and the resultant central changes, the NSAID, flunixin, has antinociceptive actions that are mediated by endogenous opioids acting within the spinal cord. Images Figure 1 Figure 3 PMID:8799570

  17. 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.

  18. Synergistic antinociceptive effects of alfentanil and propofol in the formalin test.

    Science.gov (United States)

    Jia, Na; Zuo, Xiaochun; Guo, Chao; Li, Yuwen; Cui, Jia; Zhao, Chao; Cao, Shanshan; Wang, Chao; Li, Ruili; Wu, Yin; Wen, Aidong

    2017-04-01

    The present study was conducted to determine the combined analgesic effect of alfentanil and propofol in the formalin test. Diluted formalin was injected into the dorsal surface of the right hind paw in rats. Nociceptive behavior was determined by counting the number of flinches of the injected paw for 1 h after injection; a reduction in formalin‑induced flinching was interpreted as an antinociceptive effect. Isobolographic analysis was used to determine the type of antinociceptive interaction (additivity, antagonism or synergism). Extracellular signal‑regulated kinase (ERK) and c‑fos protein levels were also detected by western blot analysis to determine the potential mechanisms of the synergistic effect. Alfentanil, propofol or an alfentanil‑propofol combination had an antinociceptive effect in the formalin test. The median effective dose (ED50), value of the individual drug was also obtained. The derived theoretical ED50 for the antinociceptive effect (4.36 mg/kg) was different from the observed experimental ED50 value (2.51 mg/kg). The interaction between alfentanil and propofol that produced the antinociceptive effect was synergistic according to isobolographic analysis. Furthermore, the combination of alfentanil and propofol treatments may produce synergistically antinociceptive effects by inhibiting the phosphorylation of ERK1/2 and decreasing the expression of c‑fos in the spinal cord. These results demonstrated that combined treatment, with alfentanil and propofol, produced synergistic antinociceptive effects in the formalin test and may have therapeutic potential for the treatment of acute pain.

  19. Antinociceptive Effect of Promethazine in Mice

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    Amir Farshchi

    2009-09-01

    Full Text Available Objective(sThe present study was undertaken to investigate the nociception activity of promethazine, a tranquillizer devoid of hypnotic activity in mice.Materials and MethodsAntinociception was evaluated, using the acetic acid-induced writhing, tail flick, hot plate and formalin pain tests.ResultsPromethazine (4 and 6 mg/kg and acetylsalicylic acid (100 mg/kg produced a significant inhibition of the second phase response in the formalin pain model (P0.05 and administration of naloxone (0.1 mg/kg couldn't block the antinociceptive effect of promethazine.ConclusionThe data obtained suggest that antinociceptive effects of the promethazine may be mediated via peripheral and not central mechanisms.

  20. 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

  1. Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude

    Science.gov (United States)

    Gerhold, Katharina J.; Drdla-Schutting, Ruth; Honsek, Silke D.; Forsthuber, Liesbeth

    2015-01-01

    Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg−1, buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg−1), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis. PMID:26134641

  2. Antinociceptive effect of Pleurotus ostreatus (Oyster Mushroom ...

    African Journals Online (AJOL)

    PROF HORSFALL

    aqueous extracts and group five treated with 15 mg/kg Aspirin (a standard drug) as positive control. Hot water at 550C was used to determine the nociceptive responses of the animals to detect anti-nociceptive effects of Pleurotus ostreatus extracts as compared to the control in hot water inflicted pain. The results suggested ...

  3. Curcumin attenuates morphine antinociceptive tolerance through suppressing up-regulation of spinal Toll-like receptor 4 in rats

    Directory of Open Access Journals (Sweden)

    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

  4. The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level.

    Science.gov (United States)

    Farkas, Ibolya; Tuboly, Gabor; Benedek, Gyorgy; Horvath, Gyongyi

    2011-10-01

    The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB(1)) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. Intrathecal injection of either EM (0.03-10 μg) or NADA (1.5-50 μg) caused dose-dependent antihyperalgesia, but NADA was 5.4 times less potent than EM. The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB(1) antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB(1) receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Anti-nociceptive effect of stigmasterol in mouse models of acute and chronic pain.

    Science.gov (United States)

    Walker, Cristiani Isabel Banderó; Oliveira, Sara Marchesan; Tonello, Raquel; Rossato, Mateus Fortes; da Silva Brum, Evelyne; Ferreira, Juliano; Trevisan, Gabriela

    2017-08-18

    Stigmasterol is a common sterol found in plants, but the anti-nociceptive effect of this compound and its mechanism of action are not fully explored. Thus, in the present study, the anti-nociceptive effect of stigmasterol was investigated in acute and chronic models of pain and its mechanism of action. We used adult male albino Swiss mice (25-35 g) to observe the anti-nociceptive effect of stigmasterol in acetic-acid writhing test or in complete Freund's adjuvant injection, surgical incision in hind paw, or partial sciatic nerve ligation. Moreover, we investigate the involvement of opioid receptors (naloxone, 2 mg/kg, intraperitoneally) in stigmasterol anti-nociceptive effect and stigmasterol action on acetylcholinesterase activity. Some possible adverse effects caused by stigmasterol were also investigated. Stigmasterol (0.3-3 mg/kg, orally) exhibited an anti-nociceptive effect on acetic-acid-induced writhing test. Furthermore, it markedly attenuated the mechanical allodynia caused by surgical incision (after acute treatment with stigmasterol, preventive and curative effects were observed) and partial sciatic nerve ligation (after acute treatment with stigmasterol) and complete Freund's adjuvant (after acute or repeated treatment with stigmasterol). The anti-nociceptive effect of stigmasterol was not reversed by naloxone. Moreover, stigmasterol did not alter in vitro acetylcholinesterase activity in spinal cord or brain samples. Also, stigmasterol did not cause gastric ulcers or alter the gastrointestinal transit of mice. Taken together, these results support the potential anti-nociceptive effect of stigmasterol in different models of pain.

  6. 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.

    Science.gov (United States)

    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 (mGluR1) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). Differential signaling by mGluR1, 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 mGluR1 activator (i.e., endogenous biased agonism at mGluR1) 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 varies

  7. Antinociceptive and respiratory effects of nalbuphine in rhesus monkeys.

    Science.gov (United States)

    Gerak, L R; Butelman, E R; Woods, J H; France, C P

    1994-11-01

    Antinociceptive and respiratory effects of nalbuphine and other opioids were studied in rhesus monkeys. In a thermal, tail withdrawal assay, the kappa agonist enadoline and the mu agonists alfentanil and fentanyl produced maximum antinociceptive effects in all subjects and over a wide range of temperatures, whereas nalbuphine produced antinociceptive effects in only some subjects and only when the water temperature was < or = 50 degrees C. Naltrexone antagonized the antinociceptive effects of nalbuphine, alfentanil and enadoline; however, the magnitude of antagonism was not equal among agonists. In subjects that did not show an antinociceptive response to nalbuphine, nalbuphine (3.2-10.0 mg/kg) antagonized the antinociceptive effects of fentanyl but not enadoline. The irreversible opioid antagonist clocinnamox produced a parallel shift to the right in the nalbuphine dose-effect curve 1 hr after administration and decreased the maximum effect produced by nalbuphine 24 and 48 hr after administration. Nalbuphine had modest respiratory-depressant effects in monkeys breathing air and attenuated hyperventilation produced by 5% CO2. In contrast, alfentanil had marked respiratory-depressant effects in monkeys breathing air or 5% CO2 in air and these effects were antagonized by nalbuphine. Taken together, these results suggest nalbuphine has low efficacy at mu opioid receptors; however, quantitative differences between alfentanil and nalbuphine indicate a second (non-enadoline sensitive) receptor might also be important for the antinociceptive effects of nalbuphine.

  8. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    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.

  9. [Synergism of caffeine on antinociceptive effects of metamizole].

    Science.gov (United States)

    Díaz-Reval, María Irene; Galván-Orozco, Renato; López-Muñoz, Francisco Javier; Carrillo-Munguía, Norma

    2008-01-01

    Combinations of analgesic drugs have been used as an option for treating pain because some types of pain are difficult to relieve with conventional analgesics. This group of drugs has been combined with analgesics or drugs without analgesic effect and is called adjuvant. One such drug is caffeine. We undertook the present study to analyze if caffeine is able to potentiate the antinociceptive effect of metamizole in the formalin model. Metamizole produced a dose-dependent antinociceptive effect with ED(50) = 329.61 mg/kg in the formalin model. Caffeine at the following doses (3.16, 10.0, 17.8 and 31.6 mg/kg) also showed antinociceptive effect. When a subeffective dose of metamizole (100 mg/kg) was combined with caffeine (3.16, 10.0, 17.8 or 31.6 mg/kg), higher antinociceptive effects were produced than the corresponding effects produced by metamizole alone. One combination presented potentiation effect; the other combination showed antinociceptive effect that was not different from the effects of metamizole alone. Two combinations showed an effect lower than the corresponding effect produced by metamizole alone. Adjuvant caffeine is able to change the effect of metamizole in the inflammatory pain model, in which caffeine also presents an antinociceptive effect.

  10. Central antinociceptive effect of tapentadol is increased by nitric oxide synthase inhibitors.

    Science.gov (United States)

    Bujalska-Zadrożny, Magdalena; Wolińska, Renata; Leśniak, Anna; Sacharczuk, Mariusz

    2016-10-01

    Nitric oxide synthases (NOSs) have been shown to participate in the mechanism of the antinociceptive action of tapentadol. The results obtained in this study indicate that tapentadol administered intrathecally at a range of doses (30-100 µg) increased nociceptive thresholds in the Randall-Selitto and tail-flick tests in rats; however, this effect was significant only for the higher doses. After intracerebroventricular administration of tapentadol at the same dose range, an antinociceptive effect was observed only in response to mechanical stimuli. In coadministration studies, L-N-nitro arginine (L-NOArg) - a nonselective NOS inhibitor as well as selective inhibitors: 7-Nitroindazole (7-NI), L-N(1-iminoethyl)lysine (L-NIL) or N-(1-iminoethyl)-L-ornithine (L-NIO) for the respective neuronal, inducible, and endothelial NOSs enhanced the antinociceptive activity of intrathecally administered tapentadol in the Randall-Selitto test and to a lesser extent in the tail-flick test. A similar, although less pronounced effect of intracerebroventricular tapentadol was also observed after previous administration of NOS inhibitors in the Randall-Selitto test, but not in the tail-flick test. In conclusion, neuronal NOS, inducible NOS, and endothelial NOS influence the antinociceptive action of tapentadol at the spinal level and to a much lesser extent at the supraspinal level.

  11. Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    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.

  12. Effect of estrogen on morphine- and oxycodone-induced antinociception in a female femur bone cancer pain model.

    Science.gov (United States)

    Ono, Hiroko; Nakamura, Atsushi; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Shinohara, Shunji

    2016-02-15

    Although estrous cycle has been reported to influence antiociceptive effect of morphine in several pain conditions, its effect on cancer pain is not well established. We investigated the effect of estrogen on morphine antinociception using a bone cancer pain model and compared its potency with that of oxycodone. Female mice were ovariectomized (OVX) for preparation of a femur bone cancer pain (FBC) model. β-estradiol was subcutaneously (s.c.) administered and antinociceptive effects of opioids was assessed using the von Frey monofilament test. Although morphine (5-20mg/kg, s.c.) did have significant antinociceptive effects in the FBC-OVX group, its effects in the FBC-OVX+β-estradiol (OVX+E) group was limited. Oxycodone (1-5mg/kg, s.c.) exhibited significant effects in both groups. Expression changes in opioid-related genes (μ-, κ-, δ-opioid receptors, prodynorphin, proenkephalin, proopiomelanocortin) in the spinal and supraspinal sites were examined among the sham-OVX, sham-OVX+E, FBC-OVX, and FBC-OVX+E groups by in situ hybridization. These studies detected a significant increase in prodynorphin in the spinal dorsal horn of the FBC-OVX+E group. Spinal injection of a dynorphin-A antibody to FBC-OVX+E mice restored antinociception of morphine. In conclusion, we detected a differential effect of estrogen on morphine- and oxycodone-induced antinociception in a female FBC model. The effect of morphine was limited with estrogen exposure, which may be due to estrogen- and pain-mediated spinal expression of dynorphin-A. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Evaluation of the Antinociceptive Effect of the Ethanolic Extract of ...

    African Journals Online (AJOL)

    HPLC analysis revealed the presence of gallic acid, ellagic acid and Punicalagins A&B. Conclusion: The results demonstrated that ethanol pomegranate extract has an antinociceptive effect that may be related to the presence of identified phytochemicals. Key words: Pain, ethanolic extract of pomegranate, analgesia, ...

  14. Peripheral antinociceptive effects of morphine after burn injury

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    In a double-blind study, 2 mg of morphine in saline, or saline only, was given subcutaneously into a second-degree bilateral leg-burn injury in 12 volunteers. Heat-pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration. These results confirm exp...... experimental data demonstrating a peripheral antinociceptive effects of opioids in inflamed tissue....

  15. Antinociceptive and anti-Inflammatory effects of the standardized oil ...

    African Journals Online (AJOL)

    The effect of Callistemon lanceolatus (Syn. C. citrinus curtis; Family: Myrtaceae) leaf oil was studied for the antinociceptive and anti-inflammatory activity in experimental animals. C. lanceolatus, 25 – 100 mg/kg administered orally for 3 days exhibited graded dose response equivalent to 21.95% - 89.90% protection in the tail ...

  16. Chemical composition and antinociceptive effects of essential oil ...

    African Journals Online (AJOL)

    Purpose: To investigate the antinociceptive effect of the essential oil from the aerial parts of Gundelia. tournefortii (EOGT) in various experimental models. Methods: The essential oil from the aerial parts of Gundelia tournefortii was extracted using steam distillation method median lethal dose (LD50) of EOGT was evaluated ...

  17. Treatment with Sulforaphane Produces Antinociception and Improves Morphine Effects during Inflammatory Pain in Mice.

    Science.gov (United States)

    Redondo, Alejandro; Chamorro, Pablo Aníbal Ferreira; Riego, Gabriela; Leánez, Sergi; Pol, Olga

    2017-12-01

    The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ-opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain. Results showed that treatment with SFN inhibited allodynia and hyperalgesia induced by CFA and increased the local antinociceptive actions of morphine. This treatment also augmented the expression of Nrf2, HO-1, NQO1, and MOR, and inhibited NOS2 and CD11b/c overexpression and MAPK phosphorylation induced by inflammation. Thus, this study shows that the induction of Nrf2 might inhibit inflammatory pain and enhance the analgesic effects of morphine by inhibiting oxidative stress and inflammatory responses induced by peripheral inflammation. This study suggests the administration of SFN alone and in combination with morphine are potential new ways of treating chronic inflammatory pain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Antinociceptive effects of Cremophor EL orally administered to mice

    Directory of Open Access Journals (Sweden)

    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.

  19. Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain.

    Science.gov (United States)

    Hao, Wei; Chen, Lei; Wu, Li-Fang; Yang, Fan; Niu, Jian-Xiang; Kaye, Alan D; Xu, Shi-Yuan

    2016-01-01

    Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). To assess the antinociceptive effect of TSN IIA on CIBP. A randomized, double-blind, controlled animal trial was performed. University lab in China. A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain

  20. Ascending nociceptive control contributes to the antinociceptive effect of acupuncture in a rat model of acute pain.

    Science.gov (United States)

    Tobaldini, Glaucia; Aisengart, Betina; Lima, Marcelo M S; Tambeli, Claudia H; Fischer, Luana

    2014-04-01

    Acupuncture-induced analgesia depends on the activation of endogenous pain modulation pathways. In this study, we asked whether ascending nociceptive control (ANC), a form of pain-induced analgesia, contributes to the antinociceptive effect of acupuncture. To answer this question, we tested the ability of procedures that block ANC-induced analgesia, at peripheral, spinal, nucleus accumbens and rostral ventral medulla levels, to block acupuncture-induced analgesia. Acupuncture at ST36 (Zusanli), a widely used acupoint located in the hind limb, induced potent heterosegmental antinociception in the orofacial formalin test. The magnitude of this antinociceptive effect was similar to that induced by an intraplantar injection of capsaicin, a procedure classically used to activate ANC. The antinociceptive effect of acupuncture was blocked by sciatic C-fibers depletion (1% perineural capsaicin), spinal administration of a μ-opioid (Cys2,Tyr3,Orn5,Pen7amide, .2 μg) or of a GABAA (bicuculline, .3 μg) receptor antagonist, intra-nucleus accumbens administration of a μ-opioid receptor antagonist (Cys2,Tyr3,Orn5,Pen7amide, 1 μg), or intrarostral ventral medulla administration of a nicotinic acetylcholine receptor antagonist (mecamylamine, .6 μg). In addition, acupuncture at ST36 and/or upper lip formalin induced c-Fos expression in the nucleus accumbens and in rostral ventral medulla. On the basis of these results, we propose that ANC contributes to the antinociceptive effect of acupuncture. This article presents a novel mechanism of acupuncture analgesia, contributing to the understanding of its scientific basis. Because ANC is a pain modulation pathway activated by peripheral noxious stimulation that ascends to supraspinal regions, it could be the link between acupoint stimulation and the central mechanisms underlying acupuncture analgesia. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Evaluation of antinociceptive effects of Tragia plukenetii: A possible mechanism

    Science.gov (United States)

    Venkatesh, Sama; Fatima, Saba

    2013-01-01

    Tragia plukenetii R.Smith. (Euphorbiaceae) is an erect, prostate herb with sparsely hispid stinging hairs. In the present study, ethanolic extract and its fractions of T. plukenetii aerial parts were evaluated for antinociceptive and central nervous system (CNS) depressant effects. Among all the extracts, chloroform extract has produced significant analgesic activity at a test dose of 250 mg/kg in acetic acid induced writhing test and Eddy's hotplate test. The analgesic effect of chloroform extract (68.83% inhibition) is comparable with aspirin (72.09% inhibition) in acetic acid induced writhing test. Chloroform extract significantly increased the latency time in hotplate test. In the study of CNS depressant effect, the chloroform extract was found to produce a significant (P < 0.01) reduction of the exploratory capacity and depressant effect in locomotor activity. From the point of CNS depressant and good protective effect on chemical and thermal pain stimuli, indicates that T. plukenetii chloroform extract may have morphinomimetic properties. The naloxone is not able to alter the T. plukenetii induced antinociceptive effect in writhing and hotplate test. Thus, the observed antinociceptive activity of T. plukenetii might have resulted from the activation of peripheral receptors. PMID:24501531

  3. Synthesis, antinociceptive and anti-inflammatory effects of porphyrins.

    Science.gov (United States)

    Alonso-Castro, Angel Josabad; Zapata-Morales, Juan Ramón; Hernández-Munive, Abigail; Campos-Xolalpa, Nimsi; Pérez-Gutiérrez, Salud; Pérez-González, Cuauhtémoc

    2015-05-15

    Porphyrins are natural compounds with several biological activities. We report the synthesis and the evaluation of the anti-inflammatory and antinociceptive effects of 4 porphyrins: 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetra(4'-fluorophenyl)porphyrin (TpFPP), 5,10,15,20-tetra(4'-chlorophenyl)porphyrin (TpClPP), and 5,10,15,20-tetra(4'-bromophenyl)porphyrin (TpBrPP). The in vitro anti-inflammatory effects were evaluated on heat-induced hemolysis. The antinociceptive effects were evaluated using the hot plate and formalin tests. The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema. The anti-arthritic effects were evaluated using carrageenan kaolin induced arthritis (CKIA). All porphyrins inhibited hemolysis with similar potency than naproxen (NPX). In the antinociceptive tests, all porphyrins tested at 200mg/kg showed similar effects compared to 100mg/kg NPX. In the in vivo anti-inflammatory acute assay, only three porphyrins (TPP, TpFPP and TpBrPP) decreased inflammation with similar activity than 2mg/ear indomethacin (IND). Further anti-inflammatory experiments were carried out with TPP, TpFPP and TpBrPP. In the in vivo anti-inflammatory chronic assay, porphyrins decreased inflammation with similar activity than 8mg/kg IND. Porphyrins tested at 200mg/kg showed anti-arthritic effects. The antinociceptive, anti-inflammatory and arthritic activities of porphyrins suggest that these compounds might be a good alternative for the treatment of inflammatory diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Anti-inflammatory and Antinociceptive Effects of the Alcoholic Extract ...

    African Journals Online (AJOL)

    Anti-inflammatory and Antinociceptive Effects of the Alcoholic Extract of Indian Polygala arvensis in Experimental Animals. ... time in the hot plate method by 69.55% (p < 0.01) and 107.13% (p < 0.001) respectively as well as in analgesymeter-induced mechanical pain by 28.84% (p < 0.5) and 55.71% (p < 0.05) respectively.

  5. Morphine and Clonidine Combination Therapy Improves Therapeutic Window in Mice: Synergy in Antinociceptive but Not in Sedative or Cardiovascular Effects

    Science.gov (United States)

    Stone, Laura S.; German, Jonathan P.; Kitto, Kelly F.; Fairbanks, Carolyn A.; Wilcox, George L.

    2014-01-01

    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 efficacy over

  6. 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

  7. Antinociceptive effect of amygdalin isolated from Prunus armeniaca on formalin-induced pain in rats.

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    Hwang, Hye-Jeong; Kim, Pil; Kim, Chang-Ju; Lee, Hye-Jung; Shim, Insop; Yin, Chang Shik; Yang, Young; Hahm, Dae-Hyun

    2008-08-01

    Amygdalin is a plant glucoside isolated from the stones of rosaceous fruits, such as apricots, peaches, almond, cherries, and plums. To investigate the pain-relieving activity of amygdalin, we induced pain in rats through intraplantar injection of formalin, and evaluated the antinociceptive effect of amygdalin at doses of 0.1, 0.5, 1.0, and 10.0 mg/kg-body weight by observing nociceptive behavior such as licking, biting and shaking, the number of Fos-immunoreactive neurons in the spinal cord, and the mRNA expression of inflammatory cytokines in the plantar skin. The intramuscular injection of amygdalin significantly reduced the formalin-induced tonic pain in both early (the initial 10 min after formalin injection) and late phases (10-30 min following the initial formalin injection). During the late phase, amygdalin did reduce the formalin-induced pain in a dose-dependent manner in a dose range less than 1 mg/kg. Molecular analysis targeting c-Fos and inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) also showed a significant effect of amygdalin, which matched the results of the behavioral pain analysis. These results suggest that amygdalin is effective at alleviating inflammatory pain and that it can be used as an analgesic with anti-nociceptive and anti-inflammatory activities.

  8. 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.

  9. An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats

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    Sekiguchi Miho

    2008-12-01

    Full Text Available Abstract Background Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomaized (OVX rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study. Methods We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5, the sham-CT (n = 5, and the OVX-CT-pcpa (n = 5 groups recieved calcitonin (CT: 4 U/kg/day, while OVX-vehi (n = 5 and the sham-vehi (n = 5 groups received vehicle subcutaneously 5 times a week for 4 weeks. The OVX-CT-pcpa-group was given traperitoneal injection of p-chlorophenylalanine (pcpa; an inhibitor of serotonin biosynthesis (100 mg/kg/day in the last 3 days of calcitonon injection. Two hours after 5% formalin (0.05 ml subcutaneously into the hind paw, the L5 spinal cord were removed and the number of Fos-immunoreactive (ir neurons were evaluated using the Mann-Whitney-U test. Results The numbers of Fos-ir neurons in the OVX-CT and sham-CT groups were significantly less than in the OVX-vehi and sham-vehi groups, respectively (p = 0.0090, p = 0.0090. The number of Fos-ir neurons in the OVX-CT-pcpa-group was significantly more than that of the OVX-CT-group (p = 0.0283, which means pcpa inhibits calcitonin induced reduction of c-Fos production. Conclusion The results in this study demonstrated that 1 the increase of c-Fos might be related to hyperalgesia in OVX-rats. 2 Calcitonin has

  10. Anti-nociceptive effect of total alkaloids isolated from the seeds of ...

    African Journals Online (AJOL)

    The antinociceptive effect of the extract in mice was evaluated by acetic acid writhing reflex test, hot plate test, capsaicin-induced nociception test, tail-flick test and formalin-induced pain test in mice. Furthermore, pretreatment of the animals with naloxone (2 mg/kg) was performed to investigate whether the antinociceptive ...

  11. Discriminative stimulus and antinociceptive effects of dihydroetorphine in rhesus monkeys.

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    Gerak, Lisa R; Gauthier, Cheryl R A; France, Charles R A P

    2003-04-01

    Although dihydroetorphine has micro opioid agonist activity there is evidence to suggest that it is not identical to that of morphine. This study compared dihydroetorphine to other opioids under behavioral conditions that are sensitive to micro opioid agonism. The acute effects of dihydroetorphine, etorphine and morphine were evaluated using two procedures. In one procedure, monkeys received 3.2 mg/kg per day of morphine and discriminated naltrexone from saline while responding under a fixed-ratio 5 schedule of stimulus shock termination. In addition, a warm-water, tail-withdrawal procedure was used in untreated monkeys. When acutely deprived of morphine, monkeys responded on the naltrexone lever, and this effect was reversed by dihydroetorphine, etorphine and morphine. Each agonist produced the maximum (20-s latency) antinociceptive effect in 50 degrees C water. Naltrexone antagonized the discriminative stimulus and antinociceptive effects of dihydroetorphine and etorphine, although Schild analyses yielded large variability in slopes and pA(2) values. Naltrexone reversed established effects of dihydroetorphine and morphine in both procedures and pretreatment with dihydroetorphine (2, 6 or 24 h) did not alter the discriminative stimulus effects of morphine. Taken together, these data support the notion that dihydroetorphine is a micro agonist with a short duration of action; however, variability in antagonism of dihydroetorphine and morphine might be a manifestation of differences that have been reported for these drugs at the cellular level.

  12. Antinociceptive Effect of Najanalgesin from Naja Naja Atra in a Neuropathic Pain Model via Inhibition of c-Jun NH2-terminal Kinase.

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    Liang, Ying-Xia; Zhang, Zhi-Yu; Zhang, Rui

    2015-09-05

    Najanalgesin, a toxin isolated from the venom of Naja naja atra, has been shown to exert significant analgesic effects in a neuropathic pain model in rats. However, the molecular mechanism underlying this protective effect of najanalgesin is poorly understood. The present study sought to evaluate the intracellular signaling pathways that are involved in the antinociceptive effect of najanalgesin on neuropathic pain. The antinociceptive properties of najanalgesin were tested in hind paw withdrawal thresholds in response to mechanical stimulation. We analyzed the participation of the mitogen-activated protein kinase p38, extracellular-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) by western blot analysis. This inhibition of JNK was confirmed by immunohistochemistry. The phosphorylation levels of JNK (as well as its downstream molecule c-Jun), p38, and ERK were significantly increased after injury. Najanalgesin only inhibited JNK and c-Jun phosphorylation but had no effect on either ERK or p38. This inhibition of JNK was confirmed by immunohistochemistry, which suggested that the antinociceptive effect of najanalgesin on spinal nerve ligation-induced neuropathic pain in rats is associated with JNK activation in the spinal cord. The antinociceptive effect of najanalgesin functions by inhibiting the JNK in a neuropathic pain model.

  13. 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.

  14. The Induction of Heme Oxygenase 1 Decreases Painful Diabetic Neuropathy and Enhances the Antinociceptive Effects of Morphine in Diabetic Mice

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    Castany, Sílvia; Carcolé, Mireia; Leánez, Sergi; Pol, Olga

    2016-01-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus which is poorly controlled by conventional analgesics. This study investigates if treatment with an heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the allodynia and hyperalgesia induced by diabetes and enhanced the antinociceptive effects of morphine. In a diabetic mice model induced by the injection of streptozotocin (STZ), we evaluated the antiallodynic and antihyperalgesic effects produced by the intraperitoneal administration of 5 and 10 mg/kg of CoPP at several days after its administration. The antinociceptive actions produced by the systemic administration of morphine alone or combined with CoPP were also evaluated. In addition, the effects of CoPP treatment on the expression of HO-1, the microglial activation marker (CD11b/c), the inducible nitric oxide synthase (NOS2) and μ-opioid receptors (MOR), were also assessed. Our results showed that the administration of 10 mg/kg of CoPP during 5 consecutive days completely blocked the mechanical and thermal hypersensitivity induced by diabetes. These effects are accompanied by the increased spinal cord, dorsal root ganglia and sciatic nerve protein levels of HO-1. In addition, the STZ-induced activation of microglia and overexpression of NOS2 in the spinal cord were inhibited by CoPP treatment. Furthermore, the antinociceptive effects of morphine were enhanced by CoPP treatment and reversed by the administration of an HO-1 inhibitor, tin protoporphyrin IX (SnPP). The spinal cord expression of MOR was also increased by CoPP treatment in diabetic mice. In conclusion, our data provide the first evidence that the induction of HO-1 attenuated STZ-induced painful diabetic neuropathy and enhanced the antinociceptive effects of morphine via inhibition of microglia activation and NOS2 overexpression as well as by increasing the spinal cord levels of MOR. This study proposes the administration of CoPP alone or

  15. Dose-related antinociceptive effects of intravenous buprenorphine in cats.

    Science.gov (United States)

    Steagall, Paulo V M; Mantovani, Fernanda B; Taylor, Polly M; Dixon, Mike J; Luna, Stelio P L

    2009-11-01

    The dose-related antinociceptive effects of intravenous (IV) buprenorphine were evaluated in cats. Thermal (TT) and mechanical threshold (MT) devices were used for nociceptive stimulation. After baseline threshold recordings, buprenorphine was administered IV (0.01, 0.02 or 0.04 mg/kg; B1, B2 and B4, respectively) in a randomised, blinded and cross-over study. Data were analysed by ANOVA (P<0.05) using 95% confidence intervals (CI). TT increased 15, 30, 45 min and 1 (5.2+/-2.7 degrees C), 2, 3 and 4 h after B1; 15, 30, 45 min and 1 (5.1+/-3.9 degrees C) and 2 h after B2, and 15, 30, 45 min and 1 (5.4+/-3.3 degrees C), 2, 3, 6 and 8 h after B4. MT increased 15 and 45 min after B2 (260+/-171 mmHg), and 30 (209+/-116 mmHg) and 45 min and 1 and 2 h after B4. At 45 min, MT values were significantly higher after B2 compared to B1 (P<0.05). With MT, B2 and B4 produced more antinociception and longer duration of action than B1, respectively. No dose response to thermal stimulation was detected.

  16. Antinociceptive effect of Hyptis pectinata leaves extracts.

    Science.gov (United States)

    Lisboa, Ana C C D; Mello, Iderjane C M; Nunes, Rogeria S; Dos Santos, Marquês A; Antoniolli, Angelo R; Marçal, Rosilene M; Cavalcanti, Sócrates C de H

    2006-09-01

    Oral administration of hexanes, chloroform, and ethyl acetate extracts of the leaves of Hyptis pectinata significantly reduced the number of writhing induced by acetic acid and increased the response to thermal stimuli in hot-plate test. Such effect was completely reversed by the opioid antagonist naloxone.

  17. Acupuncture manipulation enhances anti-nociceptive effect on formalin-induced pain in rats.

    Science.gov (United States)

    Kim, Gun Ho; Yeom, Mijung; Yin, Chang Shik; Lee, Hyejung; Shim, Insop; Hong, Mee Sook; Kim, Chang-Ju; Hahm, Dae-Hyun

    2010-02-01

    In order to apply appropriate acupuncture stimulation, different needle manipulation techniques are required. These manipulations are performed in many ways such as twirling the needle, varying the insertion angle, etc. The present study was designed to evaluate the antinociceptive effect of these manipulations to the acupuncture point ST36 on formalin-induced pain in rats. Animals were divided into four groups: non-treated control (CON), acupuncture without manipulation (AT), acupuncture with twirling manipulation (TM) and acupuncture with lifting-thrusting manipulation (LM) group. Level of pain was measured in formalin-injected rats in the early (0-10 minutes) and the late (10-60 minutes) phase. Several pain-related gene expressions were investigated in the spinal cord using reverse transcriptase-polymerase chain reaction analysis. Formalin-induced pain was significantly reduced in the TM and the LM groups, compared with the CON and the AT groups. TM was more effective than LM in both phases. Needle manipulation was also effective in suppressing the mRNA expression of pain-related genes such as Fos, opioid receptor-like 1, tachykinin 1, tachykinin receptor 1, mu-opioid receptor and 5-hydroxytryptamine receptor 2A in the spinal cord. The TM and the LM groups showed enhanced analgesia, compared with the AT group. This effect might be related to the suppression of the transcription of pain-related genes.

  18. Antinociceptive effect of ethanolic extract of Selaginella convoluta in mice

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    de Sá Pedro Guilherme S

    2012-10-01

    Full Text Available Abstract Background Selaginella convoluta (Arn. Spring (Selaginellaceae, commonly known as “jericó”, is a medicinal plant found in northeastern Brazil. S. convoluta is used in folk medicine as an antidepressant, aphrodisiac, diuretic, analgesic, anti-inflammatory and it is used to combat amenorrhea, coughing and bleeding. This study was performed to evaluate the antinociceptive effects of ethanolic extract from S. convoluta in mice exposed to chemical and thermal models of nociception. Methods Preliminary phytochemical analysis of the ethanolic extract was performed. The ethanolic extract from Selaginella convoluta (Sc-EtOH was examined for its intraperitoneal (i.p. antinociceptive activity at the doses of 100, 200 and 400 mg/kg body weight. Acetic acid-induced writhing, formalin injection and hot plate tests were used to evaluate the antinociceptive activity of Sc-EtOH extract. The rota-rod test was used to evaluate motor coordination. Results A preliminary analysis of Sc-EtOH revealed that it contained phenols, steroids, terpenoids and flavonoids. In the acetic acid-induced writhing test, mice treated with Sc-EtOH (100, 200 and 400 mg/kg, i.p. exhibited reduced writhing (58.46, 75.63 and 82.23%, respectively. Secondly, Sc-EtOH treatment (100, 200 and 400 mg/kg, i.p. decreased the paw licking time in mice during the first phase of the formalin test (by 44.90, 33.33 and 34.16%, respectively, as well as during the second phase of the test (by 86.44, 56.20 and 94.95%, respectively. Additionally, Sc-EtOH treatment at doses of 200 and 400 mg/kg increased the latency time in the hot plate test after 60 and 90 minutes, respectively. In addition, Sc-EtOH did not impair motor coordination. Conclusion Overall, these results indicate that Sc-EtOH is effective as an analgesic agent in various pain models. The activity of Sc-EtOH is most likely mediated via the inhibition of peripheral mediators and central inhibitory mechanisms. This study supports

  19. Antinociceptive effect of a novel tosylpyrazole compound in mice.

    Science.gov (United States)

    Oliveira, Sara M; Gewehr, Camila; Dalmolin, Gerusa D; Cechinel, Cleber A; Wentz, Alexandre; Lourega, Rogério V; Sehnem, Ronan C; Zanatta, Nilo; Martins, Marcos A P; Rubin, Maribel A; Bonacorso, Helio G; Ferreira, Juliano

    2009-02-01

    Pain is the most common complaint in the medical field and the identification of compounds that can effectively treat painful states without induction of side-effects remains a major challenge in biomedical research. The aim of the present study was to investigate the antinociceptive effect of a novel compound, 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (compound A) in several models of pain in mice and compare with those produced by the known trifluoromethyl-containing pyrazole compound celecoxib. Compound A or celecoxib were administrated by oral (78-780 micromol/kg), intrathecal (9-22.5 nmol/site) or intracerebroventricular (9-22.5 nmol/site) routes. Oral administration of either compound A or celecoxib abolished the mechanical allodynia, but not the oedema caused by intraplantar injection of carrageenan. Similarly, compound A reduced the overt nociception, but not the oedema, produced by bradykinin or capsaicin. However, compound A (500 micromol/kg, orally) did not alter nociception nor oedema caused by intraplantar injection of prostaglandin E(2 )or glutamate, whereas celecoxib reduced only the nociception induced by the former. Moreover, oral and intrathecal administration of compound A or celecoxib also reduced the nociception induced by acetic acid. However, only celecoxib reduced the acetic acid-induced nociception when it was injected by the intracerebroventricular route. Finally, neither compound A nor celecoxib was able to produce antinociceptive effect in the tail-flick test or to alter the motor performance and the body temperature. Besides, compound A or celecoxib did not induce gastric lesion. Thus, compound A seems to be an interesting prototype for the development of novel analgesic drugs.

  20. Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats.

    Science.gov (United States)

    Jain, N K; Kulkarni, S K

    1999-12-15

    Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.

  1. The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms.

    Science.gov (United States)

    Schreiber, Shaul; Rigai, Tova; Katz, Yeshayahu; Pick, Chaim G

    2002-09-30

    The antinociceptive effects of the noradrenergic and specific serotonergic antidepressant (NaSSA) drug mirtazapine and its interaction with various opioid receptor subtypes were evaluated in mice with a hotplate analgesicmeter. Mirtazapine elicited an antinociceptive effect in a dose-dependent manner following doses from 1 to 7.5mg/kg. As the mirtazapine dose increased beyond 10mg/kg latencies returned to baseline, yielding a biphasic dose-response curve. The effect of opioid, adrenergic, and serotonergic receptor antagonists was examined as to their ability to block mirtazapine antinociception. Mirtazapine (at 10mg/kg)-induced antinociception was significantly inhibited by naloxone, nor-BNI, and naltrindole, but neither by beta-FNA nor by naloxonazine, implying the involvement of kappa(1)- and delta-opioid mechanisms. When adrenergic and serotonergic antagonists were used, both metergoline and yohimbine, decreased antinociception elicited by mirtazapine, implying a combined serotonergic and noradrenergic mechanism of antinociception. When mirtazapine was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated only by kappa(3)-opioid receptor subtypes. Summing up these results we conclude that the antinociceptive effect of mirtazapine is mainly influenced by the kappa(3)-opioid receptor subtype combined with both serotonergic and noradrenergic receptors. These results suggest a potential use of mirtazapine in the management of some pain syndromes, and raise questions regarding a possible indirect opioid-dependence induced by mirtazapine. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mirtazapine when prescribed for pain.

  2. Antinociceptive and Toxicological Effects of Dioclea grandiflora Seed Pod in Mice

    Science.gov (United States)

    Sá, Rita de Cássia da Silveira e; de Oliveira, Leandra Eugênia Gomes; de Farias Nóbrega, Franklin Ferreira; Bhattacharyya, Jnanabrata; de Almeida, Reinaldo Nóbrega

    2010-01-01

    The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice. PMID:20368784

  3. 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

  4. Antinociceptive effect of methanol extract of leaves of Persicaria hydropiper in mice.

    Science.gov (United States)

    Khatun, Ambia; Imam, Mohammad Zafar; Rana, Md Sohel

    2015-03-13

    Persicaria hydropiper (Linn.) Delarbre is a common plant of Polygonaceae family commonly called Bishkatali in Bangladesh. Leaves of the plant are traditionally used in the treatment of rheumatic pain, gout, and skin diseases such as ringworms, scabies, boils, abscesses, carbuncles, bites of snakes, dogs or insects. This study evaluated the antinociceptive effect of the methanol extract of P. hydropiper leaves (MEPH). The antinociceptive activity of MEPH was investigated using heat-induced (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 25, 50, and 75 mg/kg doses. Involvement of opioid system, cyclic guanosine monophosphate (cGMP) pathway, and ATP-sensitive K(+) channel pathway were also tested using naloxone, methylene blue and glibenclamide respectively. MEPH showed antinociceptive activity in both heat- and chemical induced pain models. In both hot plate and tail immersion tests MEPH significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract inhibited the number of abdominal writhing. Likewise, MEPH produced significant dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplantar injection of formalin. Besides, MEPH also significantly inhibited the glutamate-induced pain and cinnamaldehyde-induced pain in mice. It was also clear that pretreatment with naloxone significantly reversed the antinociception produced by MEPH in hot plate and tail immersion test suggesting the involvement of opioid system in its effect. In addition, administration of methylene blue, a non specific inhibitor of NO/guanylyl cyclase, enhanced MEPH induced antinociception while glibenclamide, an ATP-sensitive K(+) channel antagonist, could not reverse antinociceptive activity induced by MEPH. Based on the results of the current study it can be said that MEPH possesses significant antinociceptive activity

  5. 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.

  6. 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.

  7. Anti-nociceptive effect of Agrimonia eupatoria extract on a ...

    African Journals Online (AJOL)

    Background: Natural products including Agrimonia eupatoria are considered an incomparable source of molecular diversity that has led to the medicines, especially for pain treatment. To investigate the antinociception of Agrimonia eupatoria, we examined its activity in a rat model of cisplatin neuropathy. Materials and ...

  8. Antinociceptive and Anti-Inflammatory Effects of Solvent Extracts of ...

    African Journals Online (AJOL)

    Erah

    SGRS College of Pharmacy, Department of Pharmacology, Pune University, Saswad, Tal-Purandar, Pune 412301,. India ... the plant material. Keywords: Tagetes erectus, Antinociceptive, Anti-inflammatory. Received: 30 December 2008. Revised accepted: 18 May 2009 ... solvent extracts of the leaves of this plant for.

  9. 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% ...

  10. Antinociceptive and Anti-Inflammatory Effects of Solvent Extracts of ...

    African Journals Online (AJOL)

    (phenylbutazone). It also increased pain threshold in the oedematous right hind limb paw of the rats. Conclusion: The results obtained show that the extracts of Tagetes erectus L. (Asteraceae) has antinociceptive and anti-inflammatory properties. This finding provides a basis for the traditional use of the plant material.

  11. Dissociation of rewarding, anti-aversive and anti-nociceptive effects of different classes of anti-nociceptives in the rat.

    Science.gov (United States)

    Rutten, Kris; De Vry, Jean; Robens, Angela; Tzschentke, Thomas M; van der Kam, Elizabeth L

    2011-03-01

    It was previously shown that morphine more potently reduces the affective as compared to the sensory component of nociception, and this effect is independent of morphine's rewarding properties. Here we investigated whether this finding can be generalized to other classes of anti-nociceptive drugs. The effect of oxycodone (0-10 mg/kg, i.p.), tramadol (0-10 mg/kg, i.p.), ibuprofen (0-300 mg/kg, i.p.) and pregabalin (0-31.6 mg/kg, i.p.) on negative affect and mechanical hypersensitivity accompanying carrageenan-induced (0.5% intraplantar) inflammatory nociception was assessed using conditioned place aversion (CPA) and Randall Selitto paw pressure test, respectively. The rewarding effect of these drugs was assessed using conditioned place preference (CPP). All four anti-nociceptive drugs dose-dependently reduced carrageenan-induced CPA and mechanical hypersensitivity. Furthermore all drugs induced CPP, except for ibuprofen. Similar to morphine, oxycodone and tramadol showed a large dissociation of anti-aversive versus anti-nociceptive potency, i.e. 10 times more potent against the affective versus the sensory component of nociception. Oxycodone and tramadol were 30 and 10 times more potent to produce CPP in animals under normal versus painful conditions. Ibuprofen and pregabalin also showed a dissociation of anti-aversive and anti-nociceptive potency, but less pronounced (i.e. three times more potent against the affective component). However, pregabalin showed no dissociation between rewarding potency under normal versus painful conditions. Taken together, these data suggest that the dissociation of rewarding potency in animals under normal versus painful conditions is limited to drugs with an opioid mechanism of action, while the dissociation of anti-aversive and anti-nociceptive potency applies to anti-nociceptive drugs with different mechanisms of action. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by

  12. Opposite effects of neuropeptide FF on central antinociception induced by endomorphin-1 and endomorphin-2 in mice.

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    Zi-long Wang

    Full Text Available Neuropeptide FF (NPFF is known to be an endogenous opioid-modulating peptide. Nevertheless, very few researches focused on the interaction between NPFF and endogenous opioid peptides. In the present study, we have investigated the effects of NPFF system on the supraspinal antinociceptive effects induced by the endogenous µ-opioid receptor agonists, endomorphin-1 (EM-1 and endomorphin-2 (EM-2. In the mouse tail-flick assay, intracerebroventricular injection of EM-1 induced antinociception via µ-opioid receptor while the antinociception of intracerebroventricular injected EM-2 was mediated by both µ- and κ-opioid receptors. In addition, central administration of NPFF significantly reduced EM-1-induced central antinociception, but enhanced EM-2-induced central antinociception. The results using the selective NPFF1 and NPFF2 receptor agonists indicated that the EM-1-modulating action of NPFF was mainly mediated by NPFF2 receptor, while NPFF potentiated EM-2-induecd antinociception via both NPFF1 and NPFF2 receptors. To further investigate the roles of µ- and κ-opioid systems in the opposite effects of NPFF on central antinociception of endomprphins, the µ- and κ-opioid receptors selective agonists DAMGO and U69593, respectively, were used. Our results showed that NPFF could reduce the central antinociception of DAMGO via NPFF2 receptor and enhance the central antinociception of U69593 via both NPFF1 and NPFF2 receptors. Taken together, our data demonstrate that NPFF exerts opposite effects on central antinociception of endomorphins and provide the first evidence that NPFF potentiate antinociception of EM-2, which might result from the interaction between NPFF and κ-opioid systems.

  13. 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

  14. Antinociceptive Effect of Some Biuret Derivatives on Formalin Test in Mice

    OpenAIRE

    Adibpour, Neda; Poornajjari, Ali; Khodayar, Mohammad Javad; Rezaee, Saeed

    2013-01-01

    Purpose: The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N`-diphenyl, N-phenyl-N`-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-yl)thio substituents on the formalin-evoked pain in mice. Methods: Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomet...

  15. Antinociceptive effect and acute toxicity of the Hyptis suaveolens leaves aqueous extract on mice.

    Science.gov (United States)

    Santos, Thiago C; Marques, Maxsuel S; Menezes, Igor A C; Dias, Kellyane S; Silva, Aline B L; Mello, Iderjane C M; Carvalho, Ana C S; Cavalcanti, Sócrates C H; Antoniolli, Angelo R; Marçal, Rosilene M

    2007-07-01

    The aqueous extract of Hyptis suaveolens leaves was studied for their antinociceptive property in chemical and thermal models of nociception in mice. Oral administration of the aqueous extract (100, 200, and 400 mg/kg) dose-dependently reduced the number of writhings induced by acetic acid, decreased the licking activity of the early phase in formalin test and increased the reaction time in hot-plate test. The antinociceptive effect was significantly antagonized by naloxone (3 mg/kg; i.p.). Preliminary acute toxicity study showed that no animal death with doses up to 5 g/kg (p.o.).

  16. 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.

  17. Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice.

    Science.gov (United States)

    Eidi, Akram; Moghadam-kia, Sara; Moghadam, Jalal Zarringhalam; Eidi, Maryam; Rezazadeh, Shamsali

    2012-03-01

    Olive [Olea europaea L. (Oleaceae)] is a long-lived evergreen tree that is widespread in different parts of the world. Olive oil has been reported to relieve pain; however, there is still insufficient data in the literature on the subject. Thus, it is considered worthwhile investigating the antinociceptive and anti-inflammatory effects of olive oil in adult male Balb/C mice. The antinociceptive effects were studied using formalin, hot plate and writhing tests. The acute anti-inflammatory effects of olive oil in mice were studied using xylene ear edema test. Olive oil (1, 5 and 10 ml/kg body wt.) was injected intraperitoneally. Intact animals served as controls. Our results showed that the olive oil only decreased the second phase of formalin-induced pain. In the hot plate test, olive oil did not raise the pain threshold over the 60 min duration of the test. Olive oil exhibited antinociceptive activity against writhing-induced pain by acetic acid. In the xylene ear edema test, olive oil showed significant anti-inflammatory activity in the mice. The present data indicated that olive oil has antinociceptive and anti-inflammatory effects in mice but further investigation of these effects is required to elucidate the mechanism(s) involved in analgesic and anti-inflammatory effects of Olea europaea oil.

  18. Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

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    Wilson Alves Ferreira Junior

    2017-12-01

    Full Text Available Bunodosine 391 (BDS 391, a low molecular weight compound isolated from the sea anemone Bunodosoma cangicum, increases the nociceptive threshold and inhibits inflammatory hyperalgesia. Serotonin receptors are involved in those effects. In this study, we have expanded the characterization of the antinociceptive effect of BDS 391 demonstrating that, in rats: (a the compound inhibits (1.2–12 ng/paw overt pain, in the formalin test, and mechanical hyperalgesia (0.6–6.0 ng/paw detected in a model of neuropathic pain; (b intraplantar administration of ondansetron, a selective 5-HT3 receptor antagonist, blocks the effect of BDS 391, whereas ketanserin, a 5-HT2 receptor antagonist, partially reversed this effect, indicating the involvement of peripheral 5-HT2 and 5-HT3 receptors in BDS 391 antinociception; and (c in binding assay studies, BDS 391 was not able to displace the selective 5-HT receptor antagonists, suggesting that this compound does not directly bind to these receptors. The effect of biguanide, a selective 5-HT3 receptor agonist, was also evaluated. The agonist inhibited the formalin’s nociceptive response, supporting an antinociceptive role for 5-HT3 receptors. Our study is the first one to show that a non-peptidic low molecular weight compound obtained from a sea anemone is able to induce antinociception and that activation of peripheral 5-HT3 receptors contributes to this effect.

  19. Dry needle stimulation of myofascial trigger points evokes segmental anti-nociceptive effects.

    Science.gov (United States)

    Srbely, John Z; Dickey, James P; Lee, David; Lowerison, Mark

    2010-05-01

    To test the hypothesis that dry needle stimulation of a myofascial trigger point (sensitive locus) evokes segmental anti-nociceptive effects. Double-blind randomized controlled trial. Forty subjects (21 males, 19 females). Test subjects received intramuscular dry needle puncture to a right supraspinatus trigger point (C4,5); controls received sham intramuscular dry needle puncture. Pain pressure threshold (PPT) readings were recorded from right infraspinatus (C5,6) and right gluteus medius (L4,5S1) trigger points at 0 (pre-needling baseline), 1, 3, 5, 10 and 15 min post-needling and normalized to baseline values. The supraspinatus and infraspinatus trigger points are neurologically linked at C5; the supraspinatus and gluteus medius are segmentally unrelated. The difference between the infraspinatus and gluteus medius PPT values (PPTseg) represents a direct measure of the segmental anti-nociceptive effects acting at the infraspinatus trigger point. Significant increases in PPTseg were observed in test subjects at 3 (p = 0.002) and 5 (p = 0.015) min post-needling, compared with controls. One intervention of dry needle stimulation to a single trigger point (sensitive locus) evokes short-term segmental anti-nociceptive effects. These results suggest that trigger point (sensitive locus) stimulation may evoke anti-nociceptive effects by modulating segmental mechanisms, which may be an important consideration in the management of myofascial pain.

  20. 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.

  1. Antinociceptive Effect of Some Biuret Derivatives on Formalin Test in Mice

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    Neda Adibpour

    2014-03-01

    Full Text Available Purpose: The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N`-diphenyl, N-phenyl-N`-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-ylthio substituents on the formalin-evoked pain in mice. Methods: Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomethacin(20 mg/kg and vehicle of the compounds. Area under the pain score curve against time (AUEC up to 60 minutes was used as the measure of pain behavior. Results: A rather good analgesic effect was seen for most of the tested biuret derivatives. Significant reduction in median AUEC0-5 minutes was observed at the doses of 50 and 25 mg/kg for biurets with either benzyl and 2-methylquinoline-4-yl (C8 or phenylethyl and benzo[d]thiazol-2-ylthio(C9 moieties, respectively(p-value<0.0044. Antinociceptive activities of compound C7 (with bis phenylropyl substituent, C8 and C9 during the late phase of formaldehyde-induced pain were comparable to that of indomethacin. Conclusion: Unlike indomethacin, the tested biuret compounds are able to induce antinociception in both phases of formalin test and could be considered comparable to indomethacin at the selected doses.

  2. The intrathecal administration of losartan, an AT1 receptor antagonist, produces an antinociceptive effect through the inhibiton of p38 MAPK phosphorylation in the mouse formalin test.

    Science.gov (United States)

    Nemoto, Wataru; Ogata, Yoshiki; Nakagawasai, Osamu; Yaoita, Fukie; Tanado, Takeshi; Tan-No, Koichi

    2015-01-12

    We have recently reported that an intrathecal (i.t.) administration of angiotensin II (Ang II) into mice induces a nociceptive behavior accompanied by the activation of p38 MAPK signaling via AT1 receptors (Nemoto et al., 2013, Mol. Pain 9, 38). These results suggested that Ang II participates in the facilitation of nociceptive transmission in the spinal cord. In the present study, we used formalin test to examine the effect of i.t.-administered losartan, an AT1 receptor antagonist, and determine whether Ang II acts as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information. When administered i.t. 5 min before the injection of a 2% formalin solution into the plantar surface of the hindpaw, losartan (30-100 nmol) produced a dose-dependent and significant antinociceptive effect during both the first and second phases of the test. In the superficial dorsal horn of the spinal cord (laminae I and II), the fluorescence intensities for Ang II and phospho-p38 MAPK were both significantly increased on the ipsilateral side 3 min after the injection of formalin compared to saline-treated controls. Moreover, the increase of phospho-p38 MAPK fluorescence intensity was significantly inhibited by the i.t. administration of losartan (54.8 nmol) 5 min prior to formalin. These results indicate that losartan produces an antinociceptive effect through the inhibition of p38 MAPK phosphorylation in the mouse formalin test and that Ang II may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. 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.

  4. Nalbuphine could decrease the rewarding effect induced by tramadol in mice while enhancing its antinociceptive activity.

    Science.gov (United States)

    Abdel-Ghany, Rasha; Nabil, Mahmoud; Abdel-Aal, Mohamed; Barakat, Waleed

    2015-07-05

    Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been used as an analgesic or an adjuvant with morphine to attenuate the development of morphine dependence and rewarding effect. In this study, we investigated the effect of nalbuphine on tramadol rewarding effect and antinociception. Using the conditioned place preference (CPP) paradigm in mice, we demonstrated that co-administration of nalbuphine (7mg/kg, s.c.) with tramadol (70mg/kg, s.c.) during conditioning completely blocked the CPP induced by tramadol. Co-administration of nalbuphine blocked the increase in dopamine level in the nucleus accumbens induced by tramadol. These actions were accompanied by an increase rather than attenuation of the antinociceptive effect of tramadol. These results suggest that nalbuphine could have a great potential as a pharmacotherapy for tramadol abuse. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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.

  7. Evaluation of antinociceptive effect of Petiveria alliacea (Guiné) in animals.

    Science.gov (United States)

    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.

  8. Antinociceptive and anti-inflammatory effects of aqueous extract of Chenopodium opulifolium schrad leaves

    Science.gov (United States)

    Ajayi, Abayomi M.; Tanayen, Julius Khidzee; Magomere, Albert; Ezeonwumelu, Joseph O. C.

    2017-01-01

    Aim: Chenopodium opulifolium is a specie of the Chenopodiaceae commonly used as vegetables in local diet and for treating different ailment in Uganda. This study was conducted to evaluate the antioxidant, antinociceptive and anti-inflammatory effects of the aqueous extract of C. opulifolium leaves (AECO). Materials and Methods: The dried leaf of the plant was extracted by maceration in water. Qualitative and quantitative phytochemical analysis, antioxidants, and membrane stabilizing effects were determined in the extract. The extract was then investigated for acute toxicity, antinociceptive (writhing, hot plate and open field test), and anti-inflammatory (egg albumin-induced paw edema) effects in rodents. Results: Phytochemical analysis revealed the presence of alkaloids, tannins, phlobatannins, flavonoids, and saponins in AECO. Total caffeic acid derivatives and total flavonoids content were 91.7 mgCAE/g sample and 94.7 mgRE/g sample, respectively. AECO demonstrated antioxidant effects in both 1,1-diphenyl-2-picryl-hydrazyl and NO assays. Significant membrane stabilizing activity was observed in both the heat and hypotonic solution-induced lysis of erythrocytes. The acute toxicity test showed that AECO (5000 mg/kg) did not cause any significant change in behavior or death in rats. AECO (100-400 mg/kg) produced a significant antinociceptive effect in both the writhing and hot plate tests, but no significant reduction in the locomotory activity in mice. Furthermore, the extract significantly (P egg albumin-induced rat paw edema by 44.2%, 44.5%, and 51.2%, respectively, after 120 min. Conclusion: The results showed that C. opulifolium extract possesses significant antioxidant, antinociceptive and anti-inflammatory effects, and these affirm the reasons for its folkloric use. PMID:28163955

  9. Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.

    Science.gov (United States)

    Martin, Loren J; Piltonen, Marjo H; Gauthier, Josee; Convertino, Marino; Acland, Erinn L; Dokholyan, Nikolay V; Mogil, Jeffrey S; Diatchenko, Luda; Maixner, William

    2015-12-01

    Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 β-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible β-AR intrinsic agonist activity and displayed a full competitive antagonist profile at β(1)/β(2)/β(3)-ARs, producing a unique blockade of β(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible β-AR intrinsic agonist activity and unique blockade of β(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions. The S enantiomer of bupranolol, a β-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique β-adrenergic receptor compound to advance future clinical pain studies. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Antinociceptive Effect of Hydroalcoholic Leaf Extract of Hedera helix in Male Rat

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    S. Shahidi

    2013-07-01

    Full Text Available Introduction & Objective: The consumption of chemical compounds and medicinal herbs are different ways to control pain. On the other hand, the complications of chemical drugs and their expensiveness cause people to use herbal medicines The aim of this study was to inves-tigate the antinociceptive effect of hydroalcoholic leaf extract of Hedera helix in male rats. Materials & Methods: In this experimental study, 36 adult male rats were divided into 6 groups: control, morphine (1mg/kg, Hedera helix extract (100, 200, 300mg/kg, i.p. and naloxone (1mg/kg with Hedera helix extract (200 mg/kg. The analgesic effects of Hedera helix ex-tract were assessed with writhing and tail flick tests. Results: The results of this study showed that doses of 200 and 300mg/kg of Hedera helix ex-tract decreased pain significantly. However, dose of 300mg/kg of Hedera helix extract showed more antinociceptive effect of Hedera helix extract. The naloxone and Hedera helix extract combination increased the number of writhing compared with the Hedera helix ex-tract group. Conclusion: In this study analgesic effect of the hydroalcoholic extract of Hedera helix was observed. The antinociceptive effect of extract was probably occurred by activation of opioid system. (Sci J Hamadan Univ Med Sci 2013; 20 (2:119-125

  11. 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

    . 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...... 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 (P... as with subcutaneous administration, and had a later onset. It is advised to administer the oral formulation of buprenorphine in Nutella® in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration....

  12. Antinociceptive Activity of Trichilia catigua Hydroalcoholic Extract: New Evidence on Its Dopaminergic Effects

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    Alice F. Viana

    2011-01-01

    Full Text Available Trichilia catigua is a native plant of Brazil; its barks are used by some local pharmaceutical companies to prepare tonic drinks, such as Catuama. The present study was addressed to evaluate the effects of T. catigua hydroalcoholic extract in mouse nociception behavioral models, and to evaluate the possible mechanisms involved in its actions. Male Swiss mice were submitted to hot-plate, writhing and von Frey tests, after oral treatment with T. catigua extract (200 mg kg−1, p.o.. The extract displayed antinociceptive effect in all three models. For characterization of the mechanisms involved in the antinociceptive action of the extract, the following pharmacological treatments were done: naloxone (2.5 mg kg−1, s.c., SR141716A (10 mg kg−1, i.p., SCH23390 (15 μg kg−1, i.p., sulpiride (50 mg kg−1, i.p., prazosin (1 mg kg−1, i.p., bicuculline (1 mg kg−1, i.p. or dl-p-chlorophenylalanine methyl ester (PCPA, 100 mg kg−1, i.p.. In these experiments, the action of T. catigua extract was evaluated in the hot-plate test. The treatment with SCH23390 completely prevented the antinociceptive effect, while naloxone partially prevented it. The possible involvement of the dopaminergic system in the actions of T. catigua extract was substantiated by data showing the potentiation of apomorphine-induced hypothermia and by the prevention of haloperidol-induced catalepsy. In conclusion, the antinociceptive effects of T. catigua extract seem to be mainly associated with the activation of dopaminergic system and, to a lesser extent, through interaction with opioid pathway.

  13. 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

  14. Antinociceptive effect of Encholirium spectabile: A Bromeliaceae from the Brazilian caatinga biome

    Science.gov (United States)

    de Lima-Saraiva, Sarah Raquel Gomes; Silva, Juliane Cabral; Branco, Carla Rodrigues Cardoso; Branco, Alexsandro; Cavalcanti Amorim, Elba Lúcia; da Silva Almeida, Jackson Roberto Guedes

    2014-01-01

    Background: Encholirium spectabile is a species found in outcrops rocky throughout the Brazilian Caatinga. Objective: This study was carried out to evaluate the antinociceptive effects of ethanolic extract of the leaves from E. spectabile (Es-EtOH) in mice using chemical and thermal models of nociception. Material and Methods: HPLC was used to determine the fingerprint chromatogram. The Es-EtOH was examined for its antinociceptive activity at the doses of 100, 200 and 400 mg/kg intraperitoneal (i.p.). The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests in mice. Rota-rod test was used for the evaluation of motor coordination. Results: In the acetic acid-induced writhing test, the Es-EtOH (100, 200 and 400 mg/kg, i.p.) reduced the number of writhings by 68.59, 79.33 and 65.28%, respectively. Additionally, Es-EtOH (100, 200 and 400 mg/kg, i.p.) decreased by 34.14, 52.61 and 60.97% the paw licking time in the first phase, as well as 89.56, 79.90 and 96.71% in the second phase of the formalin test, respectively. Es-EtOH also showed effect in the hot plate test, since increased the latency time at dose of 100 mg/kg after 60 minutes. In addition, Es-EtOH did not impair motor coordination. The presence of phenolic compounds in the extract was confirmed using HPLC. These results indicate that Es-EtOH has antinociceptive activity, probably of peripheral origin. The mechanism involved is not completely understood but, at least in part there is the participation of opioid receptors. PMID:25298687

  15. Antinociceptive effect of some biuret derivatives on formalin test in mice.

    Science.gov (United States)

    Adibpour, Neda; Poornajjari, Ali; Khodayar, Mohammad Javad; Rezaee, Saeed

    2014-01-01

    The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N`-diphenyl, N-phenyl-N`-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-yl)thio substituents on the formalin-evoked pain in mice. Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomethacin(20 mg/kg) and vehicle of the compounds. Area under the pain score curve against time (AUEC) up to 60 minutes was used as the measure of pain behavior. A rather good analgesic effect was seen for most of the tested biuret derivatives. Significant reduction in median AUEC0-5 minutes was observed at the doses of 50 and 25 mg/kg for biurets with either benzyl and 2-methylquinoline-4-yl (C8) or phenylethyl and benzo[d]thiazol-2-ylthio(C9) moieties, respectively(p-valuetested biuret compounds are able to induce antinociception in both phases of formalin test and could be considered comparable to indomethacin at the selected doses.

  16. Orofacial antinociceptive effect of the ethanolic extract of Annona vepretorum Mart. (Annonaceae).

    Science.gov (United States)

    Silva, Juliane C; Macedo, Larissa A R O; Souza, Grasielly R; Oliveira-Junior, Raimundo G; Lima-Saraiva, Sarah R G; Lavor, Érica M; Silva, Mariana G; Souza, Marilia T S; Bonjardim, Leonardo R; Quintans-Júnior, Lucindo J; Mendes, Rosemairy L; Almeida, Jackson R G S

    Annona vepretorum Mart. (Annonaceae) is a species popularly known in Brazil as "araticum" and "pinha da Caatinga". We have evaluated the antinociceptive effects of A. vepretorum in formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male Swiss mice were pretreated with either saline (p.o.), A. vepretorum ethanol extract (Av-EtOH 25, 50 and 100 mg/kg, p.o.), or morphine (10 mg/kg, i.p.), before formalin, capsaicin, or glutamate was injected into the right upper lip. Pre-treatment with Av-EtOH at all doses produced a reduction in face-rubbing behavior induced by formalin in both phases, and these pre-treatments also produced a significant antinociceptive effect in the capsaicin and glutamate tests. Pre-treatment with naloxone (1.5 mg/kg, i.p.) did not reverse the antinociceptive activity of the extract at the dose of 100 mg/kg in the first phase of this test. Our results suggest that Av-EtOH might be useful in the treatment of orofacial pain.

  17. Suppression of adrenal gland-derived epinephrine enhances the corticosterone-induced antinociceptive effect in the mouse formalin test.

    Science.gov (United States)

    Kang, S Y; Roh, D H; Kim, H W; Han, H J; Beitz, A J; Lee, J H

    2014-05-01

    There is both clinical and experimental evidence to support the application of corticosterone in the management of inflammation and pain. Corticosterone has been used to treat painful inflammatory diseases and can produce antinociceptive effects. Epinephrine is synthesized from norepinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and works as an endogenous adrenoceptor ligand secreted peripherally by the adrenal medulla. It is currently unclear whether corticosterone's antinociceptive effect is associated with the modulation of peripheral epinephrine. We first determined whether exogenous corticosterone treatment actually produced an antinociceptive effect in a formalin-induced pain model, and then examined whether this corticosterone-induced antinociceptive effect was altered by suppression of adrenal-derived epinephrine, using the following three suppression methods: (1) inhibition of the PNMT enzyme; (2) blocking peripheral epinephrine receptors; and (3) adrenalectomy. Exogenous treatment with corticosterone at a high dose (50 mg/kg), but not at lower doses (5, 25 mg/kg), significantly reduced pain responses in the late phase. Moreover, injection of 2,3-dichloro-a-methylbenzylamine, a PNMT enzyme inhibitor, (10 mg/kg) before corticosterone treatment caused a leftward shift in the dose-response curve for corticosterone and injection of propranolol (5 mg/kg), but not phentolamine, also shifted the dose-response curve to the left during the late phase. Chemical sympathectomy with 6-hydroxydopamine had no effect on corticosterone-induced antinociceptive effect, but injection of a low dose of corticosterone produced an antinociceptive effect in adrenalectomized animals. These results demonstrate that suppression of epinephrine, derived from adrenal gland, enhances the antinociceptive effect of exogenous corticosterone treatment in an inflammatory pain model. © 2013 European Pain Federation - EFIC®

  18. Orofacial antinociceptive effect and antioxidant properties of the hydroethanol extract of Hyptis fruticosa salmz ex Benth.

    Science.gov (United States)

    de Lima, Amanda C B; Paixão, Monica S; Melo, Mônica; de Santana, Marilia T; Damascena, Nicole P; Dias, Antonio S; Porto, Yasmin C B S; Fernandes, Ximene A; Santos, Clisiane C S; Lima, Clésio A; Quintans Júnior, Lucindo J; dos S Estevam, Charles; Araújo, Brancilene S

    2013-03-07

    Hyptis fruticosa is a plant native to Brazil with antinociceptive and antiinflamatory properties. This study evaluated the antinociceptive activity of the hydroethanol extract of the plant leaves (CHEE) against orofacial pain as well as its in vitro effect against lipid peroxidation. The antinociceptive activity was investigated in mice orally treated with different doses of the CHEE (50, 100, and 200 mg/kg) and morphine (5 mg/kg) using formalin, glutamate, and capsaicin orofacial pain models using. Lipoperoxidation was induced in egg yolk by AAPH and FeSO4 in the absence and presence of the CHEE (5, 50, 100, and 150 μg/mL). CHEE (200 mg/kg) significantly reduced (ρHyptis fruticosa leaf CHEE is of pharmacological interest because it was able to inhibit the peripheral and central transmission of orofacial pain, while reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. 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.

  20. The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice.

    Science.gov (United States)

    Castany, Sílvia; Carcolé, Mireia; Leánez, Sergi; Pol, Olga

    2016-06-01

    The activation of cannabinoid 2 receptors (CB2R) attenuates chronic pain, but the role played by carbon monoxide synthesized by the inducible heme oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R agonist, JWH-015, during painful diabetic neuropathy remains unknown. In streptozotocin (STZ)-induced diabetic mice, the anti-allodynic and anti-hyperalgesic effects of the subcutaneous administration of JWH-015 alone or combined with the intraperitoneal administration of a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer (CORM-2)) or an HO-1 inducer compound (cobalt protoporphyrin IX (CoPP)) at 10 mg/kg were evaluated. Reversion of JWH-015 anti-nociceptive effects by the administration of an HO-1 inhibitor (tin protoporphyrin IX (SnPP)) and a CB2R antagonist (AM630) was also evaluated. Furthermore, the protein levels of HO-1, neuronal nitric oxide synthase (NOS1), and CB2R in diabetic mice treated with CORM-2 and CoPP alone or combined with JWH-015 were also assessed. The administration of JWH-015 dose dependently inhibited hypersensitivity induced by diabetes. The effects of JWH-015 were enhanced by their coadministration with CORM-2 or CoPP and reversed by SnPP or AM630. The increased protein levels of HO-1 induced by CORM-2 and CoPP treatments were further enhanced in JWH-015-treated mice. All treatments similarly enhanced the peripheral expression of CB2R and avoided the spinal cord over-expression of NOS1 induced by diabetes. The activation of HO-1 enhanced the anti-nociceptive effects of JWH-015 in diabetic mice, suggesting that coadministration of JWH-015 with CORM-2 or CoPP might be an interesting approach for the treatment of painful diabetic neuropathy in mice.

  1. 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.

  2. Libidibia ferrea mature seeds promote antinociceptive effect by peripheral and central pathway: possible involvement of opioid and cholinergic receptors.

    Science.gov (United States)

    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.

  3. Antinociceptive Effect of the Essential Oil Obtained from the Leaves of Croton cordiifolius Baill. (Euphorbiaceae in Mice

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    Lenise de Morais Nogueira

    2015-01-01

    Full Text Available Croton cordiifolius Baill. is a shrub known as “quebra-faca” and is used to treat inflammation, pain, wounds, and gastrointestinal disturbances in the semiarid region in the northeast of Brazil. In an ethnobotanical survey in the state of Pernambuco, “quebra-faca” use was cited in 33% of the interviews. Thus, we decided to evaluate the antinociceptive effects of the essential oil from C. cordiifolius (CcEO. Chemical analysis by gas chromatography-mass spectrometry revealed 1,8-cineole (25.09% and α-phellandrene (15.43% as major constituents. Antinociceptive activity was evaluated using murine models of chemically induced pain (writhing induced by acetic acid, formalin, capsaicin, and glutamate tests. Opioid and central nervous systems (CNS involvement were also investigated. Regarding antinociceptive activity, CcEO (50 and 100 mg/kg reduced the number of writhing responses induced by acetic acid and decreased the licking times in both phases of the formalin test. CcEO also was evaluated in capsaicin- and glutamate-induced nociception. While no effect was observed in the capsaicin test, CcEO (100 mg/kg was effective in the glutamate test. Naloxone, an opioid antagonist, did not affect the antinociceptive activity of CcEO in writhing test. In conclusion, the antinociceptive effect of CcEO could be explained, at least in part, by inhibition of the glutamatergic system.

  4. Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

    Science.gov (United States)

    Bagüés, Ana; Martín, M Isabel; Sánchez-Robles, Eva M

    2014-12-15

    Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail. Muscle pain is a major clinical problem and new pharmacological approaches are being studied. Recently, we have demonstrated that cannabinoid synthetic agonists are useful to reduce muscular pain in two animal models, where the local administration is effective. Now, we want to know if tetrahydrocannabinol (THC), a cannabinoid natural derivative with therapeutic use in humans, is also effective in reducing acute muscle pain. The antinociceptive effect of THC by systemic (i.p.) and local (i.m.) administration was tested in two animal models of acute muscle pain, rat masseter and gastrocnemius, induced by hypertonic saline (HS) injection. The drugs used were the non-selective agonist THC and two selective cannabinoid antagonists, AM251 (CB1) and AM630 (CB2). THC, i.p. and i.m. administered, reduced the nociceptive behaviours induced by HS in both muscular pain models. The antinociceptive effect induced by the systemic administration of THC was mediated by CB1 receptors in the masseter muscle whereas in gastrocnemius both CB1 and CB2 receptors participated. When THC was administered locally, only CB2 receptors were involved in the antinociceptive effect in both muscles. This study suggests that THC could be a future pharmacological option in the treatment of muscle pain. The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice.

    Science.gov (United States)

    da Silva Brum, Evelyne; da Rosa Moreira, Laís; da Silva, Andreia Regina Haas; Boligon, Aline Augusti; Carvalho, Fabiano Barbosa; Athayde, Margareth Linde; Brandão, Ricardo; Oliveira, Sara Marchesan

    2016-09-15

    Tabernaemontana catharinensis (Apocynaceae) is a medicinal plant used for the treatment of painful and inflammatory disorders. Here, we investigated the antinociceptive potential of the ethyl acetate fraction (Eta) from T. catharinensis leaves and assessed its toxic effects in mice to validate its popular use. Adult male Swiss mice (30-35g) were used. The Eta antinociceptive effect (200-800mg/kg, oral route (p.o.)) was evaluated in the acetic acid, formalin, capsaicin and tail-immersion tests. Adverse effects were analyzed using rotarod and open-field tests, body temperature, biochemical analysis and gastric lesions assessment. To evaluate the acute (OECD 423) or sub-acute (OECD 407) toxicity of the Eta, it was administered orally at a single (2000mg/kg) or repeated doses (100-400mg/kg/day for 28 days), respectively. Mortality, behavioral changes, biochemical and hematological parameters were evaluated. The Eta effect on cellular viability also was evaluated. Eta (200-800mg/kg) inhibited the nociception caused by acetic acid (93.9±1.5%), formalin (86.2±10.8%) or capsaicin (75.4±3.3%) without inducing gastric lesions. Moreover, Eta neither altered the body temperature, biochemical parameters, nor forced or spontaneous locomotor activity of mice. The acute administration of the Eta (2000mg/kg) promoted a decrease in blood glucose levels and alanine aminotransferase activity. In the sub-acute toxicity study, Eta increased the aspartate aminotransferase activity (400mg/kg) and platelet distribution width (200mg/kg). Furthermore, Eta did not alter the cellular viability in cortical slices. Eta presents antinociceptive effects and mild toxicity in mice. These results support its traditional use as a potential analgesic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

    Science.gov (United States)

    Guzzo, Luciana S; Romero, Thiago R L; Queiroz-Junior, Celso M; Caliari, Marcelo V; Azevedo, Adolfo O; Perez, Andréa C; Duarte, Igor D G

    2015-10-01

    Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2μg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of β-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. Intraplantar injection of kahweol (40 and 80μg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100μg/paw) prevented action of kahweol (80μg/paw) and the aminopeptidases inhibitor bestatin (400μg/paw) potentiated the antinociceptive effect of kahweol (40μg/paw). Furthermore, kahweol treatment increased the intensity of β-endorphin immunoreactivity in the epithelium of rat paws. The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Antinociceptive and anti-inflammatory effects of Rhodiola rosea L. extract in rats.

    Science.gov (United States)

    Doncheva, Nina D; Mihaylova, Anita St; Getova, Damianka P

    2013-01-01

    Rhodiola rosea (golden root) is a unique phytoadaptagen with immunomodulatory, antioxidant, anti-inflammatory and antinociceptive activity. The aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the alcohol/water extract of Rhodiola rosea roots in rats. Thirty male Wistar rats were used in the study. They were divided in 3 groups (n = 10), treated respectively with saline (controls), Rhodiola rosea extract 50 mg/kg bw and 100 mg/kg bw orally. The antinociceptive effect was evaluated using the hot-plate test, Randall-Sellito test and the formalin test. The hot-plate test evaluates the reaction time of rats which are dropped on a heated surface. The analgesy-meter test exerts a force increased at constant rate. In the formalin test we measured the total time spent in licking the injected paw during the early (0-10 min) and late phase (20-30 min) of test. To study anti-inflammatory effect the carrageenan-induced paw edema was used. The paw volume was measured plethysmometrically at 2, 3 and 4 hours. In the hot-plate test Rhodiola rosea increased in both doses the latency reaction compared with that in the controls. In analgesy-meter test Rhodiola rosea in a dose of 50 mg/kg showed a significant increase of pressure reaction compared with the controls. In the formalin test Rhodiola rosea in a dose of 100 mg/kg significantly decreased the paw licking time during the first phase. In the plethysmometer test Rhodiola rosea extract significantly reduced carrageenan-induced paw edema when compared with the saline-induced edema. The studied extract of Rhodiola rosea exhibited significant analgesic activity in all the pain models used--inhibition of thermal pain, mechanical hyperalgesia and formalin-induced pain behavior. Significant anti-inflammatory activity was observed from Rhodiola rosea extract in carrageenan induced paw edema in rats.

  8. Antinociceptive effect of Lafoensia pacari A. St.-Hil. independent of anti-inflammatory activity of ellagic acid.

    Science.gov (United States)

    Nascimento, Marcus Vinícius Mariano; Galdino, Pablinny Moreira; Florentino, Iziara Ferreira; Sampaio, Bruno Leite; Vanderlinde, Frederico Argollo; de Paula, José Realino; Costa, Elson Alves

    2011-07-01

    This study was performed to determine the antinociceptive and anti-inflammatory activities of ethanolic extract of Lafoensia pacari A. St.-Hil. (PEtExt) stem bark and its fractions using various animal models such as acetic acid-induced abdominal writhing, formalin-induced pain and croton oil-induced ear edema tests. The PEtExt inhibited the acetic acid-induced abdominal writhing, reduced the pain reaction time on both phases of the formalin test and decreased the edema in a dose-dependent manner. Pre-treatment with naloxone did not reverse the antinociceptive effect. Only the ethyl acetate fraction showed antinociceptive and anti-inflammatory effects. Our results also showed that this extract contains compounds with analgesic action independent of anti-inflammatory activity.

  9. 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

    injuries were induced with a thermode, which was heated to 49 degrees C for 5 min under standardized pressure. Clobetasol propionate or placebo cream was applied to the skin 1 h before burn injury, immediately after the injury and every 12 h for the next 3 days. Heat pain detection thresholds (HPDT), heat......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...

  10. Antinociceptive effect and acute toxicity of the essential oil of Hyptis fruticosa in mice.

    Science.gov (United States)

    Menezes, Igor A C; Marques, Maxsuel S; Santos, Thiago C; Dias, Kellyane S; Silva, Aline B L; Mello, Iderjane C M; Lisboa, Ana C C D; Alves, Péricles B; Cavalcanti, Sócrates C H; Marçal, Rosilene M; Antoniolli, Angelo R

    2007-04-01

    The essential oil of the Hyptis fruticosa leaves was analyzed by GC/MS and evaluated for antinociceptive property as well as acute toxicity in mice. The essential oil, at doses of 100, 200, and 400 mg/kg (s.c.), produced significant inhibition of acetic acid-induced writhing, but did not manifest a significant effect in hot-plate test. There was no acute toxicity at doses up to 5 g/kg. Bicyclogermacrene, 1,8-cineole, alpha-pinene, and beta-caryophyllene were the major compounds detected in the essential oil.

  11. Evaluation of thermal antinociceptive effects after intramuscular administration of buprenorphine hydrochloride to American kestrels (Falco sparverius).

    Science.gov (United States)

    Ceulemans, Susanne M; Guzman, David Sanchez-Migallon; Olsen, Glenn H; Beaufrère, Hugues; Paul-Murphy, Joanne R

    2014-08-01

    To evaluate the thermal antinociceptive effects and duration of action of buprenorphine hydrochloride after IM administration to American kestrels (Falco sparverius). 12 healthy 3-year-old American kestrels. Buprenorphine hydrochloride (0.1, 0.3, and 0.6 mg/kg) and a control treatment (saline [0.9% NaCl] solution) were administered IM in a randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus. Adverse effects were monitored for 6 hours after treatment administration. Buprenorphine hydrochloride at 0.1, 0.3, and 0.6 mg/kg, IM, increased thermal threshold for 6 hours, compared with the response for the control treatment. There were no significant differences among buprenorphine treatments. A mild sedative effect was detected at a dose of 0.6 mg of buprenorphine/kg. At the doses tested, buprenorphine hydrochloride resulted in thermal antinociception in American kestrels for at least 6 hours, which suggested that buprenorphine has analgesic effects in this species. Further studies with longer evaluation periods and additional forms of noxious stimuli, formulations, dosages, and routes of administration are needed to fully evaluate the analgesic effects of buprenorphine in American kestrels.

  12. Role of prefrontal cortical calcium-independent phospholipase A2 in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant maprotiline.

    Science.gov (United States)

    Chew, Wee-Siong; Shalini, Suku-Maran; Torta, Federico; Wenk, Markus R; Stohler, Christian; Yeo, Jin-Fei; Herr, Deron R; Ong, Wei-Yi

    2017-01-06

    The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline. Intraperitoneal injections of maprotiline increased iPLA2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of maprotiline was abrogated by iPLA2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of maprotiline. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Antinociceptive effects of tramadol hydrochloride after intravenous administration to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    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.

  14. Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

    Science.gov (United States)

    Risberg, Åse I; Spadavecchia, Claudia; Ranheim, Birgit; Hendrickson, Eli H S; Lervik, Andreas; Haga, Henning A

    2015-05-01

    To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. Prospective, experimental cross-over trial. Nine Norwegian Fjord research foals. Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p buprenorphine. These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  15. Study of antinociceptive effects on acute pain treated by bioactive fractions of Hyptis suaveolens

    Directory of Open Access Journals (Sweden)

    Azmathunnisa Begum

    2016-09-01

    Full Text Available Objective: To investigate the ethanolic extract and its fractions of Hyptis suaveolens (H. suaveolens for antinociceptive and central nervous system depressant effects. Methods: Dried and coarsely powdered aerial parts of plant material were extracted in 80% aqueous ethanol. Further extract was fractionated using solvents of varying polarity. Analgesic properties was assessed using acetic acid-induced writhing and hot plate test and locomotor activity were performed in mice using hole board test. Results: The petroleum ether and ethyl acetate extracts had produced significant analgesic properties and were found to be maximum when tested at 400 mg/kg. Both extracts significantly increased the latency time in hot plate test and the action was antagonised by naloxone. The naloxone was not able to alter H. suaveolens induced antinociceptive effect in writhing test. Conclusions: From the point of central nervous system depressant and good protective effect on chemical and thermal pain stimuli, it indicates that H. suaveolens might have resulted from activation of opioid and/or peripheral receptors.

  16. Effect of amantadine on oxymorphone-induced thermal antinociception in cats.

    Science.gov (United States)

    Siao, K T; Pypendop, B H; Escobar, A; Stanley, S D; Ilkiw, J E

    2012-04-01

    This study examined the effect of amantadine, an N-methyl-d-aspartate receptor antagonist, on the thermal antinociceptive effect of oxymorphone in cats. Six adult healthy cats were used. After baseline thermal threshold determinations, oxymorphone was administered intravenously to maintain plasma oxymorphone concentrations of 10, 20, 50, 100, 200, and 400 ng/mL. In addition, amantadine, or an equivalent volume of saline, was administered intravenously to maintain a plasma amantadine concentration of 1100 ng/mL. Thermal threshold and plasma oxymorphone and amantadine concentrations were determined at each target plasma oxymorphone concentration. Effect maximum models were fitted to the oxymorphone concentration-thermal threshold data, after transformation in % maximum response. Oxymorphone increased skin temperature, thermal threshold, and thermal excursion (i.e., the difference between thermal threshold and skin temperature) in a concentration-dependent manner. No significant difference was found between the amantadine and saline treatments. Mean ± SE oxymorphone EC(50) were 14.2 ± 1.2 and 24.2 ± 7.4 ng/mL in the amantadine and saline groups, respectively. These values were not significantly different. Large differences in oxymorphone EC(50) in the saline and amantadine treatment groups were observed in two cats. These results suggest that amantadine may decrease the antinociceptive dose of oxymorphone in some, but not all, cats. © 2011 Blackwell Publishing Ltd.

  17. Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Ting-Yi Chien

    2016-02-01

    Full Text Available The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO synthase (iNOS, cyclooxygenase (COX-2 expressions, and NO and prostaglandin E2 (PGE2 production, but induced heme oxygenase (HO-1 expression in a dose-dependent manner in lipopolysaccharide (LPS-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP, the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP-13 and COX-2 expressions of interleukin (IL-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

  18. Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis.

    Science.gov (United States)

    Chien, Ting-Yi; Huang, Steven Kuan-Hua; Lee, Chia-Jung; Tsai, Po-Wei; Wang, Ching-Chiung

    2016-02-18

    The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E₂ (PGE₂) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

  19. Corticosteroid effects on morphine-induced antinociception as a function of two types of corticosteroid receptors in brain

    NARCIS (Netherlands)

    Ratka, A; Veldhuis, H D; De Kloet, E R

    The antinociceptive effect of parenterally and intracerebroventricularly injected morphine and beta-endorphin in adrenalectomized rats and in adrenalectomized rats treated with adrenal steroids was examined employing the hot-plate method. (1) Adrenalectomy sensitized the rats to an analgesic effect

  20. Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models

    Directory of Open Access Journals (Sweden)

    Valiollah Hajhashemi

    2013-04-01

    Full Text Available Objective: This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Materials and Methods: 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. Results: 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%. Conclusion: 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.  

  1. Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models.

    Science.gov (United States)

    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.

  2. Peripheral antinociception and anti-inflammatory effects of sulphated polysaccharides from the alga Caulerpa mexicana.

    Science.gov (United States)

    Carneiro, José Gerardo; Rodrigues, José Ariévilo Gurgel; de Sousa Oliveira Vanderlei, Edfranck; Souza, Ricardo Basto; Quinderé, Ana Luíza Gomes; Coura, Chistiane Oliveira; de Araújo, Ianna Wivianne Fernandes; Chaves, Hellíada Vasconcelos; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2014-10-01

    Sulphated polysaccharides from marine algae are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of sulphated polysaccharides from the green marine alga Caulerpa mexicana (Cm-SPs) in nociceptive and inflammatory models in rodents. Cm-SPs (10 or 20 mg/kg), administered i.v. in Swiss mice, significantly reduced nociceptive responses, as measured by the number of writhes in response to acetic acid. Cm-SPs (10 or 20 mg/kg) also reduced second-phase responses in the formalin test, but did not exhibit a significant antinociceptive effect in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. Cm-SPs (5, 10 or 20 mg/kg), administered s.c. in wistar rats 1 hr before carrageenan, dextran, histamine or serotonin, were tested in paw oedema models. Cm-SPs (10 or 20 mg/kg) reduced carrageenan-induced paw oedema and myeloperoxidase activity in the paw. In addition, Cm-SPs (20 mg/kg) inhibited dextran- or histamine-induced paw oedema, but not serotonin-induced oedema, suggesting that histamine is the major target of Cm-SPs anti-oedematogenic activity. Finally, Cm-SPs (20 mg/kg) administered in mice did not show significant signs of toxicity. In conclusion, Cm-SPs appear to be promising natural modulatory agents for pain and inflammatory conditions. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models

    Science.gov (United States)

    Hajhashemi, Valiollah; Klooshani, Vahid

    2013-01-01

    Objective: This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Materials and Methods: 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. Results: 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%. Conclusion: 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. PMID:25050274

  4. Intraventricular gabapentin is antinociceptive and enhances systemic morphine antinociception in rat tail flick test

    Directory of Open Access Journals (Sweden)

    Shamsi Meymandi M.

    2007-07-01

    Full Text Available Background: Gabapentin has been recently considered as an analgesic in neurpathic pain through spinal site of action. In addition co-administration of low dose of morphine with gabapentin, is proposed not only to reduce side effects, tolerance, and dependency of morphine but also has some analgesic effects. In this study, the analgesic effect of intracerebroventricular (ICV gabapentin and its effect on morphine antinociception were investigated in tail-flick test.Methods: An intraventricular cannula was surgically inserted into ventricle space of rat brain. The latency time was measured after microinjection of 100,300,600 and 1000 µg of gabapentin or normal saline (sham. After determination of subanalgesic dose of gabapentin (300µg, the combinational groups received subanalgesic and low dose of morphine (2 and 7 mg /kg intraperitoneally, thirty minutes prior to gabapentin administration. Time response curve and Area Under the Curve (AUC, as antinociceptive index, were compared among the groups.Results: Intraventricular gabapentin showed analgesic effects at 600 µg (ICV. The combination of subanalgesic doses of gabapentin (300 µg ICV and morphine (2 mg /kg i.p increased significantly time-response curve and AUC compared to other groups. In addition, the analgesic response following co-administration of gabapentin (300 µg ICV and analgesic dose of morphine was increased significantly compared to the sham and gabapentin group.Conclusion: The results demonstrated that intraventricular gabapentin has analgesic effect in transient model of pain and enhances morphine antinociception through cerebral site of action.

  5. Study of antinociceptive effect of isolated fractions from Petiveria alliacea L. (tipi) in mice.

    Science.gov (United States)

    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.

  6. 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 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.

  7. Evaluation of antinociceptive and antiinflammatory effects of Croton pullei var. glabrior Lanj. (Euphorbiaceae

    Directory of Open Access Journals (Sweden)

    Fábio F. Rocha

    Full Text Available Croton pullei var. glabrior Lanj. (Euphorbiaceae is a liana, vastly distributed in the Amazonian Forest. In the folk medicine, several plants of the Croton genus have been used with therapeutic purposes in pathologies that involve painful and inflammatory diseases which justify this work. The aim of this study was to investigate the antinociceptive and antiinflammatory activities of the C. pullei leaves methanol extract (MECP. MECP reduced in a dose-dependent manner the number of acetic acid-induced abdominal writhing (1.2% in mice, suggesting an antinociceptive activity of the plant. On the other hand, MECP did not significantly modify the reactivity to the thermal stimulation in the hot-plate test and the reactivity to the chemical stimulation in the formalin test first phase, indicating a non-opioid mechanism. MECP reduced the formalin-induced nociception in the second phase, inhibited the croton oil-induced ear edema and reduced the leukocytes migration in the test of the carrageenan-induced peritonitis, indicating an antiinflammatory activity. Although the mechanisms that underlie these plant effects are not completely elucidated, these results appear to support the potential medicinal use of Croton pullei var. glabrior Lanj. against painful and inflammatory diseases.

  8. Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris.

    Science.gov (United States)

    Taherian, Abbas Ali; Babaei, Mahdi; Vafaei, Abbas Ali; Jarrahi, Morteza; Jadidi, Majid; Sadeghi, Hassan

    2009-01-01

    Previous investigation has shown that Thymus Vulgaris (TV) modulates pain. The aim of this work was to examine the role of TV on acute and chronic pain and compares its effect with dexamethasone (DEX) and stress (ST) by using hot plate, tail flick and formalin tests in mice. In this study male albino mice (25-30 g.) in 21 groups (n=147) were used. TV (100, 500 and 1000 mg/kg), DEX (0.5, 1 and 2 mg/kg) and vehicle (VEH) were injected 30 minutes before pain assessment tests. Stress was applied by 1 min swimming in cold water (18-22 degrees ). Acute and chronic pain was assessed by hot plate, tail flick and formalin tests. For assessment of the role of opioid receptors in antinoceception of TV extract, Naloxon (NAL, 2mg/kg, ip) as opioid receptor antagonist was injected before the injection of the more effective dose (500 mg/kg) of TV extract. Results indicated that TV, DEX and ST have analgesic effects in all tests (P<0.01 in comparison with control group). Above findings showed that TV extract, DEX and ST have modulatory effects on acute and chronic pain. Further research is required to determine the mechanisms by which TV extract has an inhibitory effect on pain sensation.

  9. Recombinant ecto-5'-nucleotidase (CD73 has long lasting antinociceptive effects that are dependent on adenosine A1 receptor activation

    Directory of Open Access Journals (Sweden)

    Zylka Mark J

    2010-04-01

    Full Text Available Abstract Background Ecto-5'-nucleotidase (NT5E, also known as CD73 hydrolyzes extracellular adenosine 5'-monophosphate (AMP to adenosine in nociceptive circuits. Since adenosine has antinociceptive effects in rodents and humans, we hypothesized that NT5E, an enzyme that generates adenosine, might also have antinociceptive effects in vivo. Results To test this hypothesis, we purified a soluble version of mouse NT5E (mNT5E using the baculovirus expression system. Recombinant mNT5E hydrolyzed AMP in biochemical assays and was inhibited by α,β-methylene-adenosine 5'-diphosphate (α,β-me-ADP; IC50 = 0.43 μM, a selective inhibitor of NT5E. mNT5E exhibited a dose-dependent thermal antinociceptive effect that lasted for two days when injected intrathecally in wild-type mice. In addition, mNT5E had thermal antihyperalgesic and mechanical antiallodynic effects that lasted for two days in the complete Freund's adjuvant (CFA model of inflammatory pain and the spared nerve injury (SNI model of neuropathic pain. In contrast, mNT5E had no antinociceptive effects when injected intrathecally into adenosine A1 receptor (A1R, Adora1 knockout mice. Conclusion Our data indicate that the long lasting antinociceptive effects of mNT5E are due to hydrolysis of AMP followed by activation of A1R. Moreover, our data suggest recombinant NT5E could be used to treat chronic pain and to study many other physiological processes that are regulated by NT5E.

  10. Antinociceptive effect of propolis from two different vegetations

    Directory of Open Access Journals (Sweden)

    Emanuelle Karine Frota Batista

    2015-11-01

    Full Text Available The aim of this study was to evaluate the analgesic effect of propolis, comparing solutions prepared from propolis obtained from the apiary of the Centre for Agricultural Sciences (CCA of the Federal University of Piauí, with the extract from the Apis Flora Laboratory. Forty eight mice were divided into six groups treated with hydroethanol solution (vehicle, 20mL/Kg, p.o., dipyrone (positive control, 50mL/Kg, p.o., propolis solution 10% (obtained from CCA and Apis Flora, 20mL/Kg, p.o. and propolis 20% solution (obtained from CCA and Apis Flora, 20mL/Kg, p.o.. The nociceptive stimulus was induced by intraperitoneal (i.p. administration of 0.6% acetic acid 20 minutes after administration of each treatment. The number of writhing was performed, for a period of 20 minutes, and the inhibition percentage of the painful sensation provided by each treatment were calculated. The results showed that the control group, treated with hydroethanol solution, was significantly different from all others, and those treated with propolis solution at 10% and 20% from, both sources do not differ significantly from each other and not the positive control, showing similar analgesic effect.

  11. Anti-inflammatory and antinociceptive effects of Sterculia striata A. St.-Hil. & Naudin (Malvaceae) in rodents.

    Science.gov (United States)

    Silva, Francilene V; Oliveira, Irisdalva S; Figueiredo, Kayo A; Júnior, Francisco B Melo; Costa, Danielly A; Chaves, Mariana H; Amaral, Maurício P M; Almeida, Fernanda R C; Oliveira, Francisco A; Oliveira, Rita C M

    2014-06-01

    The present work reports the anti-inflammatory and antinociceptive activities of the ethanol extract obtained from the stem bark of Sterculia striata A. St.-Hil. & Naudin (Ss-EtOH) in the experimental models of edema induced by carrageenan, dextran, or histamin and nociception induced by chemical stimuli, such as acetic acid, formalin, capsaicin, or glutamate. The Ss-EtOH (50 mg/kg) promoted a marked inhibition on the hind paw edema induced by carrageenan or dextran (30% and 73%, respectively). Besides, Ss-EtOH (25 mg/kg) exhibited a slight activity (30%) on the hind paw edema induced by histamin. The Ss-EtOH (12.5 and 25 mg/kg) showed the antinociceptive activity on chemical stimuli induced by acetic acid (65.59% and 38.37%, respectively), formalin, in the initial (35.08% and 31.5%, respectively) and late phases (44.09% and 83.57%, respectively), capsaicin (43.77% and 51.31%, respectively), or glutamate (36.6% and 52.12%, respectively). Regarding the possible mechanism involved in the antinociceptive effect, Ss-EtOH (12.5 mg/kg) showed a decrease in the antinociceptive effect (65.8%) in the acetic acid model after pretreatment with naloxone. Thus, opioid mechanisms might be underlying this response.

  12. Peripheral and central antinociceptive effects of the butanolic fraction of Byrsonima verbascifolia leaves on nociception-induced models in mice.

    Science.gov (United States)

    Saldanha, A A; Siqueira, J M; Castro, A H F; Matos, N A; Klein, A; Silva, D B; Carollo, C A; Soares, A C

    2017-02-01

    Byrsonima verbascifolia (Malpighiaceae), commonly known as 'murici', is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.

  13. Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

    National Research Council Canada - National Science Library

    Nóbrega Neto, Pedro I; Luna, Stelio P L; Queiroz-Williams, Patricia; Mama, Khursheed R; Steffey, Eugene P; Carregaro, Adriano B

    2013-01-01

    This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index...

  14. The Antinociceptive Effects of Tualang Honey in Male Sprague-Dawley Rats: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Che Badariah Abd Aziz

    2014-10-01

    Full Text Available Tualang honey (蜂蜜 Fēng Mì is known to have anti-inflammatory property, but its antinociceptive property has not been extensively investigated. In this study, we examined the preemptive effects on administering different doses of Tualang honey and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty-five male Sprague-Dawley rats were randomized into five groups (n=7 and each group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg or prednisolone (10 mg/kg for 10 days. The response to noxious thermal stimulus was assessed using tail flick test on Day 10. The well-being of the rats was also assessed by monitoring their food intake and body weight. Data were analyzed using one-way Analysis of Variance (ANOVA with post-hoc Scheffe's test and P value less than 0.05 was considered significant. In tail flick test, the tail flick latency time was significantly higher in the groups that received 1.2 g/kg and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the control group (P<0.05. There was significant reduction in the total food pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg and 2.4 g/kg compared to controls; however, the body weight gain was only significantly reduced in the prednisolone group. All the parameters were not significantly affected in the group receiving 0.2 g/kg of Tualang honey. In conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg and prednisolone (10 mg/kg had reduced the pain responses. The reduced weight gain in the prednisolone group is an unwanted effect due to its metabolic and central actions. Further studies are required to confirm the antinociceptive effects and elucidate the mechanism of antinociceptive action of Tualang honey in the rats.

  15. Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    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.

  16. 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)

  17. Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats

    Science.gov (United States)

    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

  18. The anti-nociceptive effect and the possible mechanism of acupoint stimulation caused by chemical irritants in the bee venom pain model.

    Science.gov (United States)

    Chen, Hui-Sheng; Qu, Fang; He, Xiang; Liao, Dan; Kang, Shuang-Ming; Lu, Su-Jie

    2010-10-08

    Many studies have demonstrated the anti-nociceptive and anti-inflammatory effects of injecting bee venom (BV) into the Zusanli (ZSL) acupoint in rats. The present study was designed to determine whether the injection of other chemical irritants, such as formalin and complete Freund's adjuvant (CFA), into the ZSL acupoint can produce anti-nociceptive and anti-inflammatory effects in the BV pain model and to determine the possible mechanisms underlying these effects. First, the effects of injecting BV, formalin, CFA, or saline into the ZSL acupoint on intraplantar BV-induced persistent spontaneous pain, mechanical hyperalgesia, and inflammatory swelling of the injected paw were observed. BV, formalin, CFA, and saline injection into the ZSL acupoint significantly inhibited intraplantar BV-induced persistent spontaneous nociception (PSN) and mechanical hyperalgesia but had no effect on intraplantar BV-induced inflammatory swelling. Next, the effects of pretreatment with naloxone (5mg/kg, ip) or injection of 0.15% capsaicin into the ZSL acupoint on the anti-nociceptive effect of BV acupuncture (BVA) were observed. Pretreatment with naloxone had no effect on the BVA-induced anti-nociceptive effect, intraplantar BV-induced PSN, and mechanical hyperalgesia. Pretreatment with capsaicin produced partial blockage of the BVA-induced anti-nociceptive effect on PSN, but it had no effect on BVA-induced anti-nociception of mechanical hyperalgesia. These results suggest that (1) chemical irritant acupuncture produces the anti-nociceptive effect but not the anti-inflammatory effect in the BV pain model, and (2) chemical irritant acupuncture-induced analgesia is a common mechanism that is not specific to BV acupuncture. Our results also suggest that the BVA-induced anti-nociceptive mechanism is partially mediated by capsaicin-sensitive primary afferent fibers but not by endogenous mu opioid receptors in the BV pain model. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Topical ketorolac has no antinociceptive or anti-inflammatory effect in thermal injury

    DEFF Research Database (Denmark)

    Møiniche, S; Pedersen, J L; Kehlet, H

    1994-01-01

    This study investigated the antinociceptive and anti-inflammatory effect of a topical non-steroidal anti-inflammatory drug in human thermal injury. Twelve healthy unmedicated volunteers had identical burn injuries produced on the medial side of both calves with a 49 degrees C 15 x 25 mm thermode....... and MPDT, an increase in EI and development of mechanical hyperalgesia (P nociceptive or inflammatory variables studies (P > 0.2)........ Ketorolac gel or placebo were randomly applied on the right or left calf 1.5 h before burn injury, immediately after burn injury and 6 and 12 h later in a double-blind trial where every subject served as his own control. Heat pain detection thresholds (HPDT), head pain tolerance (HPT), mechanical pain...

  20. Preliminary investigation of the thermal antinociceptive effects of codeine in cats.

    Science.gov (United States)

    Steagall, Paulo V M; Monteiro, Beatriz P; Lavoie, Anne-Marie; Troncy, Eric

    2015-12-01

    The aim of this study was to evaluate the potential thermal antinociceptive effects of oral administration of a single dose of codeine in cats compared with positive (buprenorphine) and negative (saline 0.9%) controls. Six adult healthy cats weighing 5.14 ± 0.6 kg were used. Skin temperature and thermal thresholds (TTs) were evaluated using a wireless device (Topcat Metrology) at baseline, 0.5, 1, 3, 6 and 10 h after treatment. In period 1, TTs were evaluated after subcutaneous administration of saline 0.9%. In period 2, cats were administered either oral codeine (10 mg total, 2.0 ± 0.2 mg/kg) or buccal buprenorphine (0.04 mg/kg) in a cross-over, blinded study design. Half of the volume of buprenorphine was administered into each cheek pouch. Δ TT (difference between TTs after and before treatment) was used for data comparison. Mean ± SD data were analyzed using one-way ANOVA followed by Dunnett's or Tukey's test when appropriate (P codeine. Buprenorphine increased Δ TT at 3 h (2.7 ± 3.3°C) when compared with baseline or saline (P 47.6°C at any time point in four cats. The mean highest temperature recorded in the two other cats in that group was 54.5 and 52.8°C at 3 h. At the dose administered, codeine did not produce thermal antinociception. Mild increases in TT after buccal buprenorphine might be related to the first-pass effect after drug swallowing, drug spillage during administration and/or individual variability. These factors should be taken in to consideration when administering buprenorphine by this route in the clinical setting. © ISFM and AAFP 2015.

  1. Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

    Science.gov (United States)

    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.

  2. Study the Antinociceptive Effect of Intracerebroventricular Injection of Aqueous Extract of Origanum Vulgare Leaves in Rat: Possible Involvement of Opioid System

    Science.gov (United States)

    Pahlavan, Yasaman; Sepehri, Gholamreza; Sheibani, Vahid; Afarinesh khaki, Mohammadreza; Gojazadeh, Morteza; Pahlavan, Bahare; Pahlavan, Fereshteh

    2013-01-01

    Objective(s): The aim of study was to investigate the antinociceptive effect of intracerebroventricular (ICV) microinjection of Origanum vulgare (ORG) extract and possible involvement of opioid receptors. Materials and Methods: Cannula was inserted into left ventricle of male rats. Five days after surgery Tail Flick Latency (TFL) was measured after ICV microinjection of, ORG (1, 3 and 6 µg / rat). Effective dose of ORG was injected ICV in concomitant with morphine (2 mg/kg, IP), naloxone (2 mg / kg, IP) and saline (0.5 µl/rat) and TFL was recorded. Results: The co- administration of ORG extract with morphine showed a significant increase in TFL and naloxone, pretreatment significantly inhibited the antinociceptive activity of ORG and morphine. Conclusion: The aqueous extract of ORG possesses antinociceptive activities in the tail-flick test in a dose dependent manner. ORG - induced antinociception may have been mediated by opioid systems. PMID:24379969

  3. The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

    Science.gov (United States)

    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.

  4. Potentiation of the antinociceptive effect of clomipramine by a 5-ht1A antagonist in neuropathic pain in rats

    Science.gov (United States)

    Ardid, D; Alloui, A; Brousse, G; Jourdan, D; Picard, P; Dubray, C; Eschalier, A

    2001-01-01

    The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5-HT1A antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug. The purpose of this work was to evaluate the combination of an antidepressant and a 5-HT1A antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipramine and a 5-HT1A antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats). The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5-HT1A antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine. These new findings argue for using the combination of an antidepressant and a 5-HT1A antagonist in human neuropathic pain therapy. PMID:11226143

  5. Evaluation of Anti-Inflammatory and Anti-Nociceptive Effects of Defatted Fruit Extract of Olea europaea.

    Science.gov (United States)

    Sahranavard, Shamim; Kamalinejad, Mohammad; Faizi, Mehrdad

    2014-01-01

    Fruits of Olea europaea L. have been used for centuries in folk medicine to treat many inflammatory diseases. In order to evaluate the anti-nociceptive activities of the methanolic and aqueous extracts of defatted fruits of O. europaea, formalin test was used and for evaluation of anti-inflammatory effects of the extract, the volume of paw edema was measured. The results revealed that both extracts did not exhibit significant analgesic activity in the first phase of formalin test, whereas methanolic extract at the 600 mg/Kg dose and aqueous extract at the 450 and 600 mg/Kg doses could inhibit induced pain in the second phase of formalin test. Furthermore, the results of paw edema volume measurement indicated that the aqueous extract has anti-inflammatory effects at dose of 600 mg/Kg. Induced anti-nociception by aqueous olive extract was not reversed by naloxone, which indicates that the opioid receptors are not involved in the analgesic effects of the extracts. The present data pointed out that the extracts of olive defatted fruit have anti-nociceptive and anti-inflammatory effects in rats but further studies are needed to elucidate the mechanism(s) of action and active components which are involved in analgesic and anti-inflammatory effects.

  6. Antinociceptive effect of Zanthoxylum rhoifolium Lam. (Rutaceae) in models of acute pain in rodents.

    Science.gov (United States)

    Pereira, S S; Lopes, L S; Marques, R B; Figueiredo, K A; Costa, D A; Chaves, M H; Almeida, F R C

    2010-05-27

    Zanthoxylum rhoifolium Lam. (Rutaceae) is locally known as "mamica de cadela", and its bark is popularly used for toothache and earache. The objective of this study was to investigate the antinociceptive effect of the ethanolic extract from this species' stem bark (EtOH), its fractions of partition (hexane-HEX, ethyl acetate-AcOEt, aqueous-AQ) and lupeol (a triterpene obtained from HEX) in models of acute pain. Male and female Swiss mice (25-35 g, n=6-12 animals/group) were used to assess acute toxicity and nociception (Animal Ethics Committee/UFPI, No. 09/2008). Acute toxicity was studied up to 2 g/kg p.o. of EtOH. In the formalin test (2%, 20 microL/paw), the licking time of the stimulated paw was quantified during the first 5 min (first phase) and at 15-30 min (second phase), 1h after oral treatment with EtOH, HEX, AcOEt or saline, and 30 min after use of morphine-MOR (5 mg/kg i.p.). The same response evoked by capsaicin (2 microg/20 microL/paw) was quantified during 5 min, after administration of EtOH, HEX, AcOEt, AQ, saline and MOR. The licking time of the paw that was stimulated with glutamate (10 micromol/20 microL) was measured (15 min) after treatment with EtOH, HEX, AcOEt, AQ, lupeol, saline or MK801 (0.03 mg/kg, i.p.). Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of EtOH (250 mg/kg p.o.) and HEX (500 mg/kg p.o.). The animals did not exhibit any acute toxicity to EtOH (up to 2 g/kg p.o.), so it was not possible to calculate the LD50. EtOH, HEX and AcOEt (62.5-250 mg/kg) produced a significant antinociceptive effect in the formalin and capsaicin tests. However, AQ was ineffective. EtOH, HEX, AcOEt and lupeol reduced the glutamate-evoked nociceptive response, but AQ had no effect. EtOH and HEX did not alter the locomotion of animals in the open-field or rota-rod tests, which suggest a lack of a central depressant effect. The results confirm the popular use of Zanthoxylum

  7. Antinociceptive Effect of Cinnamon Extract on Formalin Induced Pain in Rat

    Directory of Open Access Journals (Sweden)

    AR Vahidi Merjardi

    2009-07-01

    Full Text Available Introduction: Since time memorial, herbal medicine has played an important role for relief of various symptoms including pain relief. Many researches have focused on the curative as well as antinociceptive effects of herbal extracts. Cinnamon Zeylanicum has long been prescribed in traditional medicine for the treatment of inflammatory-related diseases such as rheumatisms, bronchitis and muscle pains. However, there is little if any scientific research indicating this effect Methods: This experimental study was carried out in Shaheed Sadoughi Medical School on 25 Wistar Rats (200-300grams randomly divided into 5 groups. In this study, the analgesic effect of intraperitoneal administration of hydro-alcoholic Cinnamon extract in different doses (50,100,500mg/kg was assessed by using Formalin Test (for chronic pain during 1hr. post Formalin injection. Results: Our results indicated that cinnamon extract in high dose (500mg/kg decreased the chronic pain intensity in the 2nd phase of formalin test. This analgesic effect was significant (P<0.001 as compared with sham group, but the lower doses (50 &100mg/kg of cinnamon extract did not show any analgesic effect on chronic pain in Formalin Test. Conclusion: Data from this study confirms the analgesic effect of high doses (500mg/kg of cinnamon extract on chronic pain in Formalin Test which may be due to anti-inflammatory effect of this plant material.

  8. Antinociceptive effect of Valeriana fauriei regulates BDNF signaling in an animal model of fibromyalgia.

    Science.gov (United States)

    Lee, Hwayoung; Im, Jiyun; Won, Hansol; Kim, Jun Young; Kim, Hyung-Ki; Kwon, Jun-Tack; Kim, Young Ock; Lee, Sanghyun; Cho, Ik-Hyun; Lee, Sang Won; Kim, Hak-Jae

    2018-01-01

    The genus Valeriana has been widely used in popular medicine for centuries, to treat sleep disorders, anxiety, epilepsy and insomnia. Recent studies have focused on the novel pharmacological effects of Valeriana fauriei Briq. (VF) species. Previous studies have attempted to determine the pharmacological functions of Valeriana in various human diseases, particularly with regards to its neuroprotective effects, and its ability to reduce pain and stress. The present study constructed an animal model of fibromyalgia (FM), which was induced by intermittent cold stress with slight modification. Subsequently, the study aimed to determine whether VF exerts antinociceptive effects on the FM‑like model following oral administration of VF extracts. The effects of VF extracts on the FM model were investigated by analyzing behavioral activity, including pain, and detecting protein expression. In the behavioral analysis, the results of a nociception assay indicated that the pain threshold was significantly decreased in the FM group. Subsequently, western blotting and immunohistochemical analyses of the hippocampus demonstrated that the protein expression levels of brain‑derived neurotrophic factor (BDNF) and phosphorylated‑cAMP response element‑binding protein were downregulated in the FM group. Conversely, VF restored these levels. These results suggested that the effects of VF extract on a model of FM may be associated with its modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. In conclusion, the mechanism underlying the protective effects of VF as a therapeutic agent against FM may involve the BDNF signaling pathway.

  9. Evaluation of the antinociceptive and anti-inflammatory effects of essential oil of Nepeta pogonosperma Jamzad et Assadi in rats

    Directory of Open Access Journals (Sweden)

    Ali Taskina

    2012-10-01

    Full Text Available Abstract Background and the purpose of study Concerning the different effects of essential oils from Nepeta genus on the central nervous system including pain killing effect, this study was designed to evaluate the antinociceptive and anti-inflammatory effects of essential oil of Nepeta pogonosperma Jamzad et Assadi (NP, a recently identified species. Methods Air-dried aerial parts of NP were hydrodistillated and GC-MS analysis of obtained essential oil was conducted. Total 24 male Wister rats weighing 225 ± 25 gm were studied. Essential oil of NP was administered intraperitoneally at the doses of 50 mg/kg, 100 mg/kg and 200 mg/kg for the experimental groups. Control rats received equal volume (2 ml/kg of normal saline. Antinociception was assessed by tail flick test (after 30 minutes and formalin test (for further 60 minutes. Then the animal was sacrificed and the paw edema was measured using a water plethysmometer. Results 4aα,7α,7aβ-nepetalactone and 1,8-cineole were found as the main concentrated components of NP essential oil. All the doses of NP showed antinociception. NP 200 mg/kg reduced the pain sensation in tail flick (p Conclusion This study reveals that the essential oil of NP may minimize both the acute and chronic forms of nociception and may have potent role against inflammation, but the dose should be maintained precisely to obtain the intended effect.

  10. Antinociceptive and Anti-Inflammatory Effects of Octacosanol from the Leaves of Sabicea grisea var. grisea in Mice

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    Emiliano Barreto

    2012-02-01

    Full Text Available Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae, an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain, but significantly inhibited the licking time in second phase (inflammatory pain of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the

  11. Antinociceptive and anti-inflammatory effects of the essential oil of Eugenia candolleana DC., Myrtaceae, on mice

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    Adriana G. Guimarães

    Full Text Available Eugenia candolleana DC. (Myrtaceae, commonly known as "murta" or "murtinha", is a plant species without any chemical or pharmacological study described in the literature. It has been popularly used for the treatment of pain and fever. This report aimed to investigate the possible antinociceptive and anti-inflammatory effects of the essential oil extracted from fresh leaves of Eugenia candolleana DC. (EOEc in rodents. Following intraperitoneal injection, EOEc (25, 50 and 100 mg/kg reduced the number of writhes significantly in a writhing test and the number of paw licks during phase two of formalin test (p < 0.001. However, administration of EOEc did not alter the time of reaction in hot plate test. Furthermore, EOEc inhibited (p < 0.01 the carrageenan-induced leukocyte migration to the peritoneal cavity. These results indicate antinociceptive and anti-inflammatory properties of EOEc probably mediated via inhibition of prostaglandin synthesis or other peripherally pathway.

  12. 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.

  13. Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents.

    Science.gov (United States)

    Lima Cavendish, Rodrigo; de Souza Santos, Jandson; Belo Neto, Reinaldo; Oliveira Paixão, Ailma; Valéria Oliveira, Juciele; Divino de Araujo, Edilson; Berretta E Silva, Andresa Aparecida; Maria Thomazzi, Sara; Cordeiro Cardoso, Juliana; Zanardo Gomes, Margarete

    2015-09-15

    Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models. The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed. Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of

  14. 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.

  15. Antinociceptive and antispasmodic effects of the essential oil of Ocimum micranthum: potential anti-inflammatory properties.

    Science.gov (United States)

    Pinho, João Paulo de; Silva, Andressa Santa; Pinheiro, Bruno Gonçalves; Sombra, Igor; Bayma, Joaquim de Carvalho; Lahlou, Saad; Sousa, Pergentino José da Cunha; Magalhães, Pedro Jorge

    2012-05-01

    The antinociceptive and antispasmodic properties of the essential oil of OCIMUM micranthum (EOOM) were characterized. In mice, EOOM (15-100 mg · kg (-1), p. o.) reduced both the writhing responses induced by acetic acid and the licking-time induced by formalin, being inert on the hot plate test. In rat trachea, EOOM relaxed sustained contractions induced by KCl or carbachol (CCh). Its constituents, ( E)- [( E)-MC] and ( Z)-methyl cinnamate [( Z)-MC], reproduced several effects of EOOM. Inhaled as aerosol, EOOM prevented tracheal hyperresponsiveness to KCl or CCh in ovalbumin-sensitized animals after antigen challenge. Thus, EOOM exerts peripheral analgesia in nociception of inflammatory origin and has antispasmodic actions on rat airways under an inflammatory environment. Its effects are mainly due to ( E)-MC, which makes this substance potentially interesting for studies involving conjunctly smooth muscle cells, nociception, and inflammation. Other EOOM constituents also appear to be involved in its pharmacological actions. © Georg Thieme Verlag KG Stuttgart · New York.

  16. 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.

  17. Antioxidant and Antinociceptive Effects of Citrus limon Essential Oil in Mice

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    Lidianne Mayra Lopes Campêlo

    2011-01-01

    Full Text Available The antioxidant and antinociceptive activities of Citrus limon essential oil (EO were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/kg significantly reduced the number of writhes, and, at highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses, this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO.

  18. Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats.

    Science.gov (United States)

    Simón-Arceo, Karina; González-Trujano, Ma Eva; Coffeen, Ulises; Fernández-Mas, Rodrigo; Mercado, Francisco; Almanza, Angélica; Contreras, Bernardo; Jaimes, Orlando; Pellicer, Francisco

    2017-07-12

    Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists. Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans. Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects. Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes. The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

    Directory of Open Access Journals (Sweden)

    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

  20. Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    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.

  1. Anti-Nociceptive And Anti-Inflammatory Effects Of A Nigerian ...

    African Journals Online (AJOL)

    The study investigated the anti-nociceptive and anti-inflammatory properties of a Nigerian Polyherbal Health Tonic tea aqueous extract (PHT) in rodents of both sexes. 100 - 500 mg kg–1 ... PHT was also shown to be more protective than acetylsalicylic acid (ASA) in the castor oil- induced diarrhea model, which suggests the ...

  2. Anti-nociceptive effect of total alkaloids isolated from the seeds of ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical .... injection, and the time of the animal spent for licking the injected paw was recorded. Tail-flick test. Antinociceptive activity of TA was further assessed using the tail-flick test [17]. Mice were.

  3. Calea zacatechichi dichloromethane extract exhibits antidiarrheal and antinociceptive effects in mouse models mimicking irritable bowel syndrome.

    Science.gov (United States)

    Sałaga, M; Kowalczuk, A; Zielinska, M; Błażewicz, A; Fichna, J

    2015-10-01

    Calea zacatechichi Schltdl. (Asteraceae alt. Compositae) is a Mexican plant commonly used in folk medicine to treat respiratory and gastrointestinal (GI) disorders. The objective of this study is to characterize the effect of C. zacatechichi extracts in mouse models mimicking the symptoms of irritable bowel syndrome (IBS). Powdered C. zacatechichi herb (leaves, stems, and flowers) was extracted with methanol. Methanolic extract was filtered and evaporated giving methanolic fraction. The residue was extracted with dichloromethane (DCM). Methanolic and DCM (200 mg/kg, per os) extracts were screened for their effect on GI motility in several in vitro tests, and the antidiarrheal and antinociceptive effects were assessed using mouse models. The influence of the DCM extract on motoric parameters and exploratory behaviors was also assessed. Finally, the composition of C. zacatechichi DCM extract was qualitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) method. C. zacatechichi DCM extract significantly inhibited the contractility of mouse colon in vitro (IC50 = 17 ± 2 μg/ml). Administration of the DCM extract in vivo (200 mg/kg, per os) significantly prolonged the time of whole GI transit (46 ± 1 vs. 117 ± 27 min for control and DCM-treated animals, respectively; P = 0.0023), inhibited hypermotility, and reduced pain in mouse models mimicking functional GI disorders. Our findings suggest that constituents of the C. zacatechichi DCM extract exhibit antidiarrheal and analgesic activity. The extract may thus become an attractive material for isolation of compounds that may be used as a supplementary treatment for pain and diarrhea associated with IBS in the future.

  4. 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.

  5. 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.

  6. Evaluation of the antinociceptive and anti-inflammatory effects of essential oil of Nepeta pogonosperma Jamzad et Assadi in rats

    Directory of Open Access Journals (Sweden)

    Saeed Semnanian

    2012-10-01

    Full Text Available Background and the purpose of study Concerning the different effects of essential oils from Nepeta genus on the central nervous system including pain killing effect, this study was designed to evaluate the antinociceptive and anti-inflammatory effects of essential oil of Nepeta pogonosperma Jamzad et Assadi (NP, a recently identified species.MethodsAir-dried aerial parts of NP were hydrodistillated and GC-MS analysis of obtained essential oil was conducted. Total 24 male Wister rats weighing 225 +/- 25 gm were studied. Essential oil of NP was administered intraperitoneally at the doses of 50 mg/kg, 100 mg/kg and 200 mg/kg for the experimental groups. Control rats received equal volume (2 ml/kg of normal saline. Antinociception was assessed by tail flick test (after 30 minutes and formalin test (for further 60 minutes. Then the animal was sacrificed and the paw edema was measured using a water plethysmometer.Results4aalpha,7alpha,7abeta-nepetalactone and 1,8-cineole were found as the main concentrated components of NP essential oil. All the doses of NP showed antinociception. NP 200 mg/kg reduced the pain sensation in tail flick (p <0.01 and formalin test (p <0.001 in both phases. In paw edema test, NP 100 and 200 mg/kg significantly reduced the inflammation (p <0.01 and p <0.05.ConclusionThis study reveals that the essential oil of NP may minimize both the acute and chronic forms of nociception and may have potent role against inflammation, but the dose should be maintained precisely to obtain the intended effect.

  7. New Approaches to Clarify Antinociceptive and Anti-Inflammatory Effects of the Ethanol Extract from Vernonia condensata Leaves

    OpenAIRE

    Orlando Vieira de Sousa; Maria Silvana Alves; Pinho, José de Jesus R. G. De; Antônia Ribeiro; Carolina Miranda Gasparetto; Dalyara Mendonça de Matos; Felipe Valente Fernandes; Geórgia de Assis Dias Alves; Vanessa dos Santos Temponi; Jucélia Barbosa da Silva

    2011-01-01

    The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 5...

  8. Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor.

    Science.gov (United States)

    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 (Pnociceptive effect. 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.

  9. Antinociceptive effects of analgesic-antitumor peptide (AGAP, a neurotoxin from the scorpion Buthus martensii Karsch, on formalin-induced inflammatory pain through a mitogen-activated protein kinases-dependent mechanism in mice.

    Directory of Open Access Journals (Sweden)

    Qinghong Mao

    Full Text Available In the present study, we investigated the anti-nociceptive effect and the underlying mechanism of the analgesic-antitumor peptide (AGAP, a neurotoxin from the scorpion Buthus martensii Karsch. AGAP in doses of 0.2, 1 and 5 µg was injected intraplantarly (i.pl. before formalin injection 10 min at the same site. The suppression by intraplantar injection of AGAP on formalin-induced spontaneous nociceptive behaviors was investigated. The results show that AGAP could dose-dependently inhibit formalin-induced two-phase spontaneous flinching response. To investigate the mechanism of action of treatment with AGAP in inflammatory pain, the expressions of peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs including p-p38, p-ERK and p-JNK were examined. We found that formalin increased the expressions of peripheral and spinal MAPKs, which were prevented by pre-intraplantar injection of AGAP in inflammation pain model in mice. AGAP could also decrease the expression of spinal Fos induced by formalin. Furthermore, combinations the lower doses of the inhibitors of MAPKs (U0126, SP600125, or SB203580 0.1 µg with the lower dose of AGAP (0.2 µg, the results suggested that AGAP could potentiate the effects of the inhibitors of MAPKs on the inflammatory pain. The present results indicate that pre-intraplantar injection of AGAP prevents the inflammatory pain induced by formalin through a MAPKs-mediated mechanism in mice.

  10. Antinociceptive Effects of Analgesic-Antitumor Peptide (AGAP), a Neurotoxin from the Scorpion Buthus martensii Karsch, on Formalin-Induced Inflammatory Pain through a Mitogen-Activated Protein Kinases–Dependent Mechanism in Mice

    Science.gov (United States)

    Mao, Qinghong; Ruan, Jiaping; Cai, Xueting; Lu, Wuguang; Ye, Juan; Yang, Jie; Yang, Yang; Sun, Xiaoyan; Cao, Junli; Cao, Peng

    2013-01-01

    In the present study, we investigated the anti-nociceptive effect and the underlying mechanism of the analgesic-antitumor peptide (AGAP), a neurotoxin from the scorpion Buthus martensii Karsch. AGAP in doses of 0.2, 1 and 5 µg was injected intraplantarly (i.pl.) before formalin injection 10 min at the same site. The suppression by intraplantar injection of AGAP on formalin-induced spontaneous nociceptive behaviors was investigated. The results show that AGAP could dose-dependently inhibit formalin-induced two-phase spontaneous flinching response. To investigate the mechanism of action of treatment with AGAP in inflammatory pain, the expressions of peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, p-ERK and p-JNK were examined. We found that formalin increased the expressions of peripheral and spinal MAPKs, which were prevented by pre-intraplantar injection of AGAP in inflammation pain model in mice. AGAP could also decrease the expression of spinal Fos induced by formalin. Furthermore, combinations the lower doses of the inhibitors of MAPKs (U0126, SP600125, or SB203580 0.1 µg) with the lower dose of AGAP (0.2 µg), the results suggested that AGAP could potentiate the effects of the inhibitors of MAPKs on the inflammatory pain. The present results indicate that pre-intraplantar injection of AGAP prevents the inflammatory pain induced by formalin through a MAPKs-mediated mechanism in mice. PMID:24244296

  11. Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.

    Science.gov (United States)

    Montiel-Ruiz, Rosa Mariana; González-Trujano, María Eva; Déciga-Campos, Myrna

    2013-11-15

    In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Effect of restricted spinal motion on gait.

    Science.gov (United States)

    Konz, Regina; Fatone, Stefania; Gard, Steven

    2006-01-01

    Spinal orthoses are common in the treatment of various conditions that affect the spine. They encompass both the spine and pelvis and thus have implications for pelvic and lower-limb motion during walking in addition to a direct effect on spinal motion. The role of the spine in walking is largely ill-defined, and the consequences of restricted spinal motion on walking have yet to be explored. This study investigated the effect of spinal restriction on gait in able-bodied persons. Gait analyses were performed on 10 able-bodied subjects as they walked at five different speeds that were distributed across their comfortable range of speeds. Data were collected during walking with and without spinal restriction by a fiberglass body jacket, which is similar to a thoracolumbosacral orthosis (TLSO). With spinal restriction, peak-to-peak (PP) pelvic obliquity and rotation were significantly reduced across all walking speeds (p TLSO use or surgical restriction of spinal motion. An awareness of these issues will enable clinicians to monitor patients for problems that may result from decreased spine and pelvic motion.

  13. Anti-inflammatory, and antinociceptive effects of Campomanesia adamantium microencapsulated pulp

    Directory of Open Access Journals (Sweden)

    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.

  14. Electroacupuncture Pretreatment at GB20 Exerts Antinociceptive Effects via Peripheral and Central Serotonin Mechanism in Conscious Migraine Rats

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-01-01

    Full Text Available Background. While electroacupuncture (EA pretreatment in migraine has been found to attenuate pain and frequencies of attacks, the underlying mechanism of its antinociceptive effect remains poorly understood. Emerging evidence suggests that the serotonin system may be involved in migraine pathophysiology. Method. Forty male Sprague-Dawley rats were randomly assigned to Control, Model, EA, and sham acupuncture (SA groups. HomeCageScan was used to measure the effects on spontaneous nociceptive behaviors. Radioimmunoassay and high-performance liquid chromatography were used to evaluate the expression of 5-hydroxytryptamine (HT in the plasma and three-key structure of the descending pain modulatory system. Results. Our study showed that EA pretreatment could produce a significant reduction in resting, freezing, and grooming behavior and a significant increase in exploration behavior. Furthermore, we found that the level of 5-HT in plasma was significantly increased, and it was significantly decreased in the descending pain modulatory system in Model group. The aforementioned results were significantly reversed in EA group; that is, the level of 5-HT was increased in the rostroventromedial medulla (RVM and trigeminal nucleus caudalis (TNC region and decreased in the plasma. Conclusion. EA pretreatment exerts antinociceptive effects in a rat model of recurrent migraine, possibly via modulation of the serotonin system.

  15. Antinociceptive Effect of Morphine Microinjections into the Dorsal Hippocampus in the Formalin-Induced Orofacial Pain in Rats

    Directory of Open Access Journals (Sweden)

    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.

  16. Phytochemical screening, antinociceptive and anti-inflammatory effects of the essential oil of Myrcia pubiflora in mice

    Directory of Open Access Journals (Sweden)

    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.

  17. Involvement of Opioid System, TRPM8, and ASIC Receptors in Antinociceptive Effect of Arrabidaea brachypoda (DC Bureau

    Directory of Open Access Journals (Sweden)

    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.

  18. Antinociceptive Effect of Aqueous Extract of Origanum vulgare L. in Male Rats: Possible Involvement of the GABAergic System

    Science.gov (United States)

    Afarineshe Khaki, Mohammad Reza; Pahlavan, Yasamin; Sepehri, Gholamreza; Sheibani, Vahid; Pahlavan, Bahare

    2013-01-01

    The objective of the present investigation was to assess the possible involvement of GABAergic mechanism in analgesic effect of aqueous extract of Origanum Vulgare (ORG) in a rat model of acute pain test. Sixty-three anaesthetized male Wistar rats (200-250 g) were cannulated into the left ventricle. Five to seven days after the recovery from surgery, ORG extract was intraventricularly injected at dose of 3 μg/rat i.c.v. Then, baclofen (10 mg/Kg, IP), CGP35348 (100 nmol/Kg, i.c.v), muscimol (1 mg/Kg IP) and bicuculline (5 mg/Kg IP) were separately injected 20 min before the injection of ORG. The experimental groups were compared with intact (control) group (n = 7). The response latency of rats to thermal stimulation was recorded using Tail-Flick test. Injection of ORG extract resulted in a significant and dose-dependent increase in the response latency. There was also a significant increase in the response latency after co-administration of ORG extract with baclofen when compared with control group. However, following co-administration of ORG extract/bicuculline, a significant decrease in the response latency was observed compared to control group. In conclusion, the results of the present study suggest that aqueous extract of Origanum vulgare L. ssp. viridis possesses antinociceptive activity in a dose-dependent manner and ORG-induced antinociception might be mediated, at least in part, by both GABA receptors. PMID:24250616

  19. Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice.

    Science.gov (United States)

    Guo, T Z; Davies, M F; Kingery, W S; Patterson, A J; Limbird, L E; Maze, M

    1999-02-01

    Opiate receptors in the periaqueductal gray region and alpha2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2O and investigate which alpha2 adrenoceptor subtypes mediate this response. After obtaining institutional approval, antinociceptive dose-response and time-course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional alpha2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective alpha2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral alpha2-antagonist) and prazosin (alpha2B- and alpha2C-selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective alpha2 agonist, was tested in wild-type and transgenic mice. N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective alpha2B-/alpha2C-receptor antagonists but not by a central nervous system-impermeant alpha2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective alpha2B-/alpha2C-receptor antagonist. These data confirm that the antinociceptive response to an exogenous alpha2-agonist is mediated by an alpha2A adrenoceptor and that there appears to be a role for the alpha2B- or alpha2C

  20. Haeme oxygenase-1 overexpression via nAChRs and the transcription factor Nrf2 has antinociceptive effects in the formalin test.

    Science.gov (United States)

    Egea, Javier; Rosa, Angelo O; Lorrio, Silvia; del Barrio, Laura; Cuadrado, Antonio; López, Manuela G

    2009-11-01

    Epibatidine has shown antinociceptive effects in various pain models, being 200-fold more potent than morphine. Previous results from our laboratory demonstrated that HO-1 overexpression has an antinociceptive effect in the formalin test. Furthermore, epibatidine was able to induce haeme oxygenase-1 (HO-1). So, the aim of this study was to investigate the effect of HO-1 overexpression induced by epibatidine in nociception elicited by formalin injection in the mice hindpaw. Administration of epibatidine (4 microg/kg) 24h before the test reduced the nociceptive response during the first phase and second phase of the formalin test. This effect was prevented by treatment with tin protoporphyrin (SnPP, an inhibitor of HO-1 activity) administered via intraplantar 5min before the test, suggesting a main role of HO-1. Western blot analysis revealed that epibatidine treatment increased by 2-fold HO-1 expression in the paw; this effect was lost in knockout mice for nuclear factor-erythroid 2-related factor 2 (Nrf2) and was accompanied by the loss of its antinociceptive effect. Furthermore, the antinociceptive effect of epibatidine was related to the activation of alpha7 and/or alpha9 nAChRs since methyllycaconitine (MLA) and mecamylamine but not dihydro-beta-erythroidine (DHbetaE) reverted this effect. Finally, we showed by flow cytometry and by immunofluorescence that white blood cells of the animals injected with epibatidine expressed more HO-1 than control animals, and this expression was also reverted by MLA pre-treatment. These findings demonstrate that HO-1 induction by epibatidine has antinociceptive and anti-inflammatory effects by the activation of MLA-sensitive nAChRs.

  1. β‐Cyclodextrin‐complexed (−)‐linalool produces antinociceptive effect superior to that of (−)‐linalool in experimental pain protocols

    National Research Council Canada - National Science Library

    Quintans‐Júnior, Lucindo J; Barreto, Rosana S. S; Menezes, Paula P; Almeida, Jackson R. G. S; Viana, Ana Flávia S. C; Oliveira, Rita C. M; Oliveira, Aldeídia P; Gelain, Daniel P; Lucca Júnior, Waldecy; Araújo, Adriano A. S

    2013-01-01

    .... In this study, the antinociceptive effect of ( − )‐linalool and ( − )‐linalool/β‐ CD was examined using the acetic acid writhing reflex, formalin and hotplate tests in rodents. ( − )‐ L inalool and ( − )‐linalool/β...

  2. 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

    subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25...

  3. In vitro binding affinities of a series of flavonoids for μ-opioid receptors. Antinociceptive effect of the synthetic flavonoid 3,3-dibromoflavanone in mice.

    Science.gov (United States)

    Higgs, Josefina; Wasowski, Cristina; Loscalzo, Leonardo M; Marder, Mariel

    2013-09-01

    The pharmacotherapy for the treatment of pain is an active area of investigation. There are effective drugs to treat this problem, but there is also a need to find alternative treatments free of undesirable side effects. In the present work the capacity of a series of flavonoids to bind to the μ opioid receptor was evaluated. The most active compound, 3,3-dibromoflavanone (31), a synthetic flavonoid, presented a significant inhibition of the binding of the selective μ opioid ligand [(3)H]DAMGO, with a Ki of 0.846 ± 0.263 μM. Flavanone 31 was further synthesized using a simple and cheap procedure with good yield. Its in vivo effects in mice, after acute treatments, were studied using antinociceptive and behavioral assays. It showed no sedative, anxiolytic, motor incoordination effects or inhibition of the gastrointestinal transit in mice at the doses tested. It evidenced antinociceptive activity on the acetic acid-induced nociception, hot plate and formalin tests (at 10 mg/kg and 30 mg/kg). The results showed that the 5-HT2 receptor and the adrenoceptors seem unlikely to be involved in its antinociceptive effects. Naltrexone, a nonselective opioid receptors antagonist, totally blocked compound 31 antinociceptive effects on the hot plate test, but naltrindole (δ opioid antagonist) and nor-binaltorphimine (κ opioid antagonist) did not. These findings demonstrated that 3,3-dibromoflavanone (31), at doses that did not interfere with the motor performance, exerted clear dose dependent antinociception when assessed in the chemical and thermal models of nociception in mice and it seems that its action is related to the activation of the μ opioid receptor. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Höglund, A Urban

    2004-01-01

    and rilmenidine increased, while yohimbine decreased spinal acetylcholine release. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade attenuated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand......Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinal acetylcholine. The cholinergic receptor system interacts with several other receptor types, such as alpha2-adrenergic receptors. To fully understand these interactions, the effects...... of various receptor ligands on the cholinergic system must be investigated in detail. This study was initiated to investigate the effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine and the alpha2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors...

  5. Brain and spinal cord interaction: protective effects of exercise prior to spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Fernando Gomez-Pinilla

    Full Text Available We have investigated the effects of a spinal cord injury on the brain and spinal cord, and whether exercise provided before the injury could organize a protective reaction across the neuroaxis. Animals were exposed to 21 days of voluntary exercise, followed by a full spinal transection (T7-T9 and sacrificed two days later. Here we show that the effects of spinal cord injury go beyond the spinal cord itself and influence the molecular substrates of synaptic plasticity and learning in the brain. The injury reduced BDNF levels in the hippocampus in conjunction with the activated forms of p-synapsin I, p-CREB and p-CaMK II, while exercise prior to injury prevented these reductions. Similar effects of the injury were observed in the lumbar enlargement region of the spinal cord, where exercise prevented the reductions in BDNF, and p-CREB. Furthermore, the response of the hippocampus to the spinal lesion appeared to be coordinated to that of the spinal cord, as evidenced by corresponding injury-related changes in BDNF levels in the brain and spinal cord. These results provide an indication for the increased vulnerability of brain centers after spinal cord injury. These findings also imply that the level of chronic activity prior to a spinal cord injury could determine the level of sensory-motor and cognitive recovery following the injury. In particular, exercise prior to the injury onset appears to foster protective mechanisms in the brain and spinal cord.

  6. Pregabalin enhances the antinociceptive effect of oxycodone and morphine in thermal models of nociception in the rat without any pharmacokinetic interactions.

    Science.gov (United States)

    Jokinen, V; Lilius, T O; Laitila, J; Niemi, M; Rauhala, P V; Kalso, E A

    2016-02-01

    Oxycodone is increasingly being used in combination with pregabalin. Pregabalin use is prevalent in opioid-dependent individuals. A high number of deaths caused by the co-use of gabapentinoids and opioids occur. It is not known whether pregabalin affects concentrations of oxycodone or morphine in the central nervous system. Effects of pregabalin on acute oxycodone or morphine-induced antinociception, tolerance and sedation were studied using tail-flick, hot plate and rotarod tests in male Sprague-Dawley rats. Concentrations of pregabalin, opioids and their major metabolites in the brain were quantified by mass spectrometry. In the hot plate test, morphine (2.5 mg/kg, s.c.) caused antinociception of 28% maximum possible effect (MPE), whereas pregabalin (50 mg/kg, i.p.) produced 8-10% MPE. Co-administration of pregabalin and morphine resulted in antinociception of 63% MPE. Oxycodone (0.6 mg/kg s.c.) produced antinociception of 18% MPE, which increased to 39% MPE after co-administration with pregabalin. When pregabalin 10 mg/kg was administered before oxycodone (0.6 mg/kg, s.c.) or morphine (2.5 mg/kg), only the effect of oxycodone was potentiated in the tail-flick and the hot plate tests. Brain concentrations of the opioids, their major metabolites and pregabalin were unchanged. Pregabalin co-administration (50 mg/kg, i.p., once daily) did not prevent the development of morphine tolerance. Pregabalin potentiated antinociceptive and sedative effects of oxycodone and morphine in acute nociception. Co-administration of pregabalin with the opioids did not affect the brain concentrations of oxycodone or morphine. Pregabalin did not prevent morphine tolerance. © 2015 European Pain Federation - EFIC®

  7. Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents.

    Directory of Open Access Journals (Sweden)

    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.

  8. Citral: a monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain.

    Science.gov (United States)

    Nishijima, Catarine M; Ganev, Ellen G; Mazzardo-Martins, Leidiane; Martins, Daniel F; Rocha, Lúcia R M; Santos, Adair R S; Hiruma-Lima, Clelia A

    2014-08-05

    Citral (3,7-dimethyl-2,6-octadienal) is an open-chain monoterpenoid present in the essential oils of several medicinal plants. The aim of this work was to evaluate the effects of orally administered citral in experimental models of acute and chronic nociception, inflammation, and gastric ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs). Oral treatment with citral significantly inhibited the neurogenic and inflammatory pain responses induced by intra-plantar injection of formalin. Citral also had prophylactic and therapeutic anti-nociceptive effects against mechanical hyperalgesia in plantar incision surgery, chronic regional pain syndrome, and partial ligation of sciatic nerve models, without producing any significant motor dysfunction. In addition, citral markedly attenuated the pain response induced by intra-plantar injection of glutamate and phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator), as well as by intrathecal (i.t.) injection of ionotropic and metabotropic glutamate receptor agonists (N-methyl-D-aspartic acid [NMDA] and 1-amino-1,3-dicarboxycyclopentane [trans-ACPD], respectively), substance P, and cytokine tumour necrosis factor-α. However, citral potentiated behaviours indicative of pain caused by i.t., but not intra-plantar, injection of a transient receptor potential vanilloid receptor type 1 (TRPV1) agonist. Finally, the anti-nociceptive action of citral was found to involve significant activation of the 5-HT2A serotonin receptor. The effect of citral was accompanied by a gastro-protective effect against NSAID-induced ulcers. Together, these results show the potential of citral as a new drug for the treatment of pain. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Erfanparast, Amir; Taati, Mina; Dabbaghi, Milad

    2014-01-01

    Calcium, through its various channels involves in local, spinal and supra-spinal transmission of pain. In the present study, we investigated the separate and combined treatment effects of verapamil (a calcium channel blocker), morphine (an opioid agonist) and naloxone (an opioid antagonist) on pain in the orofacial region of rats. Orofacial pain was induced by subcutaneous (SC) injection of formalin (50 µL, 1.5%) into the left upper lip side, and the time durations spent face rubbing with epsilateral forepaw were recorded in three min blocks for a period of 45 min. Formalin induced a biphasic pattern (first phase: 0-3 min; second phase: 15-33 min) of pain. Intraperitoneal (IP) injections of verapamil (2 and 8 mg kg(-1)) and morphine (2 and 4 mg kg(-1)) suppressed orofacial pain. Co-administration of sub-analgesic doses of verapamil (0.5 mg kg(-1)) and morphine (1 mg kg(-1)) produced second phase analgesia. Both phases of formalin-induced pain were suppressed when an analgesic dose (2 mg kg(-1)) of verapamil co-administered with a sub-analgesic dose (1 mg kg(-1)) of morphine. The SC injection of naloxone (2 mg kg(-1)) alone with no effect on pain intensity, prevented the antinociceptive effects induced by morphine (2 mg kg(-1)), but not verapamil (2 mg kg(-1)). The obtained results showed antinociceptive effects for verapamli and morphine on orofacial pain. Co-administrations of verapamil and morphine produced antinociceptive effects. It seems that opioid analgesic system may not have a role in the verapamil-induced antinociception.

  10. Antinociceptive and toxic effects of (+)-epibatidine oxalate attributable to nicotinic agonist activity.

    Science.gov (United States)

    Rupniak, N M; Patel, S; Marwood, R; Webb, J; Traynor, J R; Elliott, J; Freedman, S B; Fletcher, S R; Hill, R G

    1994-12-01

    1. Epibatidine is an analgesic substance, isolated from the skin of the poisonous frog Epipedobates tricolor, for which the mechanism of action was previously unknown. 2. The IC50 of synthetic (+)-epibatidine oxalate (the naturally occurring isomer) for [3H]-nicotine binding to rat whole-brain membranes was 0.1 nM. The (-)-isomer also exhibited high affinity (IC50 = 0.2 nM). 3. (+)- and (-)-Epibatidine exhibited much lower affinity for displacement of the muscarinic ligand [3H]-N-methylscopolamine binding to rat cortical membranes (Kapp = 6.9 microM and 16.0 microM respectively). The (+)-enantiomer of epibatidine had an antagonist/agonist (NMS/oxo-M) binding ratio of 4.2 This is consistent with a muscarinic antagonist profile. 4. (+)-Epibatidine oxalate (10 microM) did not cause significant (> 30%) displacement of radioligand binding to opioid, excitatory amino acid, benzodiazepine, 5-HT, dopamine, adrenaline or peptide receptors. 5. (+)- and (-)-Epibatidine (5-20 micrograms kg-1 s.c.) doubled response latency in the mouse hot-plate test. Antinociception and behavioural depression induced by (+)-epibatidine (5 micrograms kg-1) was fully blocked by the nicotinic antagonists mecamylamine (2 mg kg-1 s.c.) or dihydro-beta-erythroidine (2 mg kg-1 s.c.). The muscarinic antagonist scopolamine (0.4 and 10 mg kg-1 s.c.) caused partial reversal of antinociception induced by (+)-epibatidine in mice, but not in rats. 6. These findings demonstrate that (+)-epibatidine oxalate salt is a highly selective and potent nicotinic analgesic agent.

  11. Antinociceptive effects of mixtures of mu opioid receptor agonists and cannabinoid receptor agonists in rats: impact of drug and fixed-dose ratio.

    Science.gov (United States)

    Maguire, David R; France, Charles P

    2017-11-25

    Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists). Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments. The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Δ9-THC and CP55940 were studied in male Sprague-Dawley rats (n=16) using a warm water tail withdrawal procedure. The ratio of opioid to cannabinoid (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Δ9-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture. The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain. Copyright © 2017. Published by Elsevier B.V.

  12. Adrenergic Component of Nicotine Antinociception in Rats | Ibironke ...

    African Journals Online (AJOL)

    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 investigated . The present study examined the effects of two adrenergic receptor antagonists , propranolol and prazosin .on nicotine antinociception using ...

  13. Intra-periaqueductal grey microinjections of an imidazo[1,2-b]pyridazine derivative, DM2, affects rostral ventromedial medulla cell activity and shows antinociceptive effect.

    Science.gov (United States)

    Palazzo, Enza; Rimoli, Maria Grazia; De Chiaro, Maria; Guida, Francesca; Melisi, Daniela; Curcio, Annalisa; de Novellis, Vito; Marabese, Ida; Rossi, Francesco; Abignente, Enrico; Maione, Sabatino

    2010-03-01

    The 6-methoxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acid, DM2, exerts anti-absence activity and blocks Cav3.1 channel, a T-type voltage-dependent Ca(2+) channel subtype, in vitro. The current study investigated the effect of intra-ventrolateral periaqueductal grey (VLPAG) administration of DM2 on formalin-induced nocifensive responses in rats. In addition, the effect of intra-VLPAG microinjection of DM2 on the ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) cell population was also investigated. Formalin was injected subcutaneously into the dorsal surface of the hind paws of awake rats. We found that DM2 reduced nocifensive responses in the late phase of the formalin test. Moreover, in the RVM, the intra-VLPAG microinjection of DM2 reduced the ongoing and tail flick-related activity of the nociceptive ON cells, whereas it increased the ongoing activity and reduced the tail flick-induced pause of the antinociceptive OFF cells, consistent with antinociception. Behavioural and electrophysiological effects were reproduced by intra-VLPAG microinjection of ethosuximide, a conventional T-type Ca(2+) channel blocker. Finally, DM2 administration did not produce any adverse cardiovascular effects as blood pressure and heart rate remained unchanged. In conclusion, DM2 plays an analgesic role in vivo and changes RVM cell activity, consistent with antinociception. These effects were even more potent than those elicited by ethosuximide treatments. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  15. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa.

    Science.gov (United States)

    Matsumoto, Kenjiro; Horie, Syunji; Ishikawa, Hayato; Takayama, Hiromitsu; Aimi, Norio; Ponglux, Dhavadee; Watanabe, Kazuo

    2004-03-12

    Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for micro-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.

  16. A Comparative Analysis of the Chemical Composition, Anti-Inflammatory, and Antinociceptive Effects of the Essential Oils from Three Species of Mentha Cultivated in Romania

    Directory of Open Access Journals (Sweden)

    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.

  17. The effect of spinal manipulative therapy on spinal range of motion

    DEFF Research Database (Denmark)

    Millan, Mario; Leboeuf-Yde, Charlotte; Budgell, Brian

    2012-01-01

    Spinal manipulative therapy (SMT) has been shown to have an effect on spine-related pain, both clinically and in experimentally induced pain. However, it is unclear if it has an immediate noticeable biomechanical effect on spinal motion that can be measured in terms of an increased range of motion...

  18. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

    Science.gov (United States)

    Chen, Jun; Lariviere, William R.

    2010-01-01

    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. PMID:20558236

  19. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    Science.gov (United States)

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  20. Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

    Science.gov (United States)

    2012-01-01

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

  1. Antinociceptive properties and acute toxicity of ethanol extract of ...

    African Journals Online (AJOL)

    The antinociceptive effect of ethanol extract (Bl-EtOH) in mice was carried out using chemical (writhing and formalin) and thermal (hot plate) models of nociception. ... Naloxone (1.5 mg/kg, i.p.) antagonized the antinociceptive action of Bl-EtOH (100 mg/kg), and this finding suggests involvement of opioid mechanism.

  2. Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).

    Science.gov (United States)

    Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

    2014-03-01

    Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  3. Antiinflammatory, antinociceptive and antipyretic effects of hydroethanolic extract from Macrosiphonia velame (A. St.-Hil. M. Arg. in animal models

    Directory of Open Access Journals (Sweden)

    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

  4. Antinociceptive effect of hydroalcoholic extract and isoflavone isolated from Polygala molluginifolia in mice: evidence for the involvement of opioid receptors and TRPV1 and TRPA1 channels.

    Science.gov (United States)

    Nucci-Martins, Catharina; Nascimento, Leandro F; Venzke, Dalila; Brethanha, Lizandra C; Sako, Alysson V F; Oliveira, Aldo S; Brighente, Inês M C; Micke, Gustavo A; Pizzolatti, Moacir G; Santos, Adair R S

    2016-05-15

    The plants of the genus Polygala (Polygalaceae) have been used for a long time in folk medicine to treat pain and inflammation. The species Polygala molluginifolia is native to southern Brazil and is popularly known as "cânfora". The presented study analyzes the antinociceptive effect of hydroalcoholic extract from Polygala molluginifolia (HEPm) and an isoflavone (ISO) isolated from the extract, in behavioral models of pain in mice, as well as the mechanism underlying this effect. The phytochemical analysis of HEPm was performed through a capillary electrophoresis analysis and colorimetric test. The antinociceptive effects of HEPm and ISO (10-1000 mg/kg, i.g.) were evaluated by applying the formalin test; mechanical and thermal hyperalgesia to postoperative pain in mice. The possible involvement of opioid receptors, TRPV1 and TRPA1 channels in the antinociceptive effect of HEPm and ISO were also evaluated. Finally, the nonspecific effects of HEPm and ISO were evaluated by measuring locomotor activity (Open-field Test) and corporal temperature. The 5,3',4'-trihydroxy-6″,6″-dimethylpyrano[2″,3″:7,6] isoflavone (ISO) was identified in HEPm by capillary electrophoresis analysis and selected for the experimental tests. The oral administration of HEPm or of ISO significantly inhibited the neurogenic and inflammatory phases of formalin-induced pain, edema formation and local hyperemia, without causing any change to locomotor activity. Acute and repeated treatment of animals with HEPm reduced mechanical and thermal (heat and cold) hyperalgesia in the postoperative pain. In addition, administering HEPm or ISO markedly reduced nociceptive behavior induced by the peripheral and central injection of TRPV1 and TRPA1 channels activators. Finally, the antinociception provided by the administration of HEPm or ISO was reversed by the preadministration of naloxone. Taken together, these results provide the first experimental evidence of the significant antinociceptive

  5. Venlafaxine and oxycodone have different effects on spinal and supra-spinal activity in Man

    DEFF Research Database (Denmark)

    Lelic, Dina; Valeriani, Massimiliano; Fischer, Iben W D

    2017-01-01

    five days of treatment. Assessment of central effects of the three treatments involved: 1) amplitudes and latencies of spinal EPs (spinal level), 2) amplitudes and latencies of the P14 potential (subcortical level), 3) amplitudes and latencies of early and late cortical EPs (cortical level), 4) brain...

  6. Antioxidant, anti-inflammatory and anti-nociceptive effects of Ammannia baccifera L. (Lythracceae), a folklore medicinal plant.

    Science.gov (United States)

    Loganayaki, Nataraj; Siddhuraju, Perumal; Manian, Sellamuthu

    2012-03-27

    Ammannia baccifera L. has been reported as folklore remedy for the treatment of inflammation and tumor in the state of Rajasthan, India. The present study was designed to investigate the antioxidant, anti-inflammatory and anti-nociceptive effects of the methanol extract from the aerial parts of Ammannia baccifera under in vitro and in vivo models. The in vitro antioxidant activity of the extract was measured using DPPH, superoxide, hydroxyl and nitric oxide radicals. The anti-inflammatory activity was evaluated using carrageenan induced paw edema. Analgesic activity of the methanol extract was estimated against acetic acid-induced writhing and hot plate methods. The IC(50) value for free radical scavenging activity of this extract was significantly superior over the positive standards butylated hydroxyl anisole (BHA) and rutin. The extract exhibited significant anti-inflammatory and analgesic activities at the dose of 100 and 200mg/kg p.o. The analgesic effect of the higher dose of the extract (200mg/kg) was comparable with the standard drugs aspirin and morphine. The present study scientifically validated the traditional use of this plant against inflammation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    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.

  8. Antinociceptive effects of an extract, fraction and an isolated compound of the stem bark of Maytenus rigida

    Directory of Open Access Journals (Sweden)

    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.

  9. Antinociceptive effects of an extract, fraction and an isolated compound of the stem bark of Maytenus rigida

    Directory of Open Access Journals (Sweden)

    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.

  10. Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

    Science.gov (United States)

    Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2016-06-15

    Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Evaluation of the Antinociceptive Effect of Hydroalcoholic Extract of Potentilla Reptans L. in the Adult Male Rat

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    M Mahmoodi

    2016-06-01

    Full Text Available Introduction: Medicinal plants have been a focus of attention to researchers due to their fewer side effects in treating diseases comared to chemical drugs. Some health properties of medicinal plants such as anti-hypercholesterolemia and antioxidant effects of Potentilla reptans have been proven. Therefore, the present study aimed to investigate the antinociceptive and analgesic effect of hydro-alcoholic extract of Potentilla reptans L. (HEP in the male rat. Methods: In this experimental study, 36 male rats were divided into 6 groups, including: control group (normal saline, morphine group (1mg/kg, HEP groups (treated with 25, 50 and 100 mg/kg, and naloxone group (200 mg/kg. Writhing, formalin and tail-flick tests were used to evaluate the analgesic effects of the extract. In order to analyze the study data, variance and Tukey test were applied. Results: The results of the present study demonstrated that in writhing test (P<0.05 and P<0.001 respectively, formalin test (P<0.05, P<0.001 and tail-flick test (P<0.05, P<0.01; the injection of 50, and 100mg/kg dose of the extract produced significant analgesic effects compared with the control group.  50mg/kg dose of Naloxone injection extract has shown a significant analgesic effect in the formalin test (P<0.05. In addition, the effect of the analgesic dose of 100mg/kg of the extract in formalin test was similar to that of morphine. Conclusions: The findings of the current study revealed that Potentilla reptans L. (HEP has a significant analgesic effect. Opioid pathway seems to be one of the possible mechanisms of extract effects, which further clinical trials are recommended  in this case.

  12. 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.

  13. The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice.

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    Donvito, Giulia; Bagdas, Deniz; Toma, Wisam; Rahimpour, Elnaz; Jackson, Asti; Meade, Julie A; AlSharari, Shakir; Kulkarni, Abhijit R; Ivy Carroll, F; Lichtman, Aron H; Papke, Roger L; Thakur, Ganesh A; Imad Damaj, M

    2017-09-01

    Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca2+-dependent manner. Here, we investigated potential crosstalk between α7 nAChR and PPAR-α, using the formalin test, a mouse model of tonic pain. Using pharmacological and genetic approaches, we found that PNU282987, a full α7 agonist, attenuated formalin-induced nociceptive behavior in α7-dependent manner. Interestingly, the selective PPAR-α antagonist GW6471 blocked the antinociceptive effects of PNU282987, but did not alter the antinociceptive responses evoked by the α7 nAChR PAM PNU120596, ago-PAM GAT107, and silent agonist NS6740. Moreover, GW6471 administered systemically or spinally, but not via the intraplantar surface of the formalin-injected paw blocked PNU282987-induced antinociception. Conversely, exogenous administration of the naturally occurring PPAR-α agonist PEA potentiated the antinociceptive effects of PNU282987. In contrast, the cannabinoid CB1 antagonist rimonabant and the CB2 antagonist SR144528 failed to reverse the antinociceptive effects of PNU282987. These findings suggest that PPAR-α plays a key role in a putative antinociceptive α7 nicotinic signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Paradoxical effect of noradrenaline-mediated neurotransmission in the antinociceptive phenomenon that accompanies tonic-clonic seizures: role of locus coeruleus neurons and α(2)- and β-noradrenergic receptors.

    Science.gov (United States)

    Felippotti, Tatiana Tocchini; dos Reis Ferreira, Célio Marcos; de Freitas, Renato Leonardo; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Paschoalin-Maurin, Tatiana; Coimbra, Norberto Cysne

    2011-10-01

    The postictal state is generally followed by antinociception. It is known that connections between the dorsal raphe nucleus, the periaqueductal gray matter, and the locus coeruleus, an important noradrenergic brainstem nucleus, are involved in the descending control of ascending nociceptive pathways. The aim of the present study was to determine whether noradrenergic mechanisms in the locus coeruleus are involved in postictal antinociception. Yohimbine (an α(2)-receptor antagonist) or propranolol (a β-receptor antagonist) was microinjected unilaterally into the locus coeruleus, followed by intraperitoneal administration of pentylenetetrazole (PTZ), a noncompetitive antagonist that blocks GABA-mediated Cl(-) influx. Although the administration of both yohimbine and propranolol to the locus coeruleus/subcoeruleus area resulted in a significant decrease in tonic or tonic-clonic seizure-induced antinociception, the effect of yohimbine restricted to the locus coeruleus was more distinct compared with that of propranolol, possibly because of the presynaptic localization of α(2)-noradrenergic receptors in locus coeruleus neurons. These effects were related to the modulation of noradrenergic activity in the locus coeruleus. Interestingly, microinjections of noradrenaline into the locus coeruleus also decrease the postictal antinociception. The present results suggest that the mechanism underlying postictal antinociception involves both α(2)- and β-noradrenergic receptors in the locus coeruleus, although the action of noradrenaline on these receptors causes a paradoxical effect, depending on the nature of the local neurotransmission. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Sedative and antinociceptive effects of romifidine and xylazine in Thoroughbred mares Efeito sedativo e antinociceptivo da romifidina e xilazina em éguas Puro Sangue Inglês

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    F.G. Christovão

    2006-12-01

    Full Text Available The sedative and antinociceptive effects of romifidine (0.1mg/kg and of xylazine (1.0mg/kg on Thoroughbred mares were studied. Sedation was evaluated by quantifying spontaneous locomotor activity (SLA and head height (HH in animals placed in automated individual behaviour stalls. Antinociception was determined utilizing a heat irradiation lamp recording the latency time for the hoof withdrawal reflex (HWRL and the latency time for the skin twitch reflex (STRL in a randomised block design with 10 replicates. Comparison of the sedative effects of romifidine and of xylazine on SLA showed a faster effect for xylazine. Regarding the sedative effect of the substances based on HH, romifidine caused a longer-lasting effect. Romifidine caused an increase in HWRL and STRL, and xylazine, an agent known for its analgesic effect, did not have an antinociceptive effect based on STRL result. The antinociceptive effect of romifidine was more pronounced than the xylazine effect.Compararam-se os efeitos sedativos e antinociceptivos da romifidina (0,1mg/kg e da xilazina (1,0mg/kg em éguas da raça Puro Sangue Inglês. A sedação foi quantificada por meio da atividade locomotora espontânea (ALE e altura da cabeça (AC em baias individuais automatizadas para o estudo do comportamento. A antinocicepção foi avaliada utilizando uma lâmpada de irradiação de calor registrando-se a latência para o reflexo de retirada do membro (LRRM e a latência para o reflexo do frêmito cutâneo (LRFC, em delineamento experimental em blocos ao acaso com 10 repetições. O efeito sedativo sobre a ALE foi de aparecimento mais rápido no grupo exposto à xilazina, ao passo que a ptose da cabeça foi mais prolongada no grupo que recebeu romifidina. A romifidina promoveu aumento da LRRM e LRFC e a xilazina não causou efeito antinociceptivo medido pela LRFC. O efeito antinociceptivo da romifidina foi mais pronunciado que o da xilazina.

  16. Antinociceptive, anti-inflammatory and gastroprotective effects of a hydroalcoholic extract from the leaves of Eugenia punicifolia (Kunth) DC. in rodents.

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    Basting, Rosanna T; Nishijima, Catarine M; Lopes, Juliana A; Santos, Raquel C; Lucena Périco, Larissa; Laufer, Stefan; Bauer, Silke; Costa, Miriam F; Santos, Lourdes C; Rocha, Lúcia R M; Vilegas, Wagner; Santos, Adair R S; Dos Santos, Catarina; Hiruma-Lima, Clélia A

    2014-11-18

    An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation. The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents. The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP. The oral administration of HEEP (125, 250 and 500mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l-arginine (500mg/kg, i.p.) but not by naloxone (1mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3-30mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500mg/kg, p.o.) protected the rats against ethanol (88.4-99.8%) and indomethacin (53-72.3%) and increased the mucus levels

  17. Redox-Dependent Modulation of T-Type Ca2+ Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P

    Science.gov (United States)

    Huang, Dongyang; Huang, Sha; Gao, Haixia; Liu, Yani; Qi, Jinlong; Chen, Pingping; Wang, Caixue; Scragg, Jason L.; Vakurov, Alexander; Peers, Chris; Du, Xiaona

    2016-01-01

    Abstract Aims: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. Results: SP acutely inhibited T-type voltage-gated Ca2+ channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca2+ channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K+ channels described earlier. Innovation: Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca2+ current and concurrent enhancement of anti-algesic M-type K+ current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. Conclusion: SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233–251. PMID:27306612

  18. Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.

    Science.gov (United States)

    Huang, Dongyang; Huang, Sha; Gao, Haixia; Liu, Yani; Qi, Jinlong; Chen, Pingping; Wang, Caixue; Scragg, Jason L; Vakurov, Alexander; Peers, Chris; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

    2016-08-10

    Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca(2+) channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K(+) channels described earlier. Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca(2+) current and concurrent enhancement of anti-algesic M-type K(+) current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233-251.

  19. The Antinociceptive Effects of JWH-015 in Chronic Inflammatory Pain Are Produced by Nitric Oxide-cGMP-PKG-KATP Pathway Activation Mediated by Opioids

    Science.gov (United States)

    Negrete, Roger; Hervera, Arnau; Leánez, Sergi; Martín-Campos, Jesús M.; Pol, Olga

    2011-01-01

    Background Cannabinoid 2 receptor (CB2R) agonists attenuate inflammatory pain but the precise mechanism implicated in these effects is not completely elucidated. We investigated if the peripheral nitric oxide-cGMP-protein kinase G (PKG)-ATP-sensitive K+ (KATP) channels signaling pathway triggered by the neuronal nitric oxide synthase (NOS1) and modulated by opioids, participates in the local antinociceptive effects produced by a CB2R agonist (JWH-015) during chronic inflammatory pain. Methodology/Principal Findings In wild type (WT) and NOS1 knockout (NOS1-KO) mice, at 10 days after the subplantar administration of complete Freund's adjuvant (CFA), we evaluated the antiallodynic (von Frey filaments) and antihyperalgesic (plantar test) effects produced by the subplantar administration of JWH-015 and the reversion of their effects by the local co-administration with CB2R (AM630), peripheral opioid receptor (naloxone methiodide, NX-ME) or CB1R (AM251) antagonists. Expression of CB2R and NOS1 as well as the antinociceptive effects produced by a high dose of JWH-015 combined with different doses of selective L-guanylate cyclase (ODQ) or PKG (Rp-8-pCPT-cGMPs) inhibitors or a KATP channel blocker (glibenclamide), were also assessed. Results show that the local administration of JWH-015 dose-dependently inhibited the mechanical and thermal hypersensitivity induced by CFA which effects were completely reversed by the local co-administration of AM630 or NX-ME, but not AM251. Inflammatory pain increased the paw expression of CB2R and the dorsal root ganglia transcription of NOS1. Moreover, the antinociceptive effects of JWH-015 were absent in NOS1-KO mice and diminished by their co-administration with ODQ, Rp-8-pCPT-cGMPs or glibenclamide. Conclusions/Significance These data indicate that the peripheral antinociceptive effects of JWH-015 during chronic inflammatory pain are mainly produced by the local activation of the nitric oxide-cGMP-PKG-KATP signaling pathway, triggered

  20. The antinociceptive effects of JWH-015 in chronic inflammatory pain are produced by nitric oxide-cGMP-PKG-KATP pathway activation mediated by opioids.

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    Roger Negrete

    Full Text Available BACKGROUND: Cannabinoid 2 receptor (CB2R agonists attenuate inflammatory pain but the precise mechanism implicated in these effects is not completely elucidated. We investigated if the peripheral nitric oxide-cGMP-protein kinase G (PKG-ATP-sensitive K(+ (KATP channels signaling pathway triggered by the neuronal nitric oxide synthase (NOS1 and modulated by opioids, participates in the local antinociceptive effects produced by a CB2R agonist (JWH-015 during chronic inflammatory pain. METHODOLOGY/PRINCIPAL FINDINGS: In wild type (WT and NOS1 knockout (NOS1-KO mice, at 10 days after the subplantar administration of complete Freund's adjuvant (CFA, we evaluated the antiallodynic (von Frey filaments and antihyperalgesic (plantar test effects produced by the subplantar administration of JWH-015 and the reversion of their effects by the local co-administration with CB2R (AM630, peripheral opioid receptor (naloxone methiodide, NX-ME or CB1R (AM251 antagonists. Expression of CB2R and NOS1 as well as the antinociceptive effects produced by a high dose of JWH-015 combined with different doses of selective L-guanylate cyclase (ODQ or PKG (Rp-8-pCPT-cGMPs inhibitors or a KATP channel blocker (glibenclamide, were also assessed. Results show that the local administration of JWH-015 dose-dependently inhibited the mechanical and thermal hypersensitivity induced by CFA which effects were completely reversed by the local co-administration of AM630 or NX-ME, but not AM251. Inflammatory pain increased the paw expression of CB2R and the dorsal root ganglia transcription of NOS1. Moreover, the antinociceptive effects of JWH-015 were absent in NOS1-KO mice and diminished by their co-administration with ODQ, Rp-8-pCPT-cGMPs or glibenclamide. CONCLUSIONS/SIGNIFICANCE: These data indicate that the peripheral antinociceptive effects of JWH-015 during chronic inflammatory pain are mainly produced by the local activation of the nitric oxide-cGMP-PKG-KATP signaling pathway

  1. Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain.

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    David A Barrière

    Full Text Available The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404 and that this metabolite contributes to paracetamol's antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA, both of which may undergo a fatty acid amide hydrolase (FAAH-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl-9Z-octadecenamide (HPODA and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol's analgesic activity via

  2. Anti-nociceptive and anti-inflammatory effects of Withania somnifera root in fructose fed male rats.

    Science.gov (United States)

    Shahraki, Mohammad Reza; Samadi Noshahr, Zahra; Ahmadvand, Hassan; Nakhaie, Alireza

    2016-06-01

    Insulin resistance is a metabolic disorder which affects the diabetes mellitus pathophysiology and alters the cell excitability. This study has been designed to evaluate the anti-nociceptive and anti-inflammatory effects of chronic administration of Withania somnifera root (WSR) in fructose drinking water rats. An experiment was carried out on 48 Wistar-Albino male rats, weighting 200±30 g, which were divided into six groups (n=8): control group (C), control morphine (CM), W. somnifera group (WS) which received WSR (62.5 mg/g diet), W. somnifera naloxone group (WSN) which received WSR and naloxone, fructose (F) group which received fructose drinking water and FWS group which received fructose-enriched drinking water and WSR during the trial period. A biphasic pain response was induced after intraplantar injection of formalin (50 μL, 1%). Pain behavior was measured using Dubuisson methods. The obtained data were analyzed by SPSS software V. 18, using ANOVA and Tukey test. Results were expressed as mean±SD. Statistical differences were considered significant at p<0.05. The results showed that the insulin resistance index, blood sugar, insulin, IL-6, TNF-α, and acute and chronic pain score in the F group were significantly increased in comparison with the control group, but these parameters in the FWS group were significantly decreased compared with the F group (p<0.001). Our findings indicated that chronic oral administration of WSR has analgesic and anti-inflammatory effects in fructose drinking water rats and causes improved insulin resistance index.

  3. Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors.

    Science.gov (United States)

    Fichna, Jakub; Dicay, Michael; Lewellyn, Kevin; Janecka, Anna; Zjawiony, Jordan K; MacNaughton, Wallace K; Storr, Martin A

    2012-06-01

    Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  4. Antinociceptive effects of a new sigma-1 receptor antagonist (N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy)acetamide) in two types of nociception.

    Science.gov (United States)

    García-Martínez, Betzabeth Anali; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; Navarrete-Vázquez, Gabriel; Melo-Hernández, Luis Alberto; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Schepmann, Dirk; Wünsch, Bernhard; López-Muñoz, Francisco Javier

    2016-01-15

    Pain has become an active clinical challenge due its etiological heterogeneity, symptoms and mechanisms of action. In the search for new pharmacological therapeutic alternatives, sigma receptors have been proposed as drug targets. This family consists of sigma-1 and sigma-2 receptors. The sigma-1 system is involved in nociception through its chaperone activity. Additionally, it has been shown that agonist to these receptors promote related sensitisation and pain hypersensitisation, suggesting the possible use of antagonists for sigma-1 receptors as an alternative therapy. The aim of this study was to evaluate the antinociceptive effect of a new sigma-1 receptor antagonist N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy)acetamida (NMIN) in two types of pain (arthritic and neuropathic) and to compare its efficacy and potency with reference drugs. The antinociceptive effects of NMIN were quantitatively evaluated using the pain-induced functional impairment model in the rat and the acetone test in a rat model of neuropathic pain. NMIN (sigma-1 receptor affinity of 324nM) did not show any antinociceptive activity in the arthritic pain model but showed a dose-dependent anti-allodynic effect in neuropathic pain. NMIN showed a similar efficacy compared to the effects obtained with morphine and the sigma-1 antagonist BD-1063. However, these reference drugs showed increased potency compared with NMIN. Our results suggest that sigma-1 receptors may play an important direct role in neuropathic pain but not in arthritic pain, supporting the hypothesis that NMIN may be useful for the treatment of neuropathic pain. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The Posterior Hypothalamus Exerts Opposing Effects on Nociception via the A7 Catecholamine Cell Group in Rat

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    Jeong, Younhee; Moes, Jesse R.; Wagner, Monica

    2012-01-01

    Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125 nmol) produced antinociception that was blocked by pretreatment with atropine sulfate. Intrathecal injection of the α2-adrenoceptor antagonist yohimbine reversed PH-induced antinociception, but the α1-adrenoceptor antagonist WB4101 facilitated antinociception. Intrathecal injection of normal saline had no effect. In a separate experiment, cobalt chloride, which reversibly arrests synaptic activity, was microinjected into the A7 cell group and blocked PH-induced antinociception. These findings provide evidence that the PH modulates nociception in part through connections with the A7 catecholamine cell group through opposing effects. Antinociception occurs from actions at α2-adrenoceptors in the dorsal horn, while concurrent hyperalgesia occurs from actions of norepinephrine at α1-adrenoceptors. This hyperalgesic response likely attenuates antinociception from PH stimulation. PMID:23036619

  6. Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

    Directory of Open Access Journals (Sweden)

    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.

  7. Antinociceptive potentiation of pethidine (demerol) by clomipramine ...

    African Journals Online (AJOL)

    ... late phase of formalin test compared to the vehicle treated animals. The combination of pethidine 5mg / kg and clomipramine 0.75mg / kg caused a highly significant antinociceptive effect (P<0.01) in the late phase of formalin test. Conclusion: This study demonstrates a marked reduction in the time spent in pain behaviour ...

  8. Antinociceptive activity of Eupatorium buniifolium aqueous extract

    African Journals Online (AJOL)

    ebrahimzadeh

    from aerial parts of Salvia limbata produced a statistically significant inhibition of pain induced by hot ... including analgesic and anti-inflammatory activities .... specific antagonist of opioid receptors. The inhibitory effect of naloxone on the antinociceptive activity of extract suggests a morphine-like activity profile for S. limbata.

  9. Antinociceptive potential of Parkia platycephala Benth. in ...

    African Journals Online (AJOL)

    AcOEt 50 mg/kg presented antinociceptive effect in the late phase of formalin test. These findings indicate that E.EtOH and F.AcOEt showed analgesic actions in diabetic rats. Key words: Parkia platycephala, diabetic neuropathy, tactile allodynia, ...

  10. (--Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice

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    Satoh Masamichi

    2011-04-01

    Full Text Available Abstract Background (--Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP receptor in thermal, mechanical, and chemical antinociception induced by (--pentazocine using MOP receptor knockout (MOP-KO mice. Results (--Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from the (--pentazocine-induced mechanical and somatic chemical antinociception experiments, which used the hind-paw pressure and formalin tests, were similar to the results obtained from the thermal antinociception experiments in these mice. However, (--pentazocine retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice, an effect that was completely blocked by pretreatment with nor-binaltorphimine, a KOP receptor antagonist. In vitro binding and cyclic adenosine monophosphate assays showed that (--pentazocine possessed higher affinity for KOP and MOP receptors than for δ-opioid receptors. Conclusions The present study demonstrated the abolition of the thermal, mechanical, and somatic chemical antinociceptive effects of (--pentazocine and retention of the visceral chemical antinociceptive effects of (--pentazocine in MOP-KO mice. These results suggest that the MOP receptor plays a pivotal role in thermal, mechanical, and somatic chemical antinociception induced by (--pentazocine, whereas the KOP receptor is involved in visceral chemical antinociception induced by (--pentazocine.

  11. Antinociceptive and antiulcer activities of Pycnanthus angolensis

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    Margaret Oluwatoyin Sofidiya

    Full Text Available AbstractPycnanthus angolensis (Welw Warb., Myristicaceae, is used in Nigeria folk medicine to treat complaints such as toothache, headache, sore throat, ulcers and wounds. The aim of the study was to investigate the antinociceptive and antiulcer activities of the stem bark extract of Pycnanthus angolensis. Acute toxicity was conducted with a single oral dose of 5 g/kg. Antinociceptive activity was evaluated in acetic acid-induced writhing, formalin and tail immersion tests in mice while antiulcer activity was evaluated in ethanol and indomethacin-induced models in rats. In acetic acid-induced writhing test, the extract (50, 100 and 150 mg/kg, p.o., significantly reduced the number of writhes (46.75%, 57.28% and 75.69% respectively, compared to control. The extract significantly (p < 0.001 reduced the time spent in licking the hind paw at both phases, in formalin test. In tail immersion test, significant antinociceptive effect was only observed with the dose of 150 mg/kg, with peak effect at 90 min (43.38%. There is no significant change in the spontaneous locomotor activity of animals in the open field. The extract prevented the gastric ulceration caused by ethanol and indomethacin treatments compared to control. The results showed that P. angolensis extract possesses antinociceptive and antiulcer activities supporting the traditional use for relieving pain and ulcers.

  12. Convolutamydine A and synthetic analogues have antinociceptive properties in mice.

    Science.gov (United States)

    Figueiredo, Gabriela S M; Zardo, Renata S; Silva, Bárbara V; Violante, Flávio A; Pinto, Angelo C; Fernandes, Patricia D

    2013-01-01

    Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Spinal NGF Restores Opioid Sensitivity in Neuropathic Rats: Possible Role of NGF as a Regulator of CCK-Induced Anti-Opioid Effects

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill

    2000-01-01

    Full Text Available The breadth of peripheral effects produced by nerve growth factor (NGF in nociceptive processing has been well documented. However, less is known about the functional significance of central NGF in nociceptive transmission. The effect of NGF on the nervous system is dependent on the developmental stage. During the prenatal developmental period, NGF is critical for survival of nociceptors; in the postnatal period it regulates the expression of nociceptor phenotype, and in the adult it contributes to pain following an inflammatory insult. The implications for central NGF in the expression and regulation of spinal neuropeptides that are involved in pain mechanisms are reviewed. Knowledge has been gained by studies using peripheral nerve injury models that cause a deprivation of central NGF. These models also give rise to the development of pain syndromes, which encompass spontaneous pain, hyperalgesia and allodynia, routinely referred to as neuropathic pain. These models provide an approach for examining the contribution of central NGF to nociceptive transmission. Chronic pain emanating from a nerve injury is typically refractory to traditional analgesics such as opioids. Recent evidence suggests that supplementation of spinal NGF restores morphine-induced antinociception in an animal model of neuropathic pain. This effect appears to be mediated by alterations in spinal levels of cholecystokinin. The authors hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury.

  14. Antinociceptive activity and mechanism of action of hydroalcoholic extract and dichloromethane fraction of Amphilophium crucigerum seeds in mice.

    Science.gov (United States)

    De Prá, Samira Dal Toé; Ferro, Paula Ronsani; Milioli, Alessandra Marcon; Rigo, Flávia Karine; Chipindo, Orlando Justo; Camponogara, Camila; Casoti, Rosana; Manfron, Melânia Palermo; de Oliveira, Sara Marchesan; Ferreira, Juliano; Trevisan, Gabriela

    2017-01-04

    The medicinal plant generally known as monkey's comb (Amphilophium crucigerum) has been popularly described for the treatment of neuropathic and inflammatory pain, specially seeds preparations. The goal of the present study was to evaluate the antinociceptive effect of the crude extract (Crd) and dichloromethane fraction (Dcm) of A. crucigerum seeds, and investigate the involvement of transient receptor potential vanilloid 1 (TRPV1) receptor in this effect. Male Swiss mice were used in this study. The effects of Crd and Dcm was tested on capsaicin-induced Ca(2+) influx or the specific binding of [(3)H]-resiniferatoxin. Moreover, after treatment with Crd or Dcm, animals were exposed to acute pain (hot water tail-flick and capsaicin intraplantar test) or chronic pain models (injection of complete Freund's adjuvant or partial ligation of the sciatic nerve). Acute adverse effects were also noted: locomotor activity, corporal temperature, hepatic or renal damage, gastrointestinal transit alteration, and ulcerogenic activity. The oral administration of Crd or Dcm resulted in an antinociceptive effect in the hot water tail-flick (48°C) and capsaicin intraplantar tests. Furthermore, these preparations exhibited antinociceptive and anti-inflammatory effects in a chronic inflammatory pain model, and antinociceptive effects in a neuropathic pain model. Moreover, Crd and Dcm reduced capsaicin-induced Ca(2+) influx and diminished the [(3)H]-resiniferatoxin specific binding to spinal cord membranes. Acute adverse events were not found with Crd or Dcm administration. In conclusion, our results support the analgesic effect of A. crucigerum and suggest the presence of compounds that may act as TRPV1 antagonists. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. The Antinociceptive Effect of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K(+) Channels.

    Science.gov (United States)

    Barreras-Espinoza, Israel; Soto-Zambrano, José Alberto; Serafín-Higuera, Nicolás; Zapata-Morales, Ramón; Alonso-Castro, Ángel; Bologna-Molina, Ronell; Granados-Soto, Vinicio; Isiordia-Espinoza, Mario A

    2017-02-01

    Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol-ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP-sensitive K(+) channels in the orofacial formalin-induced nociception model in mice. Drug Dev Res 78 : 63-70, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. The effect of application site of spinal manipulative therapy (SMT) on spinal stiffness.

    Science.gov (United States)

    Edgecombe, Tiffany L; Kawchuk, Greg N; Long, Cynthia R; Pickar, Joel G

    2015-06-01

    Like other factors that can influence treatment efficacy (eg, dosage, frequency, time of day), the site of treatment application is known to affect various physical interventions such as topical anesthetics and cardiopulmonary resuscitation. Like these examples, spinal manipulative therapy (SMT) is a physical intervention that may exhibit maximal benefit when directed to a specific site. Whereas numerous studies of SMT efficacy have produced mixed results, few studies have taken into account the site of SMT application. To determine if the site of SMT application modulates the effect of SMT in an anesthetized feline model. Spinal manipulative therapy applied to specific anatomic locations randomized in a Latin square design with a no-SMT control. Physiologic measures (spinal stiffness). Simulated SMT was delivered by a validated mechanical apparatus to the intact lumbar spine of eight anesthetized felines at four unique sites: L6 spinous process, left L6 lamina, left L6 mammillary process, and L7 spinous process. To measure spinal stiffness, a separate indentation load was applied mechanically to the L6 spinous process before and after each SMT application. Spinal stiffness was calculated from the resulting force-displacement curve as the average stiffness (k) and terminal instantaneous stiffness (TIS). Relative to the no-SMT control, significant decreases in spinal stiffness followed the SMT when L6 spinous and L6 lamina were used as the contact site. Terminal instantaneous stiffness significantly decreased -0.48 N/mm (upper, lower 95% confidence interval [-0.86, -0.09]) with L6 spinous as the contact site and decreased -0.44 N/mm (-0.82, -0.05), with the L6 lamina as the contact site. k increased 0.44 N/mm (-0.01, 088), using L6 spinous as the contact site. Decreases in terminal spinal stiffness were observed after SMT delivered at some application sites but not the others. The results suggest that SMT contact site modulates SMT's effect on spinal stiffness in a

  17. Anti-nociceptive effects of taurine and caffeine in sciatic nerve ...

    African Journals Online (AJOL)

    ABSTRACT. In this study, we investigated the effects of co-administration of taurine and caffeine on thermally induced pain in sciatic nerve ligated rats as well as the roles of autonomic receptors. Rats were rendered neuropathic by unilateral sciatic nerve ligation. The anti-hyperalgesic effect of combined systemic (i.p.) ...

  18. Anti-nociceptive effects of taurine and caffeine in sciatic nerve ...

    African Journals Online (AJOL)

    In this study, we investigated the effects of co-administration of taurine and caffeine on thermally induced pain in sciatic nerve ligated rats as well as the roles of autonomic receptors. Rats were rendered neuropathic by unilateral sciatic nerve ligation. The anti-hyperalgesic effect of combined systemic (i.p.) administration of ...

  19. Evaluation of antinociceptive, anti-inflammatory and anxiolytic activities of methanolic extract of Terminalia citrina leaves

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    Narhari Das

    2015-06-01

    Full Text Available Objective: To investigate the antinociceptive, anti-inflammatory and anxiolytic effects of methanolic extracts of Terminalia citrina (T. citrina leaves (Family: Combretaceae. Methods: The antinociceptive activity was evaluated by acetic acid induced writhing method and radiant heat tail flick method while anti-inflammatory activity was evaluated by human red blood cell membrane stabilization method and anxiolytic activity by elevated plus maze model. Results: The methanolic extract of T. citrina leaves showed significant antinociceptive, antiinflammatory and anxiolytic effects in dose dependent manner compared to their respective standard drugs. Conclusions: The present study demonstrated that T. citrina possesses antinociceptive, antiinflammatory and anxiolytic effects.

  20. Antinociceptive effect of the ethanol extract of the stem bark of ...

    African Journals Online (AJOL)

    The 5th group was given a reference drug either pentazocine (10 mg/kg) or aspirin (100 mg/kg). The extract at 50,100 and ... be dependent on dose. Inhibition of the synthesis of prostaglandins may account for its peripheral analgesic effect, while its action on central receptors may account for its central analgesic activities.

  1. Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

    Directory of Open Access Journals (Sweden)

    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

  2. Evaluation of antinociceptive effect of Petiveria alliacea (guiné) in animals

    OpenAIRE

    Thereza C. M. de Lima; Gina S. Morato; Reinaldo N. Takahashi

    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 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), partic...

  3. Calea zacatechichi dichloromethane extract exhibits antidiarrheal and antinociceptive effects in mouse models mimicking irritable bowel syndrome

    OpenAIRE

    Sałaga, M.; Kowalczuk, A.; Zielinska, M.; Błażewicz, A.; Fichna, J.

    2015-01-01

    Calea zacatechichi Schltdl. (Asteraceae alt. Compositae) is a Mexican plant commonly used in folk medicine to treat respiratory and gastrointestinal (GI) disorders. The objective of this study is to characterize the effect of C. zacatechichi extracts in mouse models mimicking the symptoms of irritable bowel syndrome (IBS). Powdered C. zacatechichi herb (leaves, stems, and flowers) was extracted with methanol. Methanolic extract was filtered and evaporated giving methanolic fraction. The resid...

  4. The immediate effects of spinal thoracic manipulation on respiratory functions

    National Research Council Canada - National Science Library

    Shin, Doo Chul; Lee, Yong Woo

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effects of thoracic spinal manipulation therapy on respiratory function including forced vital capacity and forced expiratory volume in one second...

  5. The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent.

    Science.gov (United States)

    Chen, Wu-Fu; Huang, Shi-Ying; Liao, Chang-Yi; Sung, Chun-Sung; Chen, Jyh-Yih; Wen, Zhi-Hong

    2015-06-01

    The antimicrobial peptide piscidin (PCD)-1 has been reported to have antibacterial and immunomodulatory functions. Here, we investigated the anti-neuropathic properties of PCD-1, in order to determine its potential as a compound to alleviate pain. Treatment with PCD-1 suppressed the inflammatory proteins COX-2 and iNOS in murine macrophage (RAW264.7) and microglial (BV2) cell lines stimulated by lipopolysaccharide (LPS). For studies of the effect of PCD-1 in vivo, mononeuropathy in rats was induced by chronic constriction injury (CCI), and the resulting anti-nociceptive behaviors were compared between CCI controls and CCI rats given intrathecal injections of PCD-1. Much like gabapentin, PCD-1 exerts anti-nociceptive effects against thermal hyperalgesia, with a median effective dose (ED50) of 9.5 μg in CCI rats. In CCI rats, PCD-1 exerted effects against mechanical and cold allodynia, thermal hyperalgesia, and weight-bearing deficits. Furthermore, CCI-mediated activation of microglia and astrocytes in the dorsal horn of the lumbar spinal cord were decreased by PCD-1. In addition, PCD-1 suppressed up-regulation of interleukin-1β (IL-1β) and phosphorylated mammalian target of rapamycin (phospho-mTOR) in CCI rats. Finally, CCI-induced down-regulation of transforming growth factor-β1 (TGF-β1) in rats was attenuated by injection of PCD-1. Taken together, the present findings demonstrate that the marine antimicrobial peptide PCD-1 has anti-nociceptive effects, and thus may have potential for development as an alternative pain-alleviating agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Effects of intrathecal amylin on formalin-induced nociception and on cAMP accumulation in the rat embryonic spinal cells.

    Science.gov (United States)

    Khoshdel, Zahra; Takhshid, Mohammad Ali; Owji, Ali Akbar

    2016-06-01

    Amylin (AMY) is a member of calcitonin family of peptides. In this study, the effects of intrathecal (i.t) injection of AMY on the inflammatory pain and on the cAMP accumulation in the rat spinal cells were investigated. By using AMY receptor antagonists, we also studied the pharmacology of AMY receptors in the spinal cells. Formalin model of inflammatory pain was induced by intraplantar injection of formalin. AMY (0.06250-2500pmol/rat) was administrated i.t 15min before the injection of formalin. Antagonists were injected i.t 10min before the injection of AMY and/or morphine. AMY reduced formalin-induced pain in a dose dependent mode. This effect was inhibited by the potent AMY antagonist, AC187 but not CGRP8-37. rAMY8-37, most commonly reported as a weak AMY antagonist, showed to be equally or more potent than AC187 in antagonizing the above effects. The opioid antagonist, naloxone, had no significant effects on AMY antinociceptive effects. Primary dissociated cell culture was used to investigate the effect of AMY on cAMP production and to characterize AMY receptors in the spinal cells. AMY moderately increases cAMP accumulation in the spinal cells with an EC50 value of 74.62nM. This effect was not affected by CGRP8-37 but was inhibited by AC187 and rAMY8-37 with pA2 values of 7.94 and 7.87 respectively. In conclusion, effects of AMY in reducing formalin induced pain and on the cAMP accumulation by spinal cells are mediated through undefined receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Antinociceptive effect of black seed feeding in streptozotocin-diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohammad reza Vaez mahdavi

    2009-01-01

    Full Text Available   Abstract  Introduction: Diabetic rats display exaggerated hyperalgesic behavior in response to noxious stimuli that may resemble and model aspects of painful diabetic neuropathy in humans. This study was designed to investigate the effect of Nigella sativum (NS on formalin-induced nociceptive responses (standard formalin test in streptozotocin (STZ-induced diabetic rats.  Methods: For this purpose, STZ-diabetic rats received Nigella sativum mixed with standard rat chow at a weight ratio of 6.25% orally for a period of one month.  Results: It was found out that NS treatment did cause a significant reduction in blood glucose in diabetic rats and NS-treated diabetic rats exhibited a lower nociceptive score as compared to untreated-diabetic ones. Meanwhile, NS treatment reduced the nociceptive score in both phases of the formalin test. In contrast, sodium salicylate as positive control only reduced this score in the second phase of the test.  Discussion: The results suggest therapeutic potential of NS feeding for treating painful diabetic neuropathy. 

  8. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    Science.gov (United States)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M.

    2007-01-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses). PMID:16919695

  9. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion.

    Science.gov (United States)

    Knobloch, M; Portier, C J; Levionnois, O L; Theurillat, R; Thormann, W; Spadavecchia, C; Mevissen, M

    2006-11-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses).

  10. The effect of ketamine on intraspinal acetylcholine release

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Goldkuhl, Renée Röstlinger; Nylund, Anders

    2006-01-01

    The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine...... increased the acetylcholine release in high concentrations (100 microM to 10 mM). The results indicate that spinal nicotinic receptors are important for the ketamine-induced acetylcholine release, and that the effect is partly mediated at the spinal level....

  11. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

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    Sagen J

    2016-06-01

    Full Text Available Jacqueline Sagen, Daniel A Castellanos,† Aldric T Hama The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA †Daniel A Castellanos passed away on April 14, 2010 Background: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.Methods: The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.Results: By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the

  12. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

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    Kou-Zhu Zhu

    2013-01-01

    Full Text Available To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg, the native NNAV (untreated with heat; 90 μg/kg, and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

  13. Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models.

    Science.gov (United States)

    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.

  14. 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

  15. Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain.

    Science.gov (United States)

    Araújo, Ianna Wivianne Fernandes; Chaves, Hellíada Vasconcelos; Pachêco, José Mário; Val, Danielle Rocha; Vieira, Lorena Vasconcelos; Santos, Rodrigo; Freitas, Raul Sousa; Rivanor, Renata Line; Monteiro, Valdécio Silvano; Clemente-Napimoga, Juliana Trindade; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2017-03-01

    This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the β-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue. Copyright © 2017. Published by Elsevier B.V.

  16. Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats

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    Nan-Fu Chen

    2014-06-01

    Full Text Available Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI model of neuropathic pain. First, we found that a single intrathecal (i.t. administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-μg flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-β1 (TGF-β1 at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-β type I receptor, blocked the analgesic effects of flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-β1 may be involved in the anti-neuroinflammatory and analgesic effects of flexibilide.

  17. 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.

  18. Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

    Science.gov (United States)

    Simon, Bradley T; Steagall, Paulo V; Monteiro, Beatriz P; Troncy, Eric; Lizarraga, Ignacio

    2016-03-01

    To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. 6 healthy adult cats. In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

  19. Effect of corrective long spinal fusion to the ilium on physical function in patients with adult spinal deformity.

    Science.gov (United States)

    Kondo, Ryo; Yamato, Yu; Nagafusa, Tetsuyuki; Mizushima, Takashi; Hasegawa, Tomohiko; Kobayashi, Sho; Togawa, Daisuke; Oe, Shin; Kurosu, Kenta; Matsuyama, Yukihiro

    2017-08-01

    To identify the effects of corrective long spinal fusion to the ilium on physical function in patients with adult spinal deformity (ASD). Thirty patients who underwent corrective long spinal fusion to the ilium were prospectively analysed. Patients were divided into the ++ group [sagittal vertical axis (SVA) ≥ 95 mm and pelvic tilt (PT) ≥ 30°, 14 patients] and 0+ group (SVA spinal fusion contributed to improving back pain at discharge and gait ability at 12 months in patients with ASD.

  20. Neuroprotective Effect of Ginsenoside Rd in Spinal Cord Injury Rats.

    Science.gov (United States)

    Cong, Lin; Chen, Wenting

    2016-08-01

    In this study, the neuroprotective effects of ginsenoside Rd (GS Rd) were evaluated in a rat model of spinal cord injury (SCI). Rats in SCI groups received a T8 laminectomy and a spinal contusion injury. GS Rd 12.5, 25 and 50 mg/kg were administered intraperitoneally 1 hr before the surgery and once daily for 14 days. Dexamethasone 1 mg/kg was administered as a positive control. Locomotor function was evaluated using the BBB score system. H&E staining and Nissl staining were performed to observe the histological changes in the spinal cord. The levels of MDA and GSH and the activity of SOD were assessed to reflect the oxidative stress state. The production of TNF-α, IL-1β and IL-1 was assessed using ELISA kits to examine the inflammatory responses in the spinal cord. TUNEL staining was used to detect the cell apoptosis in the spinal cord. Western blot analysis was used to examine the expression of apoptosis-associated proteins and MAPK proteins. The results demonstrated that GS Rd 25 and 50 mg/kg significantly improved the locomotor function of rats after SCI, reduced tissue injury and increased neuron survival in the spinal cord. Mechanically, GS Rd decreased MDA level, increased GSH level and SOD activity, reduced the production of pro-inflammatory cytokines and prevented cell apoptosis. The effects were equivalent to those of dexamethasone. In addition, GS Rd effectively inhibited the activation of MAPK signalling pathway induced by SCI, which might be involved in the protective effects of GS Rd against SCI. In conclusion, GS Rd attenuates SCI-induced secondary injury through reversing the redox-state imbalance, inhibiting the inflammatory response and apoptosis in the spinal cord tissue. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

    Science.gov (United States)

    Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

    2016-09-05

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

  2. [Effect of intrathecal ketamine injection on protein kinase C expression in the spinal dorsal horn of rats with formalin-induced pain].

    Science.gov (United States)

    YANG, Yong; GUO, Qu-lian; ZOU, Wang-yuan; WANG, E; YAN, Jian-qin

    2011-03-01

    To investigate the expression of protein kinase C (PKC) in the spinal dorsal horn of rats with formalin-induced pain and the effect of intrathecal ketamine on PKC expression. Thirty-two SD rats were randomly divided into 4 equal groups, namely the control group, intrathecal saline group (NS), 50 µg ketamine group (K1) and 100 µg ketamine group (K2). The rats were anesthetized with 10% chloral hydrate, and a microspinal catheter was inserted intrathecally into the lumbar region. Five days later, the rats in groups, K1 and K2 were subjected to intrathecal administration of 50 and 100 µg ketamine (10 µl), respectively, followed by 10 µl saline, and those in NS group received 20 µl saline only. Thirty minutes later, 5% formalin (50 µl) was subcutaneously injected into the left hindpaw. The pain intensity score (PIS) was utilized to assess antinociceptive behavior within 1 h after formalin injection. Twenty-four hours later, the left hindpaw thickness was measured and the expression of PKC in the spinal dorsal horn in the L5 segment was assayed using immunohistochemistry. Compared to group NS, groups K1 and K2 showed significantly decreased PIS (Phorn were significantly higher in group NS than in group C (Phorn in response to formalin-induced pain, suggesting the important role of PKC in nociceptive signal transmission and modulation in the spinal cord.

  3. Antinociceptive Activity of Zanthoxylum piperitum DC. Essential Oil

    Science.gov (United States)

    Donald, Graciela Rocha; Fernandes, Patrícia Dias

    2016-01-01

    Zanthoxylum piperitum DC. (ZP) is a traditional medicinal plant used mainly in countries from Asia such as Japan. This study aimed to investigate the antinociceptive effect of ZP essential oil (ZPEO). The major component present in the essential oil was beta-phellandrene (29.39%). Its antinociceptive activity was tested through animal models (formalin-, capsaicin-, and glutamate-induced paw licking and hot plate). The anti-inflammatory effect was evaluated through the carrageenan-induced leukocyte migration into the subcutaneous air pouch (SAP), with measurement of cytokines. The results showed antinociceptive effect for ZPEO for the first phase of the formalin-induced licking, glutamate, and hot plate tests. However, ZPEO had no effect on reducing paw licking induced by capsaicin. Finally, ZPEO had no effect against inflammation induced by carrageenan. PMID:27547225

  4. Antinociceptive Activity of Zanthoxylum piperitum DC. Essential Oil

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    Graciela Rocha Donald

    2016-01-01

    Full Text Available Zanthoxylum piperitum DC. (ZP is a traditional medicinal plant used mainly in countries from Asia such as Japan. This study aimed to investigate the antinociceptive effect of ZP essential oil (ZPEO. The major component present in the essential oil was beta-phellandrene (29.39%. Its antinociceptive activity was tested through animal models (formalin-, capsaicin-, and glutamate-induced paw licking and hot plate. The anti-inflammatory effect was evaluated through the carrageenan-induced leukocyte migration into the subcutaneous air pouch (SAP, with measurement of cytokines. The results showed antinociceptive effect for ZPEO for the first phase of the formalin-induced licking, glutamate, and hot plate tests. However, ZPEO had no effect on reducing paw licking induced by capsaicin. Finally, ZPEO had no effect against inflammation induced by carrageenan.

  5. Task performance in spinal cord injury: effect of helplessness training.

    Science.gov (United States)

    Wool, R N; Siegel, D; Fine, P R

    1980-07-01

    The effects of failure or helplessness training on the task performance of recently injured spinal cord patients were assessed using the learned helplessness theory as a model. The theory states that individuals who experience uncontrollable failure become depressed and feel helpless, while those who experience self-controlled success develop a sense of competence and feel industrious. To provide validation of the learned helplessness theory, 24 recently injured spinal cord patients were interviewed and then tested for helplessness effects and depression on 2 standard learned helplessness tasks. Results suggest that it may be possible to immunize spinal cord injured patients against debilitating emotional reactions to paralysis with a success-oriented rehabilitation regime during the initial stages of recovery.

  6. Does the effectiveness of core stability exercises correlate with the severity of spinal stenosis in patients with lumbar spinal stenosis?

    Science.gov (United States)

    Chen, Chaxiang; Lin, Zhichao; Zhang, Yingjie; Chen, Zemin; Tang, Shujie

    2017-01-01

    To determine whether the effectiveness of core stability exercises correlates with the severity of spinal stenosis in patients with degenerative lumbar spinal stenosis. Forty-two patients with degenerative lumbar spinal stenosis treated in the department of orthopedics of our hospital between May 2013 and January 2016 were included in the study. All the patients performed core stability exercises once daily for six weeks, and the clinical outcomes were evaluated using Japanese Orthopaedic Association (JOA) score and self-reported walking capacity. The anteroposterior osseous spinal canal diameter was measured to evaluate the severity of spinal stenosis. The correlation between the stenosis degree and the differences of Japanese Orthopaedic Association score or self-reported walking capacity at baseline and after treatment were analyzed. The patients were divided into three groups according to the spinal stenosis degree. In the three groups, there was no significant difference in JOA or self-reported walking distance at baseline (p>0.05) and after treatment (p>0.05). The JOA scores and self-reported walking distance were significantly increased after treatment (p0.05) or self-reported walking distance (p>0.05). There was no significantcorrelation between the effectiveness of core stability exercises and the severity of spinal stenosis in patients with degenerative lumbar spinal stenosis.

  7. Effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions

    DEFF Research Database (Denmark)

    Laessøe, Line; Sønksen, Jens; Bagi, Per

    2003-01-01

    We examined the effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions.......We examined the effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions....

  8. Antispastic effect of penile vibration in men with spinal cord lesion

    DEFF Research Database (Denmark)

    Læssøe, Line; Nielsen, Jens Bo; Biering-Sørensen, F.

    2004-01-01

    To evaluate the possible antispastic effect of penile vibratory stimulation (PVS) in men with spinal cord lesion (SCL).......To evaluate the possible antispastic effect of penile vibratory stimulation (PVS) in men with spinal cord lesion (SCL)....

  9. Opioidergic orofacial antinociception induced by electroacupuncture at acupoint St36

    Directory of Open Access Journals (Sweden)

    R.T. Almeida

    2008-07-01

    Full Text Available The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 ± 0.1; 30 Hz: 1.8 ± 0.1; 100 Hz: 1.7 ± 0.1 vs 1.4 ± 0.2. The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 ± 0.2 vs 1.0 ± 0.1 was used, and not with 5 or 30 Hz (1.2 ± 0.2 and 0.7 ± 0.1 vs 1.0 ± 0.1. The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously antagonized it (1.8 ± 0.2 and 1.7 ± 0.2 vs 3.0 ± 0.1.

  10. Effectiveness and Safety of Tranexamic Acid in Spinal Deformity Surgery.

    Science.gov (United States)

    Choi, Ho Yong; Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2017-01-01

    Spinal deformity surgery has the potential risk of massive blood loss. To reduce surgical bleeding, the use of tranexamic acid (TXA) became popular in spinal surgery, recently. The purpose of this study was to determine the effectiveness of intra-operative TXA use to reduce surgical bleeding and transfusion requirements in spinal deformity surgery. A total of 132 consecutive patients undergoing multi-level posterior spinal segmental instrumented fusion (≥5 levels) were analyzed retrospectively. Primary outcome measures included intraoperative estimated blood loss (EBL), transfusion amount and rate of transfusion. Secondary outcome measures included postoperative transfusion amount, rate of transfusion, and complications associated with TXA or allogeneic blood transfusions. The number of patients was 89 in TXA group and 43 in non-TXA group. There were no significant differences in demographic or surgical traits between the groups except hypertension. The EBL was significantly lower in TXA group than non-TXA group (841 vs. 1336 mL, p=0.002). TXA group also showed less intra-operative and postoperative transfusion requirements (544 vs. 812 mL, p=0.012; 193 vs. 359 mL, p=0.034). Based on multiple regression analysis, TXA use could reduce surgical bleeding by 371 mL (37 % of mean EBL). Complication rate was not different between the groups. TXA use can effectively reduce the amount of intra-operative bleeding and transfusion requirements in spinal deformity surgery. Future randomized controlled study could confirm the routine use of TXA in major spinal surgery.

  11. ASSESSMENT OF ANTI-NOCICEPTIVE EFFICACY OF COSTUS SPECIOSUS RHIZOME IN SWISS ALBINO MICE

    Directory of Open Access Journals (Sweden)

    Upendra Nagaich

    2010-03-01

    Full Text Available Present study attempts to evaluate the anti-nociceptive activity of the aqueous andethanol extracts of Costus speciosus rhizome (CPA and CPE in Swiss albino mice. Themaceration extracts were evaluated for anti-nociceptive activity by acetic acid-inducedwrithing and tail flick method in mice. The anti-nociceptive screening revealedsignificant peripheral anti-nociceptive actions of both extracts against acetic acid inducedwrithing in mice. Aqueous extract (CPA significantly inhibited writhes at the dose of 75and 150 mg/kg body weight, while ethanol extract (CPE produced significant protectionat the dose of 150 mg/kg body weight. However, in tail flick method only the ethanolextract (CPE showed significant central analgesic action, while aqueous extract wastotally ineffective. The present investigation demonstrates that the rhizome extracts of C.speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.

  12. Effect of ship motion on spinal loading during manual lifting

    NARCIS (Netherlands)

    Faber, G.S.; Kingma, I.; Delleman, N.; Dieën, J. van

    2008-01-01

    This study investigated the effects of ship motion on peak spinal loading during lifting. All measurements were done on a ship at sea. In 1-min trials, which were repeated over a wide range of sailing conditions, subjects lifted an 18 kg box five times. Ship motion, whole body kinematics, ground

  13. Low-dose spinal anaesthesia provides effective labour analgesia ...

    African Journals Online (AJOL)

    Low-dose spinal anaesthesia provides effective labour analgesia and does not limit ambulation. T Anabaha*, A Olufolabia,b,d, J Boydc and R Georgec,d. aSchool of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana. bDuke University Medical Centre, Durham, NC, USA. cIWK Health Centre ...

  14. Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

    Science.gov (United States)

    2013-01-01

    Background This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively. Results Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively

  15. [Effect of the music-therapy under spinal anesthesia].

    Science.gov (United States)

    Maeyama, Akihiko; Kodaka, Mitsuharu; Miyao, Hideki

    2009-06-01

    Since no pre-medication has been widely accepted especially in spinal anesthesia, anesthesiologists should manage the control of patient's anxiety during surgery. Instead of sedatives, we have been using music-therapy during spinal anesthesia. Bispectral index monitoring (BIS) is used as one of the sedation indices in spinal anesthesia. The aim of this study was to assess the music-therapy on reducing anxiety of patients under spinal anesthesia using BIS and interview type psychology test, State Trait Anxiety Inventory (STAI). Fifty-eight ASA physical status I-II patients scheduled for spinal anesthesia, were randomly allocated into M group (music group, n=29) or C group (control, n=29). BIS, EMG, and SQI of both groups were obtained continuously with computer system. Patients in M group listened to music by head phone and those in C group were left free under ordinary operating theater environment. Trait Anxiety Inventory (STAI-TA) score was obtained preoperatively for property-based anxiety and the State Anxiety Inventory (STAI-SA) score was obtained postoperatively for condition-based anxiety. Time averaged BIS scores (pre-surgery, during-surgery and post-surgery period)were obtained during operation. Time averaged BIS values of M and C group in pre-surgery period, during-surgery period, and post-surgery period were 95.3+/-0.4 vs 95.8+/-0.4 (NS), 87.6+/-7.5 vs 95.1+/-2.8 (Pscores of both groups were not different. Music-therapy reduced BIS value and was effective to reduce patient's anxiety during spinal anesthesia.

  16. Antinociceptive effect of Aristolochia trilobata stem essential oil and 6-methyl-5-hepten-2yl acetate, its main compound, in rodents.

    Science.gov (United States)

    Quintans, Jullyana de Souza Siqueira; Alves, Rafael Dos Santos; Santos, Darlisson de Alexandria; Serafini, Mairim Russo; Alves, Péricles Barreto; Costa, Emmanoel Vilaça; Zengin, Gokhan; Quintans-Júnior, Lucindo José; Guimarães, Adriana Gibara

    2017-03-01

    Aristolochia trilobata L. is an aromatic plant, popularly known as "mil-homens", and its essential oil (EO) is generally used to treat colic, diarrhea and dysentery disorders. We evaluated the antinociceptive effect of A. trilobata stem EO and of its major compound, the (R)-(-)-6-methyl-5-hepten-2-yl acetate (sulcatyl acetate: SA), using acetic acid (0.85%)-induced writhing response and formalin-induced (20 μL of 1%) nociceptive behavior in mice. We also evaluated the EO and SA effect on motor coordination, using the rota-rod apparatus. EO (25, 50 and 100 mg/kg) or SA (25 and 50 mg/kg) reduced nociceptive behavior in the writhing test (p<0.001). EO (100 mg/kg) and SA (25 and 50 mg/kg) decreased the nociception on the first phase of the formalin test (p<0.05). On the second phase, EO (25: p<0.01; 50: p<0.05 and 100 mg/kg: p<0.001) and SA (25 and 50 mg/kg; p<0.001) reduced the nociceptive response induced by formalin. EO and SA were not able to cause changes in the motor coordination of animals. Together, our results suggest that EO has an analgesic profile and SA seems to be one of the active compounds in this effect.

  17. Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model

    Directory of Open Access Journals (Sweden)

    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.

  18. Spinal vasopressin alleviates formalin-induced nociception by enhancing GABAA receptor function in mice.

    Science.gov (United States)

    Peng, Fang; Qu, Zu-Wei; Qiu, Chun-Yu; Liao, Min; Hu, Wang-Ping

    2015-04-23

    Arginine vasopressin (AVP) plays a regulatory role in nociception. Intrathecal administration of AVP displays an antinociceptive effect. However, little is understood about the mechanism underlying spinal AVP analgesia. Here, we have found that spinal AVP dose dependently reduced the second, but not first, phase of formalin-induced spontaneous nociception in mice. The AVP analgesia was completely blocked by intrathecal injected SR 49059, a vasopressin-1A (V1A) receptor antagonist. However, spinal AVP failed to exert its antinociceptive effect on the second phase formalin-induced spontaneous nociception in V1A receptor knock-out (V1A-/-) mice. The AVP analgesia was also reversed by bicuculline, a GABAA receptor antagonist. Moreover, AVP potentiated GABA-activated currents in dorsal root ganglion neurons from wild-type littermates, but not from V1A-/- mice. Our results may reveal a novel spinal mechanism of AVP analgesia by enhancing the GABAA receptor function in the spinal cord through V1A receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal Cord Ischemia/Reperfusion Injury in Rabbits.

    Science.gov (United States)

    Li, Huixian; Dong, Xiuhua; Jin, Mu; Cheng, Weiping

    2018-01-18

    Delayed paraplegia due to spinal cord ischemia/reperfusion injury (IRI) remains one of the most severe complications of thoracoabdominal aneurysm surgery, for which effective prevention and treatment is still lacking. The current study investigates whether spinal cord stimulation (SCS) postconditioning has neuroprotective effects against spinal cord IRI. Ninety-six New Zealand white male rabbits were randomly divided into four groups as follows: a sham group and three experimental groups (C group, 2 Hz group, and 50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C underwent no additional intervention, while rabbits in the other two experimental groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of reperfusion and then daily until sacrifice. Hind limb neurologic function of rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested immediately after sacrifice for histological examination and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The number of viable α-motor neurons in ventral horn was counted and TUNEL-positive rate of α-motor neurons was calculated. Spinal cord IRI was caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group demonstrated better hind limb motor function and a lower rate of TUNEL-positive α-motor neuron after eight hours, one day, three days, and seven days of spinal cord reperfusion. More viable α-motor neurons were preserved after one and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group and 50 Hz group rabbits. SCS postconditioning at 2 Hz protected the spinal cord from IRI. © 2018 International Neuromodulation Society.

  20. Effectiveness of intraoperative neurophysiological monitoring during spinal surgery

    Directory of Open Access Journals (Sweden)

    Valentina А. Kuzmina

    2016-12-01

    Conclusions. The application of IONM minimized the need for the wake-up test and significantly decreased the incidence of neurological complications caused by injury to the spinal cord and spinal roots during execution of spinal manipulations.

  1. Effect of Fibromyalgia Symptoms on Outcome of Spinal Surgery.

    Science.gov (United States)

    Ablin, Jacob N; Berman, Mark; Aloush, Valerie; Regev, Gilad; Salame, Khalil; Buskila, Dan; Lidar, Zvi

    2017-04-01

    To evaluate the effect of presurgical symptoms characteristic of fibromyalgia on the postsurgical outcome of patients undergoing spinal surgery. In this observational cohort study, participants were patients scheduled for spinal surgery, including cervical or lumbar laminectomy and foraminectomy. Presurgical evaluation included physical examination and manual dolorimetry. Questionnaires included the widespread pain index (WPI), symptom severity scale (SSS), and SF-36. Postsurgical evaluation performed at 10-12 weeks included questionnaires, physical examination, and dolorimetry. Forty patients (21 male, 19 female) were recruited. Four patients (10%) fulfilled American College of Rheumatology (ACR) 1990 fibromyalgia; nine patients fulfilled 2010 criteria (22.5%). Overall, a significant 34% reduction in WPI was observed postsurgically ( P  component postsurgically. A significant negative correlation was observed between presurgical SSS and change in composite physical functioning SF-36 component. Regression analysis demonstrated a difference in trend between FMS-positive and FMS-negative patients regarding postop changes in SSS, as well as a difference in trend regarding the general health role limitation due to emotional problems and pain components of the SF-36. Fibromyalgia symptoms were highly prevalent among patients scheduled for spinal surgery. A negative correlation was observed between presurgical severity of fibromyalgia symptoms and components of postsurgical SF-36. Patients with symptoms typical of fibromyalgia may have a less favorable outcome after spinal surgery. The clinical utility of surgical intervention in such patients should be carefully evaluated, and treatment specific for fibromyalgia might be considered before embarking on a surgical course.

  2. Sexual differentiation of rat reproductive versus opioid antinociceptive systems.

    Science.gov (United States)

    Craft, Rebecca M; Ulibarri, Catherine

    2009-01-01

    It has been suggested that sexual differentiation of opioid analgesic sensitivity may parallel sexual differentiation in reproductive systems. The present study compared organizational and activational roles of testosterone in sexual differentiation in reproductive versus opioid antinociceptive systems in the rat, to assess whether both systems were similarly testosterone dependent. Male rat pups (Sprague-Dawley and Fisher 344 [F344]) were either handled or castrated on postnatal day (PND) 1, and female pups were injected with testosterone propionate (100 or 1000 microg) on PND 2. In adulthood, all rats were gonadectomized (or simply anesthetized) and implanted with either testosterone filled or blank capsules (one 10-mm capsule/100 g of body weight). Two hundred one Sprague-Dawley rats and 178 F344 rats were used. In gonadally intact adults of both rat strains, the antinociceptive potency of subcutaneously injected morphine was significantly greater in males than in females (P defeminization of sexual behavior, ovary weight, and body weight generally met conventional expectations. Compared with male controls, neonatally castrated males gained less body weight, and displayed more lordosis behavior and compromised male sexual behaviors. Compared with female controls, neonatally androgenized females gained more body weight, developed smaller ovaries, and presented less lordosis behavior and more male sexual behaviors. Overall, neonatal testosterone manipulations sufficient to masculinize or defeminize rats in terms of reproductive behavior and physiology also masculinized or defeminized morphine antinociceptive sensitivity. The effects of neonatal castration were reversed by adult testosterone treatment, indicating that sexual differentiation of opioid antinociceptive systems begins before PND 1. Sensitivity to opioid antinociception begins to diverge between males and females early in life. The relationship between gonadal hormone-mediated sexual differentiation of

  3. Effects of Type of Work and Age on Spinal Shrinkage | Ismaila ...

    African Journals Online (AJOL)

    spine. The present study was aimed at studying the effects of different types of work on spinal shrinkage. Moreover, the relationship between age and spinal shrinkage was also studied. The heights just before the start and after the close of work were measured in order to determine the spinal shrinkage. The study confirmed ...

  4. Effects of magnesium sulfate on spinal cord tissue lactate and malondialdehyde levels after spinal cord trauma.

    Science.gov (United States)

    Ozdemir, M; Cengiz, Sahika Liva; Gürbilek, M; Oğün, T C; Ustün, M E

    2005-09-01

    In the present study, the effects of magnesium sulfate (MgSO4) on tissue lactate and malondialdehyde (MDA) levels after spinal cord trauma (SCT) in rabbits were studied. Thirty New Zeland rabbits. Interventions. The rabbits were divided equally into three groups: group I was the sham- operated group, group II suffered from SCT but received no treatment, group III was given a dose of 100 mg/kg of magnesium sulfate intravenously at 5th minute after SCT. MEASUREMENTS. The lactate and MDA levels were measured in contused spinal cord tissue at 60 minutes after SCT. There was a significant increase of lactate and MDA levels in group II (p < 0.05) when compared with groups I and III, and a significant increase in the level of MDA in group III compared with group I, and also a significant decrease compared with group II, which was the trauma group without treatment (p < 0.05). The findings of this study showed that magnesium sulfate can attenuate the increase of tissue MDA and supply a normalization of lactate levels following SCT which may be related to the neuroprotective effects of (MgSO4).

  5. Effect of nimodipine on rat spinal cord injury.

    Science.gov (United States)

    Jia, Y-F; Gao, H-L; Ma, L-J; Li, J

    2015-02-13

    We evaluated the potentially protective effect of nimodipine on rat spinal cord injury. Sprague-Dawley rats received spinal cord injury, and were separated into nimodipine (N = 12) and saline groups (N = 12). Within 1 h of the injury, rats were treated intraperitoneally with nimodipine (1.0 mg/kg) or an equal amount of saline. Treatment was performed 3 times a day for 1 week. Operation BBB score and track experiment were used to measure the physical function of the hind legs 1 and 2 weeks after injury. Two weeks after the injury, malondialdehyde (MDA) content and spinal cord myeloperoxidase (MPO) activity of the injured part were determined, and the glial scar and dead room were studied using the immune tissue chemical test. ED1 was used to observe active gitter cell and macrophages. The physical function of the nimodipine group improved significantly (P nimodipine group (nmol/g, 25.6 ± 9.7 vs 68.5 ± 16.7) and MPO activity (U/g, 252.2 ± 63.9 vs 382.8 ± 108.2) decreased significantly (P nimodipine whole dead space (mm2, 4.45 ± 1.28 vs 6.16 ± 2.65) and ED1 antibody immunity colored positive room (mm2, 1.87 ± 0.42 vs 2.86 ± 1.01) reduced significantly (P Nimodipine treatment could reduce oxidative injury after spinal cord injury, reduce the whole dead space and inflammation, and repair spinal cord injury.

  6. Hyptis pectinata: redox protection and orofacial antinociception.

    Science.gov (United States)

    Paixão, M S; Melo, M S; Oliveira, M G B; Santana, M T; Lima, A C B; Damascena, N P; Dias, A S; Araujo, B S; Estevam, C S; Botelho, M A; Quintans, L J

    2013-09-01

    Hyptis pectinata L. Poit, known as 'sambacaitá', is used in Brazil to treat inflammatory and painful disorders. In this study, the antioxidant and orofacial antinociceptive properties of the aqueous extract of H. pectinata leaves (AEPH) were assessed using in vitro and in vivo models. Thus, AEPH reduced the 2,2-diphenyl-1-picrylhydrazyl radical up to 72.10% with an EC₅₀ of 14.56 µg/ml. It also inhibited 40.80% of the lipoperoxidation induced by 2'-azobis (2-amidinopropane) dihydrochloride in the thiobarbituric acid-reactive substances assay. The orofacial antinociceptive activity was evaluated in mice pre-treated with AEPH (100, 200 and 400 mg/kg, p.o.) and morphine (5 mg/kg, i.p.), which received afterwards formalin- (20 µl, 2% solution, s.c.), glutamate- (40 µl, 25 mM, s.c.) and capsaicin- (20 µl, 2.5 µg, s.c.) to induce orofacial nociception. AEPH at all doses reduced (p < 0.001) the nociceptive response in the first (43-62%) and second (47-80%) phases of the formalin test. Besides, the effect of AEPH (400 mg/kg) was not changed in the presence of naloxone (1.5 mg/kg, i.p.), an opioid antagonist. AEPH significantly inhibited mice face rubbing for capsaicin (23-69%, p < 0.05) and glutamate (48-77%, p < 0.001) at all doses. The findings suggested the AEPH has peripheral and central antinociceptive activities, which are not related to opioid receptors. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Effect of Combination of Non-Invasive Spinal Cord Electrical Stimulation and Serotonin Receptor Activation in Patients with Chronic Spinal Cord Lesion.

    Science.gov (United States)

    Moshonkina, T R; Shapkova, E Yu; Sukhotina, I A; Emeljannikov, D V; Gerasimenko, Yu P

    2016-10-01

    We analyzed the efficiency of percutaneous electrical stimulation of the spinal cord and serotonin receptor activation in rehabilitation of paralyzed patients. Four-week course of spinal cord electrical stimulation combined with mechanotherapy produced positive shifts in the status of chronically paralyzed patients. Serotonin receptor activation potentiated the effect of spinal cord stimulation and can be regarded as an additional neurorehabilitation option.

  8. Effect of lidocaine on spinal cord lipid peroxide levels after acute spinal cord trauma in rats

    OpenAIRE

    Yalçın, A.S.; Özer, F.; Pamir, N.; Emerk, K.

    1991-01-01

    A standard spinal cord trauma was performed on control and lidocaine-treated (5 mg/kg. i.p.) rats. Spinal cord lipid peroxide levels in the lidocaine-trcaled group were significantly lower than those of controls. No significant difference was observed in plasma lipid peroxide levels. Our results suggest a protective role of lidocaine against lipid peroxidation after experimental spinal cord trauma in rats.

  9. Antinociceptive activity of the essential oil from Artemisia ludoviciana.

    Science.gov (United States)

    Anaya-Eugenio, Gerardo D; Rivero-Cruz, Isabel; Bye, Robert; Linares, Edelmira; Mata, Rachel

    2016-02-17

    Aerial parts of Artemisia ludoviciana are widely used in Mexico for treating gastrointestinal disorders, painful complaints and diabetes. To establish the preclinical efficacy as antinociceptive agent of the essential oil (EO) from the aerial parts of A. ludoviciana using well-known animal models. Acute antinociceptive effect of EO (1, 10, 31.6, 100, and 316mg/kg, i.p.) was evaluated using the hot plate and paw formalin models in mice. The motor effects were assessed with the rota-rod and open field assays. The volatile components obtained by headspace solid phase microextraction (HS-SPME) and hydrodistillation were determined using gas chromatography coupled with mass spectrometry (GC-MS) analysis. EO decreased first and second phases of formalin test; in the first stage, the better effect was obtained with the treatment of 316mg/kg but in the second phase, time licking was attenuated at the doses of 31.6, 100 and 316mg/kg. The effectiveness of EO (ED50=25.9mg/kg) for attenuating neurogenic pain was corroborated using the hot plate test. The antinociceptive action of EO was blocked by naloxone suggesting that its mode of action involved an opioid mechanism. Furthermore, EO (316mg/kg) did not affect animal motor and coordination functions when tested by the rota-rod and open field tests. The latter results indicated that the pharmacological effects exerted by EO during the hot plate and formalin test are truly antinociceptive. GC-MS analysis of EO revealed that (±)-camphor, γ-terpineol, 1,8-cineole and borneol were the major volatile compounds of the plant. EO from A. ludoviciana showed significant antinociceptive effect, which appeared to be partially mediated by the opioid system. These findings could support the long-term use of A. ludoviciana for treating painful complaints in Mexican folk medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass.

    Science.gov (United States)

    Ong, Hui Ming; Mohamad, Azam Shah; Makhtar, Nor 'Adilah; Khalid, Mohamed Hanief; Khalid, Syamimi; Perimal, Enoch Kumar; Mastuki, Siti Nurulhuda; Zakaria, Zainul Amiruddin; Lajis, Nordin; Israf, Daud Ahmad; Sulaiman, Mohd Roslan

    2011-01-07

    Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache. The study was carried out to investigate the antinociceptive effect of the methanolic extract of A. uliginosa (Sw.) Cass. flowers (MEAU) using murine models of chemicals and thermal nociception. Chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-induced paw licking test) and thermal models (hot plate test) of nociception in mice were employed to evaluate the MEAU analgesic effect. The extract was given via oral administration at doses of 3, 10, 30 and 100 mg/kg. It was demonstrated that MEAU produced significant antinociceptive response in all the chemical- and thermal-induced nociception models, which indicates the presence of both centrally and peripherally mediated activities. Furthermore, the reversal of antinociception of MEAU by naloxone suggests the involvement of opioid system in its centrally mediated analgesic activity. Moreover, MEAU-treated mice did not show any significant motor performance alterations. No mortality and signs of toxicity were recorded following treatment of the MEAU. The results from the present study appear to support the folkloric belief in the medicinal properties of A. uliginosa (Sw.) Cass. which against pain at both central and peripheral levels, in which the central antinociception is probably due to the participation of the opioid receptors. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Antinociception induced by systemic administration of local anaesthetics depends on a central cholinergic mechanism.

    Science.gov (United States)

    Bartolini, A; Galli, A; Ghelardini, C; Giotti, A; Malcangio, M; Malmberg-Aiello, P; Zucchi, P L

    1987-12-01

    1 The antinociceptive effects of systemically-administered procaine, lignocaine and bupivacaine were examined in mice and rats by using the hot-plate, writhing and tail flick tests. 2 In both species all three local anaesthetics produced significant antinociception which was prevented by atropine (5 mg kg-1, i.p.) and by hemicholinium-3 (1 microgram per mouse, i.c.v.), but not by naloxone (3 mg kg-1, i.p.), alpha-methyl-p-tyrosine (100 mg kg-1, s.c.), reserpine (2 mg kg-1, i.p.) or atropine methylbromide (5.5 mg kg-1, i.p.). 3 Atropine (5 mg kg-1, i.p.) which totally antagonized oxotremorine (40 micrograms kg-1, s.c.) antinociception did not modify morphine (5 mg kg-1, s.c.) or baclofen (4 mg kg-1, s.c.) antinociception. On the other hand, hemicholinium, which antagonized local anaesthetic antinociception, did not prevent oxotremorine, morphine or baclofen antinociception. 4 Intracerebroventricular injection in mice of procaine (200 micrograms), lignocaine (150 microgram) and bupivacaine (25 micrograms), doses which were largely ineffective by parenteral routes, induced an antinociception whose intensity equalled that obtainable subcutaneously. Moreover, the i.c.v. injection of antinociceptive doses did not impair performance on the rota-rod test. 5 Concentrations below 10(-10) M of procaine, lignocaine and bupivacaine did not evoke any response on the isolated longitudinal muscle strip of guinea-pig ileum, or modify acetylcholine (ACh)-induced contractions. On the other hand, they always increased electrically-evoked twitches. 6 The same concentrations of local anaesthetics which induced antinociception did not inhibit acetylcholinesterase (AChE) in vitro. 7 On the basis of the above findings and the existing literature, a facilitation of cholinergic transmission by the local anaesthetics is postulated; this could be due to blockade of presynaptic muscarinic receptors.

  12. Costs and effects in lumbar spinal fusion

    DEFF Research Database (Denmark)

    Soegaard, Rikke; Christensen, Finn Bjarke; Christiansen, Terkel

    2007-01-01

    Although cost-effectiveness is becoming the foremost evaluative criterion within health service management of spine surgery, scientific knowledge about cost-patterns and cost-effectiveness is limited. The aims of this study were (1) to establish an activity-based method for costing at the patient......, whereas the probability of anterior intervertebral support being cost-effective escalates as willingness-to-pay per effect unit increases. This study reveals useful and hitherto unknown information both about cost-patterns at the patient-level and determinants of cost-effectiveness. The overall conclusion...

  13. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  14. Identification of antinociceptive fraction of snake venom from Crotalus durissus collilineatus crotamine-negative and its acute toxicity evaluation.

    Science.gov (United States)

    de Oliveira, Sayonara Ay More; Magalhães, Marta Regina; de Oliveira, Lilibete P; da Cunha, Luiz Carlos

    2016-11-01

    The crude venom of the snake Crotalus durissus collilineatus (CDC) promotes neurological signs and symptoms in accidents involving humans and animals and the victims reports analgesia at the bite site, without tissue destruction. Studies shows that CDC has analgesic activity, among others. The crude venom is considered unsuitable for therapeutic purposes, with encouragement to the fractionation and purification of the same. Thus, the aim with CDC venom is: to perform fractionation by preparative HPLC; to test the antinociceptive activity of fractions and acute toxicity of active fractions. The CDC was fractionated on preparative HPLC-PDA (Oliveira et al., 2015) and the fractions were tested for their antinociceptive activity for writhing test by acetic acid (0.6%) in mice. For one of the fractions, which showed high analgesic effect both p.o. and i.p. routes, it evaluated the acute toxicity by the up and down method (OECD, 2001). In the fractionation by HPLC-PDA, CDC yielded 10 peaks (P1P10). SDS-PAGE showed that there was a good separation of components of the venom. All peaks were evaluated for their ability to reduce writhing, and the only one that apparently showed antinociceptive effect was Fr5 fraction (40 μg/kg). The Fr5 was able to reduce by 47% the number of contortions (i.p.) and 87% (p.o.), compared to control. The Fr5 fraction showed no morbidity and no mortality in the acute toxicity test (dose of 1000 μg/kg, p.o.); so it was not possible to estimate the LD50. According to the results, it can be stated that the venom and Fr5 of Crotalus durissus collilineatus snake of crotamine-negative type, may exhibit antinociceptive activity by suppressing nociception induced by acetic acid, suggesting it is related to effects on peripheral sites spinal and presents low acute toxicity values in experimental animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The effect of spinal manipulative therapy on spinal range of motion: a systematic literature review

    Directory of Open Access Journals (Sweden)

    Millan Mario

    2012-08-01

    Full Text Available Abstract Background Spinal manipulative therapy (SMT has been shown to have an effect on spine-related pain, both clinically and in experimentally induced pain. However, it is unclear if it has an immediate noticeable biomechanical effect on spinal motion that can be measured in terms of an increased range of motion (ROM. Objective To assess the quality of the literature and to determine whether or not SMT is associated with an immediate increase in ROM. Design A systematic critical literature review. Method Systematic searches were performed in Pubmed, the Cochrane Library and EMBASE using terms relating to manipulation, movement and the spine. Selection of articles was made according to specific criteria by two independent reviewers. Two checklists were created based on the needs of the present review. Articles were independently reviewed by two reviewers. Articles were given quality scores and the data synthesized for each region treated in the literature. Findings were summarized in tables and reported in a narrative fashion. Results Fifteen articles were retained reporting on experiments on the neck, lumbar spine, hip and jaw. The mean quality score was 71/100 (ranges 33/100 - 92/100. A positive effect of SMT was reported in both studies where mouth opening was assessed after cervical manipulation. In five of the nine studies on cervical ROM a positive effect was reported, whereas the remaining four studies did not show improvement. None of the three studies of the lumbar spine showed an effect of SMT on lumbar ROMs and one study of sacroiliac manipulation reported no effect on the ROM of the hip joint. In relation to the quality score, the seven highest ranked studies, showed significant positive effects of SMT on ROM. Continuing down the list, the other studies reported no significant differences in the outcomes between groups. Conclusion SMT seems sometimes to have a small effect on ROM, at least in the cervical spine. Further research

  16. Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Agra Cavalcante-Silva

    2014-09-01

    Full Text Available In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p. pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs.

  17. Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index.

    Science.gov (United States)

    Scivoletto, G; Bonavita, J; Torre, M; Baroncini, I; Tiberti, S; Maietti, E; Laurenza, L; China, S; Corallo, V; Guerra, F; Buscaroli, L; Candeloro, C; Brunelli, E; Catz, A; Molinari, M

    2016-06-01

    Retrospective observational study. The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. Two spinal units in Italy. Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI-ARMI score rehabilitation. The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential.

  18. Effect of Spinal Anaesthesia on Hearing Threshold | Lasisi | East ...

    African Journals Online (AJOL)

    Background: Hearing loss following spinal anaesthesia is a known yet uncommonly reported complication. This study was aimed at determining the incidence and type of hearing loss (HL) following spinal anaesthesia (SA) and the relationship with the size of spinal needle. Methods: A prospective study of patients ...

  19. Effects of pre-treatment with amantadine on morphine induced antinociception during second phase formalin responses in rats

    NARCIS (Netherlands)

    Snijdelaar, D.G.; Rijn, C.M. van; Vinken, P.; Meert, T.F.

    2005-01-01

    The clinically available NMDA-receptor antagonist drug, amantadine, has been shown to result in morphine sparing effects in humans after surgery. However, no data are available to describe the exact form of interaction. The present study aims to profile the possible effects of amantadine (0, 12.5,

  20. Effects of pre-treatment with amantadine on morphine induced antinociception during second phase formalin responses in rats.

    NARCIS (Netherlands)

    Snijdelaar, D.G.; Rijn, C.M. van; Vinken, P.; Meert, T.F.

    2005-01-01

    The clinically available NMDA-receptor antagonist drug, amantadine, has been shown to result in morphine sparing effects in humans after surgery. However, no data are available to describe the exact form of interaction. The present study aims to profile the possible effects of amantadine (0, 12.5,

  1. Effect of Spinal Manipulative Therapy on the Singing Voice.

    Science.gov (United States)

    Fachinatto, Ana Paula A; Duprat, André de Campos; Silva, Marta Andrada E; Bracher, Eduardo Sawaya Botelho; Benedicto, Camila de Carvalho; Luz, Victor Botta Colangelo; Nogueira, Maruan Nogueira; Fonseca, Beatriz Suster Gomes

    2015-09-01

    This study investigated the effect of spinal manipulative therapy (SMT) on the singing voice of male individuals. Randomized, controlled, case-crossover trial. Twenty-nine subjects were selected among male members of the Heralds of the Gospel. This association was chosen because it is a group of persons with similar singing activities. Participants were randomly assigned to two groups: (A) chiropractic SMT procedure and (B) nontherapeutic transcutaneous electrical nerve stimulation (TENS) procedure. Recordings of the singing voice of each participant were taken immediately before and after the procedures. After a 14-day period, procedures were switched between groups: participants who underwent SMT on the first day were subjected to TENS and vice versa. Recordings were subjected to perceptual audio and acoustic evaluations. The same recording segment of each participant was selected. Perceptual audio evaluation was performed by a specialist panel (SP). Recordings of each participant were randomly presented thus making the SP blind to intervention type and recording session (before/after intervention). Recordings compiled in a randomized order were also subjected to acoustic evaluation. No differences in the quality of the singing on perceptual audio evaluation were observed between TENS and SMT. No differences in the quality of the singing voice of asymptomatic male singers were observed on perceptual audio evaluation or acoustic evaluation after a single spinal manipulative intervention of the thoracic and cervical spine. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  2. Pro-resolution, protective and anti-nociceptive effects of a cannabis extract in the rat gastrointestinal tract.

    Science.gov (United States)

    Wallace, J L; Flannigan, K L; McKnight, W; Wang, L; Ferraz, J G P; Tuitt, D

    2013-04-01

    Cannabis is widely used for treating a number of gastrointestinal ailments, but its use is associated with several adverse effects, particularly when the route of administration is via smoking. In the present study, we tested the effects (in rats) of a simple extract of medicinal cannabis (called "MFF") for its ability to promote resolution of colitis, to prevent gastric damage induced by naproxen, and to reduce gastric distention-induced visceral pain. Intracolonic, but not oral administration of MFF dose-dependently reduced the severity of hapten-induced colitis, an effect not reduced by pretreatment with antagonists of CB1 or CB2 receptors. Significant improvement of symptoms (diarrhea, weight loss) and healing of ulcerated tissue was evident with MFF treatment at doses that did not produce detectable urinary levels of 9-Δ-tetrahydrocannabinol (THC). MFF increased colonic hydrogen sulfide synthesis in healthy rats, but not in rats with colitis, and had no effect on colonic prostaglandin E2 synthesis. Orally, but not systemically administered MFF dose-dependently reduced the severity of naproxen-induced gastric damage, and a CB1 antagonist reversed this effect. MFF prevented gastric distention-induced visceral pain via a CB2-dependent mechanism. These results demonstrate that a simple extract of medicinal cannabis can significantly enhance resolution of inflammation and injury, as well as prevent injury, in the gastrointestinal tract. Interestingly, different cannabinoid receptors were involved in some of the effects. MFF may serve as the basis for a simple preparation of cannabis that would produce beneficial effects in the GI tract with reduced systemic toxicity.

  3. Antinociceptive Activity of an Ethanol Extract of Justicia spicigera.

    Science.gov (United States)

    Zapata-Morales, Juan Ramón; Alonso-Castro, Angel Josabad; Domínguez, Fabiola; Carranza-Álvarez, Candy; Castellanos, Luis Manuel Orozco; Martínez-Medina, Rosa María; Pérez-Urizar, José

    2016-06-01

    Preclinical Research The aim of the present study was to evaluate the antinociceptive and sedative activity of an ethanol extract of Justicia spicigera an evergreen used in Mexican traditional medicine for the relief of pain, wounds, fever and inflammation. At 200 mg/kg po, the maximum dose examined, the ethanol extract of J. spicigera (JSE) had analgesic activity in mice in the acetic acid writhing test, the second phase of the formalin test and the tail flick test that was similar in efficacy to the NSAID, naproxen (150 mg/kg po). JSE was inactive in the hot plate test and and the ketamine-induced sleeping time test; it had no sedative effects. These results show that the ethanol extract from the leaves of J. spicigera has antinociceptive effects in mice without inducing sedation. Drug Dev Res 77 : 180-186, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Class I antiarrhythmic drugs produced a spinal anesthetic effect in rats.

    Science.gov (United States)

    Huang, Kuo-Lun; Chu, Chin-Chen; Cheng, Kuang-I; Wang, Jhi-Joung; Yeh, Mou-Yung

    2011-11-14

    Class I antiarrhythmic drugs are commonly used to treat cardiac rhythm disorders. Some of those drugs were recently reported to have both a cutaneous analgesic and a neural blocking effect. We evaluated whether these drugs have a spinal anesthetic effect. Three Class I antiarrhythmic drugs (class IA: quinidine, IB: mexiletine, and IC: flecainide) were tested. After they had been intrathecally injected in rats, the potencies and durations of these drugs on spinal anesthesia were recorded. Bupivacaine, a commonly used local anesthetic, and 5% dextrose solution were used as controls. Bupivacaine, flecainide, quinidine, and mexiletine produced a dose-related spinal blockade of motor function, proprioception, and nociception, but dextrose solution produced no spinal anesthetic effect. The descending order of potency was bupivacaine>flecainide>quinidine>mexiletine (pantiarrhythmic drugs produced a dose-related spinal anesthetic effect. These drugs may be potential candidates for developing new local anesthetics. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis, and possible involvement of the adenosine system

    OpenAIRE

    Mei-Liang Wang; Gang Yu; Shou-Pu Yi; Feng-Ying Zhang; Zhi-Tong Wang; Bin Huang; Rui-Bin Su; Yan-Xing Jia; Ze-Hui Gong

    2015-01-01

    Incarvillea sinensis is a Bignoniaceae plant used to treat rheumatism and relieve pain in traditional Chinese medicine. As a major component of I. sinensis, incarvillateine has shown analgesic activity in mice formalin tests. Using a series of animal models, this study further evaluated the effects of incarvillateine against acute, inflammatory, and neuropathic pain. Incarvillateine (10 or 20?mg/kg, i.p.) dose-dependently attenuated acetic acid-induced writhing, but did not affect thermal thr...

  6. The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury

    National Research Council Canada - National Science Library

    Lin, Chia-Ching; Lai, Sih-Rong; Shao, Yu-Han; Chen, Chun-Lin; Lee, Kun-Ze

    2017-01-01

    Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading...

  7. Dose-volume effects in the rat cervical spinal cord after proton irradiation

    NARCIS (Netherlands)

    Bijl, HP; van Luijk, P; Coppes, RP; Schippers, JM; Konings, AWT; van der Kogel, AJ

    2002-01-01

    Purpose: To estimate dose-volume effects in the rat cervical spinal cord with protons. Methods and Materials: Wistar rats were irradiated on the cervical spinal cord with a single fraction of unmodulated protons (150-190 MeV) using the shoot through method, which employs the plateau of the

  8. Seat height : effects on submaximal hand rim wheelchair performance during spinal cord injury rehabilitation

    NARCIS (Netherlands)

    van der Woude, Lucas H V; Bouw, Arianne; van Wegen, Joeri; van As, Harry; Veeger, DirkJan (H. E. J.); de Groot, Sonja

    OBJECTIVE: To evaluate the effects of wheelchair seat height on wheeling efficiency and technique during rehabilitation in subjects with a spinal cord injury. DESIGN: Laboratory-based study. SUBJECTS: Twelve persons with spinal cord injury (age range 19-77 years, lesion level: C5/C6-L2; 7 men; 8

  9. The effect of body position and axial load on spinal canal morphology: an MRI study of central spinal stenosis

    DEFF Research Database (Denmark)

    Madsen, Rasmus; Jensen, Tue Secher; Pope, Malcolm

    2007-01-01

    and DCSA are well documented. However, the effects of axial loading, achieved by upright standing or by a compression device, are still unclear. METHODS: Patients with lumbar spinal stenosis were examined in 2 separate studies, including 16 and 20 patients, respectively. In section 1, magnetic resonance......STUDY DESIGN: A method comparison study. OBJECTIVE: To investigate the effect of body position and axial load of the lumbar spine on disc height, lumbar lordosis, and dural sac cross-sectional area (DCSA). SUMMARY OF BACKGROUND DATA.: The effects of flexion and extension on spinal canal diameters...... imaging (MRI) scans were performed during upright standing and supine positions with and without axial load. In section 2, MRI scans were performed exclusively in supine positions, one with flexion of the lumbar spine (psoas-relaxed position), an extended position (legs straight), and an extended position...

  10. Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain

    Directory of Open Access Journals (Sweden)

    Ogawa Tomoyo

    2011-05-01

    Full Text Available 1. Abstract Background Cyclic phosphatidic acid (cPA is a structural analog of lysophosphatidic acid (LPA, but possesses different biological functions, such as the inhibition of autotaxin (ATX, an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA, a chemically stable cPA analog, on acute and chronic pain. Results (1 The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3 In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4 In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5 In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction. Conclusions Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.

  11. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception.

    Science.gov (United States)

    Katsuyama, S; Mizoguchi, H; Kuwahata, H; Komatsu, T; Nagaoka, K; Nakamura, H; Bagetta, G; Sakurada, T; Sakurada, S

    2013-05-01

    β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis. The present study investigated the contribution of peripheral cannabinoid (CB) and opioid systems in the antinociception produced by intraplantar (i.pl.) injection of BCP. The interaction between peripheral BCP and morphine was also examined. The antinociceptive effect of i.pl. BCP was assayed by the capsaicin tests in mice. Antagonists for CB and opioid receptors, and antisera against β-endorphin were injected peripherally prior to i.pl. injection of BCP. Morphine in combination with BCP was injected subcutaneously or intrathecally. The i.pl. injection of BCP dose-dependently attenuated capsaicin-induced nociceptive response. The antinociceptive effect produced by BCP was prevented by pretreatment with AM630, a selective CB2 receptor antagonist, but not by AM251, a selective CB1 receptor antagonist. Pretreatment with naloxone, an opioid receptor antagonist, and β-funaltrexamine, a selective μ-opioid receptor antagonist, reversed the antinociceptive effect of BCP. Pretreatment with naloxone methiodide, a peripherally acting antagonist for opioid receptors and antisera against β-endorphin, resulted in a significant antagonizing effect on BCP-induced antinociception. Morphine-induced antinociception was increased by a low dose of BCP. The increased effect of morphine in combination with BCP was antagonized significantly by pretreatment with naloxone. The present results demonstrate that antinociception produced by i.pl. BCP is mediated by activation of CB2 receptors, which stimulates the local release from keratinocytes of the endogenous opioid β-endorphin. The combined injection of morphine and BCP may be an alternative in treating chemogenic pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

  12. The effect of three-dimensional geometrical changes during adolescent growth on the biomechanics of a spinal motion segment

    NARCIS (Netherlands)

    Homminga, J.; Hekman, E. E. G.; Veldhuizen, A. G.; Verkerke, G. J.; Meijer, G.

    2010-01-01

    During adolescent growth, vertebrae and intervertebral discs undergo various geometrical changes. Although such changes in geometry are well known, their effects on spinal stiffness remains poorly understood. However, this understanding is essential in the treatment of spinal abnormalities during

  13. Neural effects of muscle stretching on the spinal reflexes in multiple lower-limb muscles.

    Science.gov (United States)

    Masugi, Yohei; Obata, Hiroki; Inoue, Daisuke; Kawashima, Noritaka; Nakazawa, Kimitaka

    2017-01-01

    While previous studies have shown that muscle stretching suppresses monosynaptic spinal reflex excitability in stretched muscles, its effects on non-stretched muscles is still largely unknown. The purpose of this study was to examine the effects of muscle stretching on monosynaptic spinal reflex in non-stretched muscles. Ten healthy male subjects participated in this study. Muscle stretching of the right triceps surae muscle was performed using a motor torque device for 1 minute. Three different dorsiflexion torques (at approximately 5, 10, and 15 Nm) were applied during muscle stretching. Spinal reflexes evoked by transcutaneous spinal cord stimulation were recorded in both the lower-limb muscles before, during, and at 0 and 5 min following muscle stretching. The amplitudes of the spinal reflexes in both the stretched and non-stretched muscles in the right (ipsilateral) leg were smaller during stretching compared to before, and at 0 and 5 min after stretching. Furthermore, the degree of reduction in the amplitude of the spinal reflexes in the right (ipsilateral) leg muscles increased significantly as the dorsiflexion torque (i.e., stretching of the right triceps surae muscles) increased. In contrast, reduction in the amplitude of the spinal reflexes with increasing dorsiflexion torque was not seen in the left (contralateral) leg muscles. Our results clearly indicate that muscle stretching has inhibitory effects on monosynaptic spinal reflexes, not only in stretched muscles, but also in non-stretched muscles of the ipsilateral leg.

  14. Low doses of urethane effectively inhibit spinal seizures evoked by sudden cooling of toad isolated spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Pina-crespo, J.C.; Dalo, N.L. (Univ. Centroccidental Lisandro Alvarado, Barquisimeto (Venezuela))

    1992-01-01

    The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91[plus minus]3 sec exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction. The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphaticaly with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockage of seizures was seen after doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested.

  15. Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheral β-Adrenoceptors

    Directory of Open Access Journals (Sweden)

    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.

  16. Protective Effects of Two Constituents of Chinese Herbs on Spinal ...

    African Journals Online (AJOL)

    Spinal motor neurons (SMNs) from rat spinal cords were obtained and divided into five groups with 10 wells in each group. In control group, SMNs suffered no injury under normal oxygen; in hypoxia- inducible (HI) group, SMNs suffered injury from hypoxia; in Gin group, 37.5μg/ml Gin were used before 24 hrs of hypoxia; ...

  17. Spinal SIRT1 activation attenuates neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    Haijun Shao

    Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

  18. Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis.

    Science.gov (United States)

    Abdelhalim, Abeer; Karim, Nasiara; Chebib, Mary; Aburjai, Talal; Khan, Imran; Johnston, Graham A R; Hanrahan, Jane

    2015-01-01

    Rosmarinus officinalis, traditionally known as rosemary, has been widely used in traditional medicines and has long been known as the herb of remembrance. However, few studies have investigated the effects of non-volatile components of rosemary on central nervous system function. Fractionation of R. officinalis led to the isolation of salvigenin, rosmanol and cirsimaritin, which were investigated in mouse models of acute toxicity, antinociception (tail immersion and hot plate tests), depression (tail suspension and forced swim tests) and anxiety (elevated plus maze and light/dark box paradigms). Rosmanol, cirsimaritin and salvigenin were not found to exhibit any signs of acute toxicity (50-200 mg/kg), but elicited antinociceptive, antidepressant and anxiolytic activities. Rosmanol, cirsimaritin and salvigenin, all previously shown to have biphasic modulation of GABAA receptors, demonstrated CNS activity in mouse models of antinociception, antidepressant and anxiolysis. The anxiolytic activity of all three compounds was not ameliorated by flumazenil, but was inhibited by pentylenetetrazol, suggesting a mode of action via GABAA receptors at a site other than the high affinity benzodiazepine binding site. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  19. Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira).

    Science.gov (United States)

    Thomazzi, S M; Silva, C B; Silveira, D C R; Vasconcellos, C L C; Lira, A F; Cambui, E V F; Estevam, C S; Antoniolli, A R

    2010-02-03

    Bowdichia virgilioides Kunth (Leguminosae Papilonoideae) is a plant with anti-inflammatory activity used in folk medicine. The importance of this plant promoted its inclusion in Brazilian Pharmacopoeia. In order to evaluate the actions of this plant, studies were performed on antinociceptive and anti-inflammatory activities. The aqueous extracts (AE) of Bowdichia virgilioides inner bark and leaves were used at 100, 200, and 400mg/kg. Antinociceptive activity of plant extract was evaluated by writhing, hot-plate and formalin tests. Anti-inflammatory activity was evaluated using paw oedema and peritonitis methods. Oral treatment with the AE of inner bark or leaves elicited inhibitory activity (P400mg/kg, and reduced the formalin effect at the second-phase (200 and 400mg/kg, P400mg/kg (P<0.05), and by the reference compounds aspirin (P<0.001) and dexamethasone (P<0.001), respectively. The AE of Bowdichia virgilioides shows antinociceptive and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  20. The Study of Oral Clonidine Effect in Duration of Spinal Anesthesia with Lidocaine and Its Complications

    Directory of Open Access Journals (Sweden)

    M. Baalbaki

    2003-07-01

    Full Text Available There are many kinds of intervention to prolong the duration of spinal anesthesia which one of them is preoperation oral drugs. The purpose of this study was determination of clonidine effects in duration of spinal anesthesia and its complications. This study was a double - blinded randomized controlled clinical trial in 40-60 years old males of Mobasher and Ekbatan hospitals in Hamadan. In this study there were 40 cases candidated for spinal anesthesia and we divided them to 2 groups i.e. test and control then the results were recorded on questionnaire sheets. The test cases were prescribed 0.2 mg clonidine P.O. preoperatively and their duration of spinal anesthesia prolonged 11 minutes averagely and decreased its complications related to control prescribed placebo. Hence , the result showed preparation oral clonidine prolongs the duration of spinal anesthesia and decreases its complications like hypotention , nausea and vomiting.

  1. The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation.

    Science.gov (United States)

    Cuellar, Carlos A; Mendez, Aldo A; Islam, Riazul; Calvert, Jonathan S; Grahn, Peter J; Knudsen, Bruce; Pham, Tuan; Lee, Kendall H; Lavrov, Igor A

    2017-01-01

    In this study, the neuroanatomy of the swine lumbar spinal cord, particularly the spatial orientation of dorsal roots was correlated to the anatomical landmarks of the lumbar spine and to the magnitude of motor evoked potentials during epidural electrical stimulation (EES). We found that the proximity of the stimulating electrode to the dorsal roots entry zone across spinal segments was a critical factor to evoke higher peak-to-peak motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher impact on motor evoked responses than rostro-caudal shift of electrode from segment to segment. Based on anatomical measurements of the lumbar spine and spinal cord, significant differences were found between L1-L4 to L5-L6 segments in terms of spinal cord gross anatomy, dorsal roots and spine landmarks. Linear regression analysis between intersegmental landmarks was performed and L2 intervertebral spinous process length was selected as the anatomical reference in order to correlate vertebral landmarks and the spinal cord structures. These findings present for the first time, the influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots. These results are critical to consider as spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translate into clinical practice.

  2. The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation

    Directory of Open Access Journals (Sweden)

    Carlos A. Cuellar

    2017-09-01

    Full Text Available In this study, the neuroanatomy of the swine lumbar spinal cord, particularly the spatial orientation of dorsal roots was correlated to the anatomical landmarks of the lumbar spine and to the magnitude of motor evoked potentials during epidural electrical stimulation (EES. We found that the proximity of the stimulating electrode to the dorsal roots entry zone across spinal segments was a critical factor to evoke higher peak-to-peak motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher impact on motor evoked responses than rostro-caudal shift of electrode from segment to segment. Based on anatomical measurements of the lumbar spine and spinal cord, significant differences were found between L1-L4 to L5-L6 segments in terms of spinal cord gross anatomy, dorsal roots and spine landmarks. Linear regression analysis between intersegmental landmarks was performed and L2 intervertebral spinous process length was selected as the anatomical reference in order to correlate vertebral landmarks and the spinal cord structures. These findings present for the first time, the influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots. These results are critical to consider as spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translate into clinical practice.

  3. The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation

    Science.gov (United States)

    Cuellar, Carlos A.; Mendez, Aldo A.; Islam, Riazul; Calvert, Jonathan S.; Grahn, Peter J.; Knudsen, Bruce; Pham, Tuan; Lee, Kendall H.; Lavrov, Igor A.

    2017-01-01

    In this study, the neuroanatomy of the swine lumbar spinal cord, particularly the spatial orientation of dorsal roots was correlated to the anatomical landmarks of the lumbar spine and to the magnitude of motor evoked potentials during epidural electrical stimulation (EES). We found that the proximity of the stimulating electrode to the dorsal roots entry zone across spinal segments was a critical factor to evoke higher peak-to-peak motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher impact on motor evoked responses than rostro-caudal shift of electrode from segment to segment. Based on anatomical measurements of the lumbar spine and spinal cord, significant differences were found between L1-L4 to L5-L6 segments in terms of spinal cord gross anatomy, dorsal roots and spine landmarks. Linear regression analysis between intersegmental landmarks was performed and L2 intervertebral spinous process length was selected as the anatomical reference in order to correlate vertebral landmarks and the spinal cord structures. These findings present for the first time, the influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots. These results are critical to consider as spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translate into clinical practice. PMID:29075183

  4. Bioassay-guided evaluation of Dioscorea villosa - an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach

    National Research Council Canada - National Science Library

    Lima, Claudio Moreira; Lima, Adriana Karla; Melo, Marcelia G Dória; Serafini, Mairim Russo; Oliveira, Dênisson Lima; de Almeida, Enrik Barbosa; Barreto, Rosana Souza Siqueira; Nogueira, Paulo Cesar de Lima; Moraes, Valéria Regina de Souza; Oliveira, Edica Ramone Andrade; de Albuquerque, Jr, Ricardo Luiz Cavalcanti; Quintans-Júnior, Lucindo J; Araújo, Adriano Antunes Souza

    2013-01-01

    .... In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days...

  5. Involvement of Cholinergic and Opioid System in γ-Terpinene-Mediated Antinociception

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    Flávia Franceli de Brito Passos

    2015-01-01

    Full Text Available The literature shows that the monoterpenes are great candidates for the development of new drugs for the treatment of various pathological processes, including painful conditions. The gamma terpinene (γ-TPN is a monoterpene present in plant species that have multiple pharmacological properties and has structural similarity to antinociceptive monoterpenes, such as limonene and alpha-phellandrene. The γ-TPN molecular mass was evaluated by mass spectrometry and showed a pseudomolecular ion with m/z 137.0 Da. The animals did not present any signs of acute toxicity at 2 g/kg, p.o. γ-TPN (1.562 to 50 mg/kg, p.o. showed an antinociceptive effect in the formalin, capsaicin, and glutamate tests. γ-TPN has antinociceptive action when administered by others routes in glutamate test. To eliminate a possible sedative effect of γ-TPN, the open field and rota-rod test were conducted and the γ-TPN did not show muscle relaxant activity or central depressant effect. To investigate the mechanisms of action, the animals were pretreated with naloxone, glibenclamide, atropine, mecamylamine, or L-arginine in the glutamate test. γ-TPN antinociception was inhibited in the presence of naloxone, glibenclamide, atropine, and mecamylamine. The results suggest that the γ-TPN (p.o. produced antinociceptive effect in models of chemical nociception through the cholinergic and opioid systems involvement.

  6. Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to opioidergic activation.

    Science.gov (United States)

    Veloso, Clarice de Carvalho; Rodrigues, Vanessa Gregório; Ferreira, Renata Cristina Mendes; Duarte, Lucienir Pains; Klein, Andre; Duarte, Igor Dimitri; Romero, Thiago Roberto Lima; Perez, Andrea de Castro

    2014-11-01

    Plants belonging to the genus Maytenus are routinely used in folk medicine for the treatment of pain diseases. Our previous phytochemical study of the roots of Maytenus imbricata resulted in the isolation and characterization of tingenone, a pentacyclic triterpene. Natural triterpenoids are of growing interest because they have several biological activities, including analgesic properties. The present study assessed the involvement of the opiodergic pathway in the tingenone-induced antinociceptive effect against hyperalgesia induced by prostaglandin E2 (2 µg) in the peripheral pathway. We evaluated the effect of several antagonists to opioid receptors using the mouse paw pressure test. Tingenone administered into the right hind paw induced a local antinociceptive effect that was antagonized by naloxone, a nonselective antagonist to opioid receptors. Clocinnamox, naltrindole, and nor-binaltorphimine are selective antagonists to µ, δ, and κ receptors, respectively, which reverted the peripheral antinociception induced by tingenone. Bestatine acts as an inhibitor of aminopeptidase, an enzyme that degrades endogenous opioid peptides, and was shown to intensify the antinociceptive effect of tingenone. The results suggest that the opioidergic system participates in the peripheral antinociception induced by tingenone. Georg Thieme Verlag KG Stuttgart · New York.

  7. Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

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    Renata Cristina Mendes Ferreira

    2017-01-01

    Full Text Available Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg. Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2 injection. Results. Aripiprazole (100 μg/paw injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw, a nonselective opioid receptor antagonist. The role of μ-, δ-, and κ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw, naltrindole (15, 30, and 60 μg/paw, and nor-binaltorphimine (200 μg/paw, respectively. The data indicated that only the δ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg, an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw aripiprazole-induced peripheral antinociception. Conclusion. The results suggest the participation of the opioid system via δ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

  8. In vivo antinociceptive and muscle relaxant activity of leaf and bark of Buddleja asiatica L.

    Science.gov (United States)

    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.

  9. Doxepin Has a Potent and Long-Acting Spinal Anesthetic Effect in Rats

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    Bor-Chin Cheng

    2006-02-01

    Full Text Available Doxepin, a tricyclic antidepressant, was recently found to be effective in the treatment of various acute and chronic painful conditions. However, the mechanism of its actions was not clear, especially when involving the spine. The aim of our study was to evaluate the spinal anesthetic effect of doxepin. Two commonly used traditional local anesthetics, bupivacaine and lidocaine, were used as controls. The potencies and durations of the drugs' action were evaluated in male Sprague-Dawley rats. We found that intrathecally administered doxepin, like bupivacaine and lidocaine, produced dose-related spinal anesthetic effects on motor activity, proprioception, and nociception. Among the three drugs, doxepin produced spinal anesthetic effects in rats more potent than that of lidocaine (p < 0.001, in each comparison and longer than that of bupivacaine and lidocaine (p < 0.001, in each comparison. The spinal activity of doxepin may provide some explanation of its clinical effect in pain management.

  10. Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey?

    Directory of Open Access Journals (Sweden)

    Nana Tsiklauri

    2014-01-01

    Full Text Available Emotional distress is the most undesirable feature of painful experience. Numerous studies have demonstrated the important role of the limbic system in the affective-motivational component of pain. The purpose of this paper was to examine whether microinjection of nonsteroidal anti-inflammatory drugs (NSAIDs, Clodifen, Ketorolac, and Xefocam, into the dorsal hippocampus (DH leads to the development of antinociceptive tolerance in male rats. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the tail-flick (TF and hot plate (HP tests compared to controls treated with saline into the DH. Subsequent tests on consecutive three days, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and posttreatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our data indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

  11. Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model

    Directory of Open Access Journals (Sweden)

    Suk-Yun Kang

    2015-07-01

    Full Text Available The administration of diluted bee venom (DBV into an acupuncture point has been utilized traditionally in Eastern medicine to treat chronic pain. We demonstrated previously that DBV has a potent anti-nociceptive efficacy in several rodent pain models. The present study was designed to examine the potential anti-nociceptive effect of repetitive DBV treatment in the development of below-level neuropathic pain in spinal cord injury (SCI rats. DBV was applied into the Joksamli acupoint during the induction and maintenance phase following thoracic 13 (T13 spinal hemisection. We examined the effect of repetitive DBV stimulation on SCI-induced bilateral pain behaviors, glia expression and motor function recovery. Repetitive DBV stimulation during the induction period, but not the maintenance, suppressed pain behavior in the ipsilateral hind paw. Moreover, SCI-induced increase in spinal glia expression was also suppressed by repetitive DBV treatment in the ipsilateral dorsal spinal cord. Finally, DBV injection facilitated motor function recovery as indicated by the Basso–Beattie–Bresnahan rating score. These results indicate that the repetitive application of DBV during the induction phase not only decreased neuropathic pain behavior and glia expression, but also enhanced locomotor functional recovery after SCI. This study suggests that DBV acupuncture can be a potential clinical therapy for SCI management.

  12. Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds

    Science.gov (United States)

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

    2015-01-01

    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. PMID:26273315

  13. Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds

    Directory of Open Access Journals (Sweden)

    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.

  14. Effectiveness of dietary supplements in spinal cord injury subjects.

    Science.gov (United States)

    Navarrete-Opazo, Angela; Cuitiño, Pilar; Salas, Inés

    2017-04-01

    Individuals with spinal cord injury (SCI) consume more dietary supplements than the general population. However, there is limited information regarding the clinical effectiveness of dietary supplements in SCI population. To systematically review the effectiveness of dietary supplements for the prevention or treatment of health-related conditions associated with SCI. Randomized or non-randomized controlled clinical trials were selected, comparing the effect of any dose and form of a dietary supplement (defined by the Dietary Supplement Health and Education Act), with either no treatment, placebo, or other medication. Data Sources included the Cochrane Database, DARE, LILACS, CINAHL, EMBASE, MEDLINE, OTSeeker, PEDro, PsycINFO, SpeechBITE, ScienceDirect, Scopus, clinicaltrials.gov, Google Scholar, and OpenGrey. Two reviewers independently classified articles from January 1970 through October 2015, and 18 articles were selected. Due to the heterogeneity of outcome measures across studies, a meta-analysis was not conducted. However, high-quality evidence showed that cranberry supplementation is not effective for prevention of urinary tract infections (UTIs) in SCI. Moderate-quality evidence supported a beneficial effect of vitamin D, alpha-lipoic acid, and omega-3 supplementation, although replication of results is needed. There were conflicting results for the effect of creatine supplementation on improvement of motor outcomes. Low-quality evidence does not permit assessment of the effectiveness of melatonin, whey protein, vitamin C, and Chinese herb in SCI. There is sufficient data suggesting that cranberry supplementation is ineffective for prevention of UTIs in individuals with SCI. There is insufficient data to support or refute the use of any other dietary supplement in individuals with SCI. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Anti-nociceptive and anti-inflammatory activities of the extracts of Stauntonia chinensis.

    Science.gov (United States)

    Ying, Chen; Ning, Wu; Ying, Liu; Hao, Gao; Hua-Jin, Dong; Rui-Bin, Su; Xin-Sheng, Yao; Jin, Li

    2014-09-01

    The aim of this investigation was to study the anti-nociceptive and anti-inflammatory activities of Stauntonia chinensis (S. chinensis) and the possible action mechanisms of effective fractions. The anti-nociceptive and anti-inflammatory activities of S. chinensis extracts, including the 60% EtOH extract (YMG), the n-BuOH extract (YMGB) and the aqueous residue (YMGW) of YMG, and the fractions from YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-induced writhing test and the rat formalin test. The effect of these extracts on the PGE2 production was tested as well. In the mouse acetic acid-induced writhing test and the rat formalin test, YMGW and YMGB displayed anti-nociceptive and anti-inflammatory activities, suggesting that they were the active ingredients of YMG. Among the fractions isolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main active ingredients producing anti-nociceptive activity and YMGB3, YMGB5, YMGB6 and YMGB7 were the main active ingredients producing anti-inflammatory activity. Additionally, YMGW, YMGB and its separations reduced the production of PGE2, which might be the mechanism of them producing anti-inflammatory activity. These results demonstrated the active ingredients of S. chinensis producing anti-nociceptive and anti-inflammatory activities, which is valuable to validate the substance basis of S. chinensis's pharmacological actions.

  16. Antinociceptive and anti-inflammatory activities of an aqueous extract of Chiliotrichum diffusum

    Directory of Open Access Journals (Sweden)

    Sandra M. Alcalde Bahamonde

    2013-08-01

    Full Text Available The flowers of the Chiliotrichum diffusum (G. Forst. Kuntze, Asteraceae, have long been used in traditional medicine and rituals. In this study, the anti-inflammatory and antinociceptive activities of a decoction of the flowers were evaluated and a phytochemical analysis was performed by HPLC-DAD. In order to evaluate the antinociceptive activity, the acetic acid-induced abdominal writhing and hot plate tests were used. The anti-inflammatory activity was evaluated using carrageenaninduced rat paw oedema. The decoction induced a significant anti-inflammatory effect (inhibition of 56.0% at 3 h and produced significant inhibition on nociception in the acetic acid test (ED50 35 mg/kg i.p.; ED50 709 mg/kg p.o.. In the hot plate test, the antinociceptive activity of the extract employed at 500 mg/kg i.p. was significantly suppressed by pretreatment with naloxone (5 mg/kg. HPLC analysis showed the presence of chlorogenic acid, caffeic acid, hyperoside, isoquercitrin, quercitrin, afzelin, quercetin, apigenin and kaempferol. The decoction of C. diffusum proved to have antinociceptive and anti-inflammatory effects that may be related to the presence of the flavones, flavonols and phenolic acids identified. The opiod system seems to be involved in the mechanism of antinociception of the extract.

  17. Effect of spine hardware on small spinal stereotactic radiosurgery dosimetry

    Science.gov (United States)

    Wang, Xin; Yang, James N.; Li, Xiaoqiang; Tailor, Ramesh; Vassilliev, Oleg; Brown, Paul; Rhines, Laurence; Chang, Eric

    2013-10-01

    Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose perturbation from a titanium rod 5 mm in diameter in various small fields range from 2 × 2 to 5 × 5 cm2. The results showed that the rod increased the dose to water by ˜6% at the water-rod interface because of electron backscattering and decreased the dose by ˜7% in the shadow of the rod because of photon attenuation. The Pinnacle3 treatment planning system calculations matched the MC results at the depths more than 1 cm past the rod when the correct titanium density of 4.5 g cm-3 was used, but significantly underestimated the backscattering dose at the water-rod interface. A CT-density table with a top density of 1.82 g cm-3 (cortical bone) is a practical way to reduce the dosimetric error from the artifacts by preventing high density assignment to them, but can underestimates the attenuation by the titanium rod by 6%. However, when multi-beam with intensity modulation is used in actual patient spinal stereotactic radiosurgery treatment, the dosimetric effect of assigning 4.5 instead of 1.82 g cm-3 to titanium implants is complicated. It ranged from minimal effect to 2% dose difference affecting 15% target volume in the study. When hardware is in the beam path, density override to the titanium hardware is recommended.

  18. Antinociceptive properties of conocarpan and orientin obtained from Piper solmsianum C. DC. var. solmsianum (Piperaceae).

    Science.gov (United States)

    Da Silva, Rosi Zanoni; Yunes, Rosendo Augusto; de Souza, Márcia Maria; Delle Monache, Franco; Cechinel-Filho, Valdir

    2010-10-01

    The antinociceptive properties of some fractions and two pure compounds, conocarpan and orientin, obtained from P. solmsianum leaves were investigated in several models of pain in mice. The results indicated that this plant exhibits a promising antinociceptive profile, as it produces active principles which are several times more active than some reference drugs used for comparison. The main compound tested, orientin, caused potent and dose-dependent effects against acetic acid-induced writhing and capsaicin- and glutamate-induced nociception, being more effective against the first one, with an ID(50) value of 6.5 mg/kg (14.5 micromol/kg). Orientin was about 20-fold more potent than acetylsalicylic acid and 3.5-fold more active than indomethacin. The antinociceptive effects of this plant may be attributed, at least partially, to the presence of conocarpan and, in particular, to the flavonoid orientin.

  19. Direct spinal effect of intrathecal and extradural midazolam on visceral noxious stimulation in rabbits

    DEFF Research Database (Denmark)

    Crawford, M E; Jensen, F M; Toftdahl, D B

    1993-01-01

    was demonstrated using transcutaneous electrical stimulation in the areas of the neck and the lower back. The effect of intrathecal midazolam 62.5 microrgrams kg-1 was restricted to the lumbar region, demonstrating a selective action on the spinal cord. Thus extradural and intrathecal midazolam produced a dose......-dependent effect on the reflex response to visceral distension in rabbits. This effect is caused by a direct spinal action on benzodiazepine receptors in the spinal cord.......We measured alterations in a noxious visceromotor reflex in rabbits subjected to intestinal distension, after i.m., extradural or intrathecal injection of midazolam or saline. Spinal catheters were inserted and tunnelled surgically and the animals allowed to recover for 2 weeks. A balloon catheter...

  20. The effect of Sativex in neuropathic pain and spasticity in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Hansen, Rikke Bod Middelhede; Johansen, Inger Lauge

    2014-01-01

    often receive incomplete relief from present available and recommended treatment. Cannabinoids has shown efficacy on both neuropathic pain and spasticity in patients with spinal cord injury, but the studies one the topic has been too small to make a general conclusion for patients with spinal cord...... injury. Aims: To investigate the effect of Sativex (cannabinoid agonist given as an oral mucosal spray), on neuropathic pain and spasticity in patients with spinal cord injury. Methods: A randomized, double-blind, placebo-controlled crossover study. We will include 30 patients with neuropathic pain...

  1. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  2. The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.

    Science.gov (United States)

    Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

    2014-02-01

    Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB₁ and CB₂ cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB₁ receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB₁ receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Activity-Guided Isolation of Bioactive Constituents with Antinociceptive Activity from Muntingia calabura L. Leaves Using the Formalin Test

    OpenAIRE

    Mohamad Yusof, Mohd. Izwan; Salleh, Mohd. Zaki; Lay Kek, Teh; Ahmat, Norizan; Nik Azmin, Nik Fatini; Zakaria, Zainul Amiruddin

    2013-01-01

    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...

  4. Effect of gender on recovery after spinal cord injury.

    Science.gov (United States)

    Chan, Wai-Man; Mohammed, Yahya; Lee, Isabel; Pearse, Damien D

    2013-08-01

    Spinal cord injury (SCI) is a debilitating condition that affects thousands of new individuals each year, the majority of which are males. Males with SCI tend to be injured at an earlier age, mostly during sports or motor vehicle accidents, whereas females tend be injured later in life, particularly in the age group 65 and older. In both experimental and clinical studies, the question as to whether gender affects outcome has been addressed in a variety of patient groups and animal models. Results from experimental paradigms have suggested that a gender bias in outcome exists that favors females and appears to involve the advantageous or disadvantageous effects of the gonadal sex hormones estrogen and progesterone or testosterone, respectively. However, other studies have shown an absence of gender differences in outcome in specific SCI models and work has also questioned the involvement of female sex hormones in the observed outcome improvements in females. Similar controversy exists clinically, in studies that have examined gender disparities in outcome after SCI. The current review examines the experimental and clinical evidence for a gender bias in outcome following SCI and discusses issues that have made it difficult to conclusively answer this question.

  5. INTRATHECAL MIDAZOLAM PROLONGS THE ANALGESIC EFFECTS OF SPINAL BLOCKADE WITH LIDOCAINE FOR PERINEAL OPERATION

    Directory of Open Access Journals (Sweden)

    B. Jahangiri R. Jahangiri

    2006-09-01

    Full Text Available Intrathecal administration of midazolam has been reported to have antinociceptive action, and to be an effective analgesic agent. In this prospective double-blind study we aimed to evaluate the postoperative effects of intrathecal midazolam with lidocaine following perineal operation. Forty patients were randomly allocated to two groups: 20 patients in the control group received 2 ml of 5% heavy lidocaine plus 0.4 ml of 0.9% saline intrathecally; 20 patients in the midazolam group received 2 ml of 5% heavy lidocaine plus 0.4 ml of 0.5% midazolam. Duration of analgesia was significantly greater in the midazolam group (7  1 hours compared to the control group (1.5  0.5 hours.

  6. The effect of intravenous morphine on the level of spinal anesthesia with lidocaine.

    Science.gov (United States)

    Masoudifar, Mehrdad; Aghadavoudi, Omid; Rezvani, Mehran; Mashayekhi, Neda

    2012-01-01

    One of the major concerns in spinal anesthesia with lidocaine is its short duration of action. Enhancement is necessary in some situations during surgery, because surgeons encounter with unexpected events and need more time. Therefore there is a need to increase anesthesia duration in these situations. Many studies investigated various additives with different administration routes to enhance spread and duration of spinal block with lidocaine. Because we only have morphine sulfate in our clinics and the sulfate compounds are neurotoxic, we cannot prescribe it by intrathecal route; for this reason we investigated effects of intravenous morphine on the spinal anesthesia with lidocaine. This double blinded randomized clinical trial study was performed on 36 patients who were allocated to two groups. All patients underwent spinal anesthesia with lidocaine by the same method. Patients in the case group received morphine plus midazolam intravenously as the additive medication and in the control group received normal saline plus midazolam. Duration, spinal block level, recovery time, sedation score and adverse effects were compared between the two groups. This study showed that although intravenous morphine can provide better safe sedation (p-value < 0.01), it has no effect on the level (p-value: 0.42) and duration of spinal block (p-value: 0.26). Although heart rate and blood pressure had significant decrease in the case group (p-value < 0.01 and < 0.05 respectively) but the need for administration of ephedrine was completely similar in both groups. Although some studies had proved the efficacy of systemic use of other opioids including fentanyl and sufentanil, morphine had no effect on the level and duration of spinal block. It can be due to differences in the chemical structures of these substances. However, intravenous morphine as an additive to spinal anesthesia with lidocaine can provide acceptable sedation with no major side effects.

  7. The effect of spinal manipulation on deep experimental muscle pain in healthy volunteers

    DEFF Research Database (Denmark)

    O'Neill, Søren; Ødegaard-Olsen, Øystein; Søvde, Beate

    2015-01-01

    BACKGROUND: High-velocity low-amplitude (HVLA) spinal manipulation is commonly used in the treatment of spinal pain syndromes. The mechanisms by which HVLA-manipulation might reduce spinal pain are not well understood, but often assumed to relate to the reduction of biomechanical dysfunction....... It is also possible however, that HVLA-manipulation involves a segmental or generalized inhibitory effect on nociception, irrespective of biomechanical function. In the current study it was investigated whether a local analgesic effect of HVLA-manipulation on deep muscle pain could be detected, in healthy...... individuals. METHODS AND MATERIALS: Local, para-spinal muscle pain was induced by injection of 0.5 ml sterile, hyper-tonic saline on two separate occasions 1 week apart. Immediately following the injection, treatment was administered as either a) HVLA-manipulation or b) placebo treatment, in a randomized...

  8. Effects of strontium ranelate on spinal osteoarthritis progression

    DEFF Research Database (Denmark)

    Bruyere, O; Delferriere, D; Roux, C

    2008-01-01

    OBJECTIVE: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment...... years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. RESULTS: The proportion of patients with worsening overall spinal OA score was reduced by 42% in the strontium ranelate group, compared with placebo (RR, 0.58; 95% CI, 0.42 to 0.......79; p = 0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (p = 0.03), while no significant difference was observed in terms of health-related quality of life between these patient groups. CONCLUSIONS...

  9. Anti-nociceptive and anti-inflammatory activities of Wrightia arborea.

    Science.gov (United States)

    Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Mosaddik, Md Ashik

    2013-05-15

    Anti-nociceptive and anti-inflammatory effects of methanolic extract of Wrightia arborea (MEWA) were examined using different models in rats. MEWA was given to rats orally upto 2000 mg kg(-1) b.wt. for acute toxicity study and observed for 14 days. Anti-nociceptive activity was evaluated in rats against Acetic acid induced writhing (chemically induced pain) and Tail immersion method (thermally induced pain). Acute anti-inflammatory activity of MEWA was also evaluated in Formaline-induced rat paw edema model and Carrageenan-induced hind paw edema model in rats. Results demonstrated that no mortality was found upto single dose of 2000 mg kg(-1) b.wt. in rats even after 14 days observation. In comparison to control group MEWA at 100 and 200 mg kg(-1) b.wt. showed highly significant anti-nociceptive activity against chemically (p mechanism.

  10. Antinociceptive Activity of the Chloroform Fraction of Dioclea virgata (Rich. Amshoff (Fabaceae in Mice

    Directory of Open Access Journals (Sweden)

    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.

  11. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

    Directory of Open Access Journals (Sweden)

    A. Schiaveto-de-Souza

    2013-12-01

    Full Text Available Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.

  12. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Schiaveto-de-Souza, A. [Departamento de Morfofisiologia, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS (Brazil); Silva, C.A. da [Departamento de Morfologia,Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Orthopedia e Traumatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bel, E.A.Del [Departamento de Morfologia,Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-04-12

    Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.

  13. Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

    Science.gov (United States)

    Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

    2010-12-01

    The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

  14. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Yunus Nazli

    2015-01-01

    Full Text Available OBJECTIVES: Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model. METHOD: Thirty-two rabbits were divided into the following four equally sized groups: group I (control, group II (ischemia-reperfusion, group III (atorvastatin treatment and group IV (atorvastatin withdrawal. Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses. RESULTS: All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II. CONCLUSION: This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model.

  15. Purification and characterization of a novel antinociceptive toxin from Cobra venom (Naja naja atra).

    Science.gov (United States)

    Jiang, Wei-jian; Liang, Ying-xia; Han, Li-ping; Qiu, Peng-xin; Yuan, Jin; Zhao, Shu-jin

    2008-10-01

    Snake venoms have demonstrated antinociceptive activity, and certain isolated neurotoxins have demonstrated significant analgesia in animal models. Here we report a novel analgesic toxin which was isolated from Naja naja atra and was given the name 'najanalgesin'. The LD(50) of the crude venom and najanalgesin were 0.89mg/kg and 2.69mg/kg, respectively. We used the writhing test and hot plate test to evaluate the antinociceptive properties of the crude venom and najanalgesin after intraperitoneal (ip) administration. The analgesic mechanism of najanalgesin was also studied. The response latency time was significantly prolonged in the hot plate test after ip administration of the crude venom of Naja naja atra (0.111-0.445mg/kg) in a dose-dependent manner. Najanalgesin (1mg/kg) elicited almost the same antinociceptive effect as that of the crude venom of Naja naja atra at the dose of 0.445mg/kg and remained for 6h after intraperitoneal injection, shown by hot plate test. The percentage of increase in the latency time for the venom and the najanalgesin 3h after drug administration was 96.2% and 112%, respectively. The number of writhes decreased to almost 1/3, 1/6, and 1/12 of the NS (physiological saline) group after intraperitoneal administration of najanalgesin at 0.25, 0.5, and 1.0mg/kg, respectively. Pretreatment with atropine (1mg/kg) or naloxone (3mg/kg) blocked the antinociception of najanalgesin in the hot plate test. Based on the sequence information, najanalgesin is found to be highly homologous with the conventional CTXs (cardiotoxins). To our knowledge, no study had previously reported that a toxin which was homologous with CTXs possessed the antinociceptive activity. Thus, this is the first report that the antinociceptive effect induced by najanalgesin is mediated by cholinergic and opioidergic mechanisms.

  16. Effect of sildenafil on erectile dysfunction in spinal Cord injured ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction is a preoccupying issue, just like motor and bladder disability, in spinal cord injured (SCI) patients. This is particularly so because of the increasing prevalence of paraplegic and tetraplegic subjects and the fact that these patients are younger, and sexually active. Objective: To determine the ...

  17. Activity-Guided Isolation of Bioactive Constituents with Antinociceptive Activity from Muntingia calabura L. Leaves Using the Formalin Test

    Directory of Open Access Journals (Sweden)

    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.

  18. Activity-Guided Isolation of Bioactive Constituents with Antinociceptive Activity from Muntingia calabura L. Leaves Using the Formalin Test.

    Science.gov (United States)

    Mohamad Yusof, Mohd Izwan; Salleh, Mohd Zaki; Lay Kek, Teh; Ahmat, Norizan; Nik Azmin, Nik Fatini; Zakaria, Zainul Amiruddin

    2013-01-01

    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.

  19. Neuroprotective effect of allicin in a rat model of acute spinal cord injury.

    Science.gov (United States)

    Lv, Runxiao; Mao, Ningfang; Wu, Jinhui; Lu, Chunwen; Ding, Muchen; Gu, Xiaochuan; Wu, Yungang; Shi, Zhicai

    2015-12-15

    This study aims to investigate the effect of allicin on motor functions and histopathologic changes after spinal cord injury and the mechanism underlying its neuroprotective effects. The motor function of rats was evaluated with the Basso, Beattie, and Bresna test. Histopathologic changes were evaluated by hematoxylin and eosin and Nissl staining. Spinal cord oxidative stress markers were determined by measuring glutathione and malondialdehyde content and superoxide dismutase activity using commercial kits. Inflammatory factors were determined by measuring tumor necrosis factor-α, interleukin-1β and interleukin-6 using ELISA assay. Apoptosis was examined using TUNEL staining. The effect of allicin on Nrf2 protein levels and localization was assessed using immunofluorescence staining and Western blotting analysis. Results demonstrated that allicin accelerated the motor functional recovery and protected neuron damage against spinal cord injury (SCI). SCI-induced oxidative stress, inflammatory response and cell apoptosis in the spinal cord were also prevented by allicin. In addition, we observed that SCI increased Nrf2 nuclear expression, and allicin treatment further increased Nrf2 nuclear translocation in neurons and astrocytes. siRNA-mediated Nrf2 gene knockdown completely blocked the effect of allicin on spinal cord tissue. Our finding suggests that allicin promotes the recovery of motor function after SCI in rats, and this effect may be related to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Allicin mediated Nrf2 nuclear translocation may be involved in the protective effect as well. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats.

    Science.gov (United States)

    Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin

    2016-05-01

    [Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin

  1. Systematic administration of B vitamins attenuates neuropathic hyperalgesia and reduces spinal neuron injury following temporary spinal cord ischaemia in rats.

    Science.gov (United States)

    Yu, C-Z; Liu, Y-P; Liu, S; Yan, M; Hu, S-J; Song, X-J

    2014-01-01

    B vitamins have been demonstrated to be effective in treating chronic pain due to peripheral nerve injury. We investigated whether B vitamins could alleviate neuropathic pain and reduce neuron injury following temporary ischaemia in a rat model of spinal cord ischaemia-reperfusion injury (SCII). SCII was produced by transiently blocking the unilateral lumbar arteries in adult male Sprague-Dawley rats. Behavioural and neurochemical signs of neuropathic pain and spinal neuron injury were analysed with and without B vitamin treatment. SCII caused behavioural thermal hyperalgesia and mechanical allodynia and neurochemical alterations, including increased expression of the vanilloid receptor 1 (VR1) and induction of c-Fos, as well as activation of the astrocytes and microglial cells in the spinal cord. Repetitive systemic administration of vitamin B complex (B1/B6/B12 at 33/33/0.5 mg/kg, i.p., daily, for 7-14 consecutive days) significantly reduced thermal hyperalgesia and the increased expression of VR1 and c-Fos, as well as activation of the astrocytes and microglial cells. SCII caused a dramatic decrease of the expression of the rate-limiting enzyme glutamic acid decarboxylase-65 (GAD65), which synthesizes γ-aminobutyric acid (GABA) in the axonal terminals, and β-III-tubulin, and also caused loss of Nissl bodies in the spinal cord. These alterations were largely prevented and rescued by the B vitamin treatment. These findings support the idea that the B vitamins are capable of neuroprotection and antinociception during spinal cord injury due to temporary ischaemia. Rescuing the loss of inhibitory GABAergic tone may reduce spinal central sensitization and contribute to B vitamin-induced analgesia. © 2013 European Pain Federation - EFIC®

  2. Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

    Science.gov (United States)

    Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

    2015-11-01

    Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    da Matta, Carolina Babosa Brito; de Souza, Éverton Tenório; de Queiroz, Aline Cavalcanti; de Lira, Daysianne Pereira; de Araújo, Morgana Vital; Cavalcante-Silva, Luiz Henrique Agra; de Miranda, George Emmanuel C.; de Araújo-Júnior, João Xavier; Barbosa-Filho, José Maria; de Oliveira Santos, Bárbara Viviana; Alexandre-Moreira, Magna Suzana

    2011-01-01

    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(s) responsible for the

  5. Effects of spinal cord stimulation on motor functions in children with cerebral palsy.

    Science.gov (United States)

    Solopova, I A; Sukhotina, I A; Zhvansky, D S; Ikoeva, G A; Vissarionov, S V; Baindurashvili, A G; Edgerton, V R; Gerasimenko, Y P; Moshonkina, T R

    2017-02-03

    Is it possible to regulate the functional properties of abnormally developed spinal neuronal locomotor networks using transcutaneous spinal cord stimulation? This question has been studied in twenty-eight participants (∼9 yrs) with spastic cerebral palsy, and mainly Gross Motor Function Classification System for Cerebral Palsy level III. The participants were randomly assigned to two groups. The experimental group received transcutaneous spinal cord stimulation at two spinal levels (over T11 and L1 spinous processes), combined with locomotor treadmill training, whereas the participants of the control group received locomotor treadmill training only. After spinal cord stimulation in the experimental group we found an incremental increase in knee torque whereas in the control group this effect was absent. The amplitude of hip motion increased in both groups. A decrease of co-activation of hip and muscles of the lower extremities was observed in the experimental group while in the control group co-activation decreased only in hip muscles. The results support the idea that locomotor function can be improved significantly with the combination of training and transcutaneous spinal cord stimulation than with training alone. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism

    Directory of Open Access Journals (Sweden)

    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.

  7. Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

    Science.gov (United States)

    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).

  8. Anti-inflammatory and anti-nociceptive effect of Betula platyphylla var. japonica in human interleukin-1β-stimulated fibroblast-like synoviocytes and in experimental animal models.

    Science.gov (United States)

    Huh, Jeong-Eun; Hong, Jang-Mu; Baek, Yong-Hyeon; Lee, Jae-Dong; Choi, Do-Young; Park, Dong-Suk

    2011-04-26

    Traditional medicine has widely been used Betula platyphylla var. japonica to treat various inflammatory diseases including arthritis. To determine the anti-inflammatory, anti-nociceptive, and anti-arthritic effects of Betula platyphylla in interleukin-1β (IL-1β)-stimulated fibroblast-like synoviocytes from human rheumatoid arthritis and in nociceptive and inflammatory animal model. The inflammatory mediators such as IL-6, tumor necrosis factor (TNF)-α matrix metalloproteinase (MMP)-1, MMP-13, inducible nitric oxide synthesis (iNOS), nitrites, prostaglandin E(2) (PGE(2)) and cyclo-oxygenase 2 (COX-2) activity of Betula platyphylla were tested in IL-1β-stimulated fibroblast-like synoviocytes. Tail withdrawal in response to thermal stimulation in tail flick test or paw flinching and shaking in response to sc hind paw formalin injection was measured 1h after oral administration of Betula platyphylla. The former was evaluated with a paw pressure test, and the latter was measured using the squeaking score, and paw volume in inflammatory arthritis tests. Betula platyphylla significantly inhibited proliferation of IL-1β-induced synoviocytes. Betula platyphylla reduced the levels of inflammatory mediators, such as IL-6, TNF-α, MMP-1, MMP13, and PGE(2). In particular, Betula platyphylla significantly inhibited the releases of nitrites and iNOS, as well as release of NFκB, into the nucleus of IL-1β-treated synoviocytes, even at concentrations as low as 1μg/ml. Oral administrant of Betula platyphylla at 400mg/kg significantly decreased about 27.8% of tail flick withdrawal and inhibited about the number of paw flinches in both phases 1 and 2 of the formalin test. In the carrageenan-induced acute pain and arthritis model, Betula platyphylla dose dependently reduced the nociceptive threshold and the arthritic symptoms at day 8, respectively, and Betula platyphylla at 400mg/kg markedly reduced the inflammatory area about 48% in the ankle joints. This capacity of Betula

  9. Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid.

    Science.gov (United States)

    Shang, Ai-Jia; Yang, Ying; Wang, Hang-Yan; Tao, Ben-Zhang; Wang, Jing; Wang, Zhong-Feng; Zhou, Ding-Biao

    2017-04-01

    Pathophysiology of spinal cord injury (SCI) causes primary and secondary effects leading to loss of neuronal function. The aim of the present study was to investigate the role of rosmarinic acid (RA) in protection against SCI. The experimental study was carried out in male wistar rats categorized into three groups. Group I - sham operated rats; Group II - SCI; Group III - SCI followed by RA treatment (10 mg/kg). The spinal tissues after treatment schedule were analyzed for oxidative stress status through determination of reactive oxygen species (ROS), lipid peroxidation, protein damage (carbonyl and sulfhydryl contents), and antioxidant enzyme activities. The expression of oxidative stress factors NF-κB and Nrf-2 was determined by Western blot analysis. Further pro-inflammatory cytokines (TNF-α, IL-6, MCP-1, and IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The results show that treatment with RA significantly enhances the antioxidant status and decrease the oxidative stress in wistar rats post-SCI. RA effectively ameliorated inflammatory mechanisms by downregulation of NF-κB and pro-inflammatory cytokines post-SCI. The study demonstrates for the first time on the role of RA in protecting the spinal cord from injury and demonstrates its neuroprotection in wistar rats.

  10. The Effects of rhBMP-2 Used for Spinal Fusion on Spinal Cord Pathology After Traumatic Injury

    Science.gov (United States)

    2009-07-29

    that can accommodate stretching and deformation experienced during spinal movement and postural changes. These properties of the outermost dura are...anterior cervical spine fusion. Spine 31:542-547. Sjolund BH (2002) Pain and rehabilitation after spinal cord injury: the case of sensory spasticity ...Spine 28:134-139. Sjolund BH (2002) Pain and rehabilitation after spinal cord injury: the case of sensory spasticity ? Brain Res Brain Res Rev 40

  11. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy

    NARCIS (Netherlands)

    de Vos, C.; de Vos, Cecile C.; Rajan, Vinayakrishnan; Steenbergen, Wiendelt; van der Aa, Hans E.; Buschman, H.P.J.

    2009-01-01

    Aim: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect

  12. Objective methods for the assessment of the spinal and supraspinal effects of opioids

    DEFF Research Database (Denmark)

    Fischer, Iben W; Hansen, Tine M; Lelic, Dina

    2017-01-01

    into the blood, where receptor distribution, density and activity in the brain can be visualized. Spontaneous EEG is typically quantified in frequency bands, power spectrum and spectral edge frequency. EPs are brain responses (assessed by EEG) to a predefined number of short phasic stimuli. EPs are quantified...... by their peak latencies and amplitudes, power spectrum, scalp topographies and brain source localization. For assessment of opioid effects at the spinal level, the following methods are evaluated: the nociceptive withdrawal reflex (NWR) and spinal EPs. The nociceptive withdrawal reflex can be recorded from all...... for assessment of opioid effects may increase knowledge on the CNS processes responsible for analgesia. The aim of this review was to provide an overview of the most common objective methods for assessment of the spinal and supraspinal effects of opioids and discuss their advantages and limitations. METHOD...

  13. The anti-inflammatory and anti-nociceptive activities of Patrinia ...

    African Journals Online (AJOL)

    This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX ...

  14. Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

    Science.gov (United States)

    Beltrán-Villalobos, Karla Lyzet; Déciga-Campos, Myrna; Aguilar-Mariscal, Hidemi; González-Trujano, María Eva; Martínez-Salazar, María Fernanda; Ramírez-Cisneros, María de Los Ángeles; Rios, María Yolanda; López-Muñoz, Francisco Javier

    2017-10-01

    Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Zexp) was lower than the theoretical value (Zadd). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Enhancement of antinociception but not constipation by combinations containing tramadol and metamizole in arthritic rats.

    Science.gov (United States)

    López-Muñoz, Francisco Javier; Moreno-Rocha, Luis Alfonso; Bravo, Guadalupe; Guevara-López, Uriah; Domínguez-Ramírez, Adriana Miriam; Déciga-Campos, Myrna

    2013-10-01

    The use of a combination of analgesics could provide an optimal pain treatment with minimal side effects. Combinations of tramadol and some nonsteroidal anti-inflammatory drugs have demonstrated synergistic antinociceptive effects as well as a significantly reduced occurrence of adverse effects. The purpose of this study was to investigate the antinociceptive and constipation effects of tramadol and metamizole alone or in combination in rats and to discern among the types of drug interactions that exist using dose-response curves and an isobolographic analysis. The antinociceptive effects of tramadol and metamizole, alone or in various combination ratios, were quantitatively evaluated using the "pain-induced functional impairment model in the rat." Additionally, the constipation effect was evaluated using the charcoal meal test. Tramadol (3.2-56.2 mg/kg) and metamizole (56.2-562.3 mg/kg) demonstrated a dose-dependent response with tramadol being more efficacious and potent than metamizole. Twenty-five different combinations of tramadol with metamizole were analyzed, and the evaluated combinations exhibited antinociceptive effects that were either additive or potentiative. An optimal combination was established with 3.2 mg/kg of tramadol and 316.2 mg/kg of metamizole. However, the constipation observed with this combination was more severe than that observed with the administration of tramadol alone. Our results reveal a possible interaction between the two drugs, which may be pharmacokinetic and/or pharmacodynamic in nature. The preclinical antinociceptive interaction and adverse effects produced by the combination of tramadol and metamizole suggests that caution should be exercised when using this combination in the clinical therapy of pain. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  16. Antinociceptive properties of shikonin: in vitro and in vivo studies.

    Science.gov (United States)

    Gupta, Bhawana; Chakraborty, Sabyasachi; Saha, Soumya; Chandel, Sunita Gulabsingh; Baranwal, Atul Kumar; Banerjee, Manish; Chatterjee, Mousumi; Chaudhury, Ashok

    2016-07-01

    Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

  17. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

    Directory of Open Access Journals (Sweden)

    Bingbing Liu

    2015-01-01

    Full Text Available Ulinastatin (UTI, a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.

  18. Effects of paired transcutaneous electrical stimulation delivered at single and dual sites over lumbosacral spinal cord.

    Science.gov (United States)

    Sayenko, Dimitry G; Atkinson, Darryn A; Floyd, Terrance C; Gorodnichev, Ruslan M; Moshonkina, Tatiana R; Harkema, Susan J; Edgerton, V Reggie; Gerasimenko, Yury P

    2015-11-16

    It was demonstrated previously that transcutaneous electrical stimulation of multiple sites over the spinal cord is more effective in inducing robust locomotor behavior as compared to the stimulation of single sites alone in both animal and human models. To explore the effects and mechanisms of interactions during multi-site spinal cord stimulation we delivered transcutaneous electrical stimulation to the single or dual locations over the spinal cord corresponding to approximately L2 and S1 segments. Spinally evoked motor potentials in the leg muscles were investigated using single and paired pulses of 1ms duration with conditioning-test intervals (CTIs) of 5 and 50ms. We observed considerable post-stimulation modulatory effects which depended on CTIs, as well as on whether the paired stimuli were delivered at a single or dual locations, the rostro-caudal relation between the conditioning and test stimuli, and on the muscle studied. At CTI-5, the paired stimulation delivered at single locations (L2 or S1) provided strong inhibitory effects, evidenced by the attenuation of the compound responses as compared with responses from either single site. In contrast, during L2-S1 paradigm, the compound responses were potentiated. At CTI-50, the magnitude of inhibition did not differ among paired stimulation paradigms. Our results suggest that electrical stimuli delivered to dual sites over the lumbosacral enlargement in rostral-to-caudal order, may recruit different populations of motor neurons initially through projecting sensory and intraspinal connections and then directly, resulting in potentiation of the compound spinally evoked motor potentials. The interactive and synergistic effects indicate multi-segmental convergence of descending and ascending influences on the neuronal circuitries during electrical spinal cord stimulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain.

    Science.gov (United States)

    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).

  20. Modulation by insulin rather than blood glucose of the pain threshold in acute physiological and flavone induced antinociception in mice.

    Science.gov (United States)

    Rajendran, N N; Thirugnanasambandam, P; Parvathavarthini, S; Viswanathan, S; Ramaswamy, S

    2001-10-01

    The present study investigated the cause effect relationship between glycemic and algesic states. The hypo- and hyperglycemic conditions were induced physiologically through exercise (3 min swim at room temperature 28 degrees - 30 degrees C) and external dextrose (2 g/kg, ip) administration respectively in mice. Besides, flavone (50 mg/kg, sc) a known antinociceptive drug was chosen to study such a cause effect relationship. The anti-nociception was assessed by acetic acid assay, blood glucose measured using glucometer (Ames) and serum insulin by radioimmunoassay. The findings revealed that irrespective of the glycemic state whether hypo-, hyper, or euglycemic induced by swim stress, dextrose or flavone per se respectively, significant antinociceptive response was recorded. Pretreatment with flavone (50 mg/kg, sc) always exhibited a tendency to reverse the hyperglycemia, if any, but enhanced the antinociceptive response either after swim stress or after dextrose. These data support the contention that changes in the glycemic state in acute condition is not responsible for antinociceptive response and thereby suggesting dissociation between these two parameters. Extended studies estimating serum insulin level after the above mentioned maneuvers showed a significant rise whenever antinociceptive response was recorded irrespective of the glycemic state. It is suggested that serum insulin level, a hormonal parameter rather than the blood glucose level, which is a metabolic parameter, appears more reliable. It appears that the changes in serum insulin level produced by various treatments may have a relationship with the antinociceptive response. However, this study has the limitation that the results can apply only for acute conditions and extrapolation to clinical conditions is debatable.

  1. Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain.

    Science.gov (United States)

    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.

  2. Anti-inflammatory and antinociceptive activities of the ethanolic extract of Bougainvillea xbuttiana.

    Science.gov (United States)

    Alvarez Perez Gil, A L; Barbosa Navarro, L; Patipo Vera, M; Petricevich, V L

    2012-12-18

    Bougainvillea xbuttiana is widely distributed in Mexico and it is used as an analgesic in folk medicine. In the present study the in vivo antinociceptive and anti-inflammatory effects of the Bougainvillea xbuttiana ethanolic extract have been studied in mice. The phytochemical analysis was performed. Antinociceptive activity was evaluated through writhing and formalin test in mice. The anti-inflammatory activity was determined with the carrageenan-induced mice paw oedema model. IL-6, IL-10 and IFN-γ levels were determined by enzyme-like immunosorbent assay, whereas TNF and nitrite levels were detected by standard assay with L929 cells and colorimetric Griess reactive, respectively. The results showed that the ethanolic extract of the Bougainvillea xbuttiana has significant anti-inflammatory and antinociceptive activities, by inhibition of nociception induced by acetic acid and paw oedema. This extract also induced a decrease in TNF levels and an increase of IL-6, IFN-γ and NO levels that we observed up to 2h. The highest levels of IL-10 were observed up to 4h. The ratios of pro-/anti-inflammatory cytokines in sera from mice injected with the ethanolic extract, may be manifesting an anti-inflammatory status. The present study provides convincing evidences that Bougainvillea xbuttiana extract possesses significant anti-nociceptive and anti-inflammatory effects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Antinociceptive properties of extracts and two flavonoids isolated from leaves of Danae racemosa.

    Science.gov (United States)

    Maleki-Dizaji, Nasrin; Fathiazad, Fatemeh; Garjani, Alireza

    2007-12-01

    The antinociceptive properties of the hydro-methanolic extract (HME) and two flavonoids isolated from Danae racemosa have been investigated in several nociceptive rat models. The HME from D. racemosa (100-400 mgkg(-1), i.p.) produced significant dose-related inhibition of acetic acid-induced abdominal constriction. In the same dose range, the HME produced dose-related inhibition in both phases of a formalin-test. Treatment of animals with naloxone (5 mgkg(-1), i.p.) completely reversed the antinociceptive effect caused by morphine (5 mgkg(-1), s.c.) and the HME (200 mgkg(-1), i.p.) when assessed against the first phase of the formalin-test, but this effect was less significant for the HME in the second phase. Furthermore, when assessed via a hot-plate test, the HME (100-400 mgkg(-1), i.p.) caused a significant increase in response latency. The HME, given daily for to 7 consecutive days, develop tolerance, but did not induce cross-tolerance to morphine. These data demonstrate that the HME elicites pronounced antinociception against several pain models. The actions of the HME involve, at least in part, an interaction with the opioid system, but does not seem to be related with non-specific peripheral or central depressant actions. Finally, the active principle(s) responsible for the antinociceptive action of D. racemosa is likely to be partially related to the presence of quercetin and kaempferol.

  4. Antinociceptive activity of methanol extract of fruits of Capparis ovata in mice.

    Science.gov (United States)

    Arslan, Rana; Bektas, Nurcan; Ozturk, Yusuf

    2010-08-19

    Capparis ovata Desf. and Capparis spinosa L. have wide natural distribution in Turkey and they are consumed in pickled form. Flower buds, root bark, and fruits of the plant are used in folk medicine due to their analgesic, wound healing, cell regeneration, tonic, and diuretic effects. In this study, we attempted to identify the possible antinociceptive action of methanol extract prepared from fruits of Capparis ovata. Using tail immersion, hot plate and writhing tests, the antinociceptive effect of the methanol extract of Capparis ovata (MEC) fruits was assessed after intraperitoneal administration into mice. Morphine sulfate (5mg/kg; i.p.) and diclofenac (10mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5mg/kg; i.p.) was also tested. MEC was studied at the doses of 50, 100, and 200mg/kg (i.p.) and exhibited significant antinociceptive activities in all tests used. The above-mentioned doses of the extract reduced the writhing responses by 32.21, 55.70, and 68.36%, respectively. MPE% were increased by 7.27, 12.07, 14.60% in the tail immersion, and 7.88, 11.71, 16.73% in the hot plate test at the tested doses, respectively. Naloxone antagonized antinociceptive effect at the doses of 100 and 200mg/kg whereas partially antagonized the effect of MEC at the dose of 50mg/kg. Based on the results obtained, it can be concluded that MEC has antinociceptive effects both at the peripheral and central levels. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  5. [Clinical effects of microsurgery in spinal cord anaplastic astrocytoma].

    Science.gov (United States)

    Zhang, L; Jia, W Q; Kong, D S; Zhang, Z F; Yang, J

    2017-06-01

    Objective: To investigate the surgical outcomes and prognosis of spinal cord anaplastic astrocytoma (AA). Methods: A total of 27 consecutive patients diagnosed as spinal cord AA between January 2008 and May 2015 in Department of Neurosurgery of Beijing Tiantan Hospital were retrospectively reviewed. There were 18 males and 9 females, the mean age was (30.7±13.0) years (ranging from 5 to 52 years). The lesions were located at cervical level in 8 patients, at thoracic level in 9 patients, at cervicothoracic level in 3 patients, and at thoracolumbar level in 7 patients, the average number of vertebral was 3.3±1.3.The median time from onset of symptom to surgery was 4 months, ranging from 3 days to 48 months. The clinical presentations were weakness (23 cases), paresthesia (22 cases), pain (20 cases), sphincter disorder (15 cases) and paralysis (7 cases). The preoperative modified McCormick scale was as follows: grade Ⅱ for 6 cases, grade Ⅲ for 7 cases, grade Ⅳ for 7 cases, grade Ⅴ for 7 cases. The tumors were surgically removed via posterior median approach with the monitoring of the somatosensory-evoked potentials to minimize the neurological injury. All of the patients were recommonded to receive adjuvant chemotherapy and radiotherapy postoperatively after pothological verified and followed up by clinic interview or telephone postoperatively. Log-rank test was used to calculate the survival rate. Results: Gross total resection and subtotal resection were achieved in 18 patients and partial resection in 9. Twenty patients received adjuvant chemotherapy and (or) radiotherapy, 7 patients did not received chemoradiation postoperatively. Nineteen patients died and 8 were alive at the last follow-up. The median survival time was 23 months with 1 and 2-year survival rates of 85.2% and 50.0%.There was no statistical significance between subtotal resection group and partial resection group(χ(2)=0.089, P=0.880), the survival rates of patients in chemotherapy group

  6. The effects of unilateral and bilateral spinal anaesthesia on hemodynamic parameters in patients surgically treated for inguinal hernia: Hemodynamic parameters and spinal anesthesia

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    Milosavljević Snežana

    2016-01-01

    Full Text Available Introduction: Conventional bilateral spinal anaesthesia is commonly used for surgical treatment of inguinal hernia because it causes fast development of block with relatively small dosage of local anaesthetic; furthermore, it is easily administered, reduces the level of metabolic response to stress, reduces the incidence of deep venous thrombosis and respiratory depression. On the other hand, the main side effect is hypotension Objective: The goal of the research was to determine which of the two methods of spinal anaesthesia (conventional bilateral, achieved with regular dosage of long-lasting bupivacaine or hypobaric unilateral, achieved with combined application of bupivacaine and fentanyl ensures higher hemodynamic stability during tension-free hernioplasty in patients from group I and II of ASA classification system. Methods: The research was conducted as a prospective, controlled clinical study with the total amount of 50 patients, males and females, and within the age span ranging from 17 to 77, who all had indications for surgical treatment of one-sided inguinal hernia under spinal anaesthesia. The hemodynamic parameters (heart rate, systolic, diastolic and mean arterial pressure were measured during following intervals: T1 - during preanaesthetic visit, T2 - after premedication and the iv administration of Ringer's lactate solution, T3 - 15 minutes after the administration of spinal anaesthesia, T4 - after the surgical incision, T5 - intraoperatively, T6 - during the placement of the last surgical stitch on the skin, T7 - one hour postoperatively. Results: The results showed that the frequency of clinically relevant hypotension was statistically much higher in patients with bilateral spinal anaesthesia (24 % when compared to patients administered with unilateral spinal anaesthesia (4%. Ten minutes after the application of spinal anaesthesia the mean arterial pressure has decreased by 20% when compared to basic values in group BB, and by

  7. Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

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    Enomoto M

    2016-03-01

    Full Text Available Mitsuhiro Enomoto1,21Department of Orthopaedic and Spinal Surgery, Graduate School, 2Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, JapanAbstract: Neurotrophic factors (NFs play important roles in regenerative medicine approaches to mitigate primary and secondary damage after spinal cord injury (SCI because their receptors are still present in the injured spinal cord even though the expression of the NFs themselves is decreased. Several reports have shown that NF administration increases regenerative signaling after SCI, particularly by stimulating axonal growth. However, few NFs cross the blood–brain barrier, and most of them show low stability and limited diffusion within the central nervous system. To overcome this problem, transplantation strategies using genetically modified NF-secreting Schwann cells, neural and glial progenitor cells, and mesenchymal stem cells have been applied to animal models of SCI. In particular, multifunctional NFs that bind to TrkB, TrkC, and p75NTR receptors have been discovered in the last decade and utilized in preclinical cell therapies for spinal cord repair. To achieve functional recovery after SCI, it is important to consider the different effects of each NF on axonal regeneration, and strategies should be established to specifically harness the multifunctional properties of NFs. This review provides an overview of multifunctional NFs combined with cell therapy in experimental SCI models and a proposal to implement their use as a clinically viable therapy.Keywords: spinal cord injury, neurotrophic factor, multineurotrophin, regeneration, cell transplantation

  8. TRPV1 in Brain Is Involved in Acetaminophen-Induced Antinociception

    Science.gov (United States)

    Eschalier, Alain; Zygmunt, Peter M.; Högestätt, Edward D.

    2010-01-01

    Background 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 (TRPV1) in vitro. Pharmacological activation of TRPV1 in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV1 in the brain contributes to the analgesic effect of acetaminophen. Methodology/Principal Findings Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E2 (PGE2) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV1 in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test. Conclusions This study shows that TRPV1 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 TRPV1 in the brain. PMID:20862299

  9. Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

    Science.gov (United States)

    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

  10. TRPV1 in brain is involved in acetaminophen-induced antinociception.

    Directory of Open Access Journals (Sweden)

    Christophe Mallet

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  11. Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness

    DEFF Research Database (Denmark)

    Randsøe, Thomas; Meehan, Claire Francesca; Broholm, Helle

    2015-01-01

    Nitric oxide (NO) releasing agents have, in experimental settings, been shown to decrease intravascular nitrogen bubble formation and to increase the survival rate during decompression sickness (DCS) from diving. The effect has been ascribed to a possible removal of preexisting micronuclei...... evaluated by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17 s, and spinal cord conduction was studied by measurements of SEPs. Histological samples of the spinal cord were analyzed for lesions...... GTN (group 6) during the dive, before decompression. In all groups, decompression caused considerable intravascular bubble formation. The ISMN groups showed no difference compared with the control group, whereas the GTN groups showed a tendency toward faster SEP disappearance and shorter survival...

  12. Effectiveness of neural mobilization in patients with spinal radiculopathy: a critical review.

    Science.gov (United States)

    Efstathiou, Michalis A; Stefanakis, Manos; Savva, Christos; Giakas, Giannis

    2015-04-01

    Spinal radiculopathy (SR) is a multifactorial nerve root injury that can result in significant pain, psychological stress and disability. It can occur at any level of the spinal column with the highest percentage in the lumbar spine. Amongst the various interventions that have been suggested, neural mobilization (NM) has been advocated as an effective treatment option. The purpose of this review is to (1) examine pathophysiological aspects of spinal roots and peripheral nerves, (2) analyze the proposed mechanisms of NM as treatment of injured nerve tissues and (3) critically review the existing research evidence for the efficacy of NM in patients with lumbar or cervical radiculopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Peripheral inflammation modifies the effect of intrathecal IL-1beta on spinal PGE2 production mainly through cyclooxygenase-2 activity. A spinal microdialysis study in freely moving rats.

    Science.gov (United States)

    Shi, Lin; Smolders, Ilse; Umbrain, Vincent; Lauwers, Mary Helen; Sarre, Sophie; Michotte, Yvette; Zizi, Martin; Camu, Frederic

    2006-02-01

    Acute inflammation induces upregulation of IL-1beta both at the site of the peripheral inflammation and in the cerebrospinal fluid (CSF). The central increase of IL-1beta mainly contributes to the development of hypersensitivity. However, the spinal mechanisms for the effects of IL-1beta in nociceptive transmission are incompletely understood. It is also unknown whether previous sensitization changes IL-1beta activity. We therefore investigated the dose-effect relationship of intrathecal (i.t.) IL-1beta on spinal PGE(2) production in the absence and presence of peripheral formalin inflammation with spinal microdialysis in freely moving rats. The possible involvement of cyclooxygenase (COX) isoforms in the IL-1beta-mediated spinal PGE(2) production on the background of peripheral formalin inflammation was further evaluated with the selective COX-1 and COX-2 inhibitors. We found that the i.t. administration of IL-1beta, with doses of 1, 2, 8, or 16 ng, increased PGE(2) levels in CSF in a dose-related fashion. This IL-1beta-evoked PGE(2) release occurred within 30min after IL-1beta administration, peaked at 30-60 min interval, and returned gradually to the baseline level within 4h. Peripheral formalin inflammation in the paw induced a more prolonged effect of spinal IL-1beta with larger PGE(2) releases in the CSF compared with the non-inflammatory state, suggesting that peripheral inflammation enhances central sensitization. The COX-2 inhibitor SC58236 (15 mg/kg) reduced the IL-1beta-mediated PGE(2) increase in CSF by 86% while the COX-1 inhibitor SC58560 (15 mg/kg) had less effect (28%). Our study suggests that mainly the COX-2 enzyme mediates the IL-1beta-induced increase in spinal PGE(2) in the presence of peripheral formalin inflammation.

  14. Antinociceptive and anti-inflammatory potentials of kolaviron: mechanisms of action.

    Science.gov (United States)

    Onasanwo, Samuel A; Rotu, Rume A

    2016-06-01

    Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron. The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation. In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron

  15. The Effect of Early Initiation of Rehabilitation after Lumbar Spinal Fusion

    DEFF Research Database (Denmark)

    Oestergaard, Lisa Gregersen; Nielsen, Claus Vinther; Bünger, Cody E

    2012-01-01

    ABSTRACT: Study design: A multicenter RCT including 82 patients.Objective: To examine the effect of early initiation of rehabilitation after instrumented lumbar spinal fusion.Summary of Background Data: Lumbar spinal fusion has been performed for more than 70 years. Yet, only few studies have exa...... work. Wilcoxon rank sum test was used to compare the groups in terms of differences from baseline to 6 months and 1-year follow-up.Results: According to the ODI, at 1-year follow-up, the 6w-group had a median reduction of -6(-19;4) compared with -20(-30;-7) in the 12w-group (p...

  16. The Effects of Epidural Top-Up Technique with Serum Physiological On Unilateral Spinal Anesthesia

    OpenAIRE

    İlkay Cömert; Koray Erbüyün; Gülay Ok; İdil Tekin; Demet Tok

    2006-01-01

    This study was designed to investigate the influence of saline injections as epidural top-up on the sensory block duration, quality and hemodynamic effects of unilateral spinal anesthesia. The cases from ASA I-Il containing of 18-65 age group were randomly separated into three groups. For the purpose of unilateral spinal anesthesia, 6 mg 0.5% ‘heavy’ bupivacaine and for the purpose of epidural top-up, 10 mL saline were applied to the each patients of the groups. The study protocol was desi...

  17. Effects of prophylactic ondansetron on spinal anesthesia-induced hypotension: a meta-analysis.

    Science.gov (United States)

    Gao, L; Zheng, G; Han, J; Wang, Y; Zheng, J

    2015-11-01

    A range of strategies including physical interventions, intravenous fluids and vasopressor drugs have been used to minimize or prevent spinal anesthesia-induced hypotension. Recent studies suggest that ondansetron, a commonly used antiemetic, also affects hypotension. This systematic review investigated the effects of prophylactic ondansetron on hemodynamic changes following spinal anesthesia. Medline, Embase, Cochrane Library databases and www.clinicaltrials.gov were searched for randomized controlled trials studying the effects of ondansetron on hemodynamic changes induced by spinal anesthesia. The primary outcome was hypotension. Relative risk (RR) or mean difference, with 95% confidence intervals (CI), were used to analyze outcomes. Ten randomized controlled trials with 863 patients were included in the analysis. Prophylactic ondansetron reduced the incidence of spinal anesthesia-induced hypotension in both obstetric and non-obstetric patients. The RR of spinal anesthesia-induced hypotension after ondansetron administration was 0.53 (95% CI 0.32 to 0.86) in obstetric patients and 0.16 (95% CI 0.05 to 0.51) in non-obstetric patients. There was significant heterogeneity among obstetric studies (I(2) = 71%). Ondansetron also reduced the incidence of bradycardia, nausea and vomiting after spinal anesthesia with RRs of 0.27 (95% CI 0.16 to 0.47), 0.24 (95% CI 0.14 to 0.42) and 0.48 (95% CI 0.08 to 3.08), respectively. The doses of ephedrine and phenylephrine required to treat hypotension were reduced by ondansetron with mean differences of -2.35 mg (95% CI -4.14 to -0.55 mg) and -31.16 μg (95% CI -57.46 to -4.87 μg), respectively. This review suggests that prophylactic ondansetron reduces the incidence of spinal anesthesia-induced hypotension and vasopressor consumption in both obstetric and non-obstetric patients. In addition, ondansetron can also reduce related adverse outcomes such as bradycardia, nausea and vomiting. However, given the relatively large

  18. 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.

  19. Evaluation of Anti-Nociceptive and Anti-Inflammatory Activities of a Heterofucan from Dictyota menstrualis

    Directory of Open Access Journals (Sweden)

    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.

  20. Evaluation of anti-nociceptive and anti-inflammatory activities of a heterofucan from Dictyota menstrualis.

    Science.gov (United States)

    Albuquerque, Ivan Rui Lopes; Cordeiro, Sara Lima; Gomes, Dayanne Lopes; Dreyfuss, Juliana Luporini; Filgueira, Luciana Guimarães Alves; Leite, Edda Lisboa; Nader, Helena Bonciani; Rocha, Hugo Alexandre Oliveira

    2013-08-02

    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.

  1. Neuroprotective effects of sildenafil in experimental spinal cord injury in rabbits

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    Hasan Kara

    2015-01-01

    Full Text Available Neuroprotective agents such as methylprednisolone and sildenafil may limit damage after spinal cord injury. We evaluated the effects of methylprednisolone and sildenafil on biochemical and histologic changes after spinal cord injury in a rabbit model. Female New Zealand rabbits (32 rabbits were allocated to 4 equal groups: laminectomy only (sham control or laminectomy and spinal trauma with no other treatment (trauma control or treatment with either methylprednisolone or sildenafil. Gelsolin and caspase-3 levels in cerebrospinal fluid and plasma were determined, and spinal cord histology was evaluated at 24 hours after trauma. There were no differences in mean cerebrospinal fluid or plasma levels of caspase-3 between the groups or within the groups from 0 to 24 hours after injury. From 0 to 24 hours after trauma, mean cerebrospinal fluid gelsolin levels significantly increased in the sildenafil group and decreased in the sham control and the trauma control groups. Mean plasma gelsolin level was significantly higher at 8 and 24 hours after trauma in the sildenafil than other groups. Histologic examination indicated that general structural integrity was better in the methylprednisolone in comparison with the trauma control group. General structural integrity, leptomeninges, white and grey matter hematomas, and necrosis were significantly improved in the sildenafil compared with the trauma control group. Caspase-3 levels in the cerebrospinal fluid and blood were not increased but gelsolin levels were decreased after spinal cord injury in trauma control rabbits. Sildenafil caused an increase in gelsolin levels and may be more effective than methylprednisolone at decreasing secondary damage to the spinal cord. 

  2. The Methanolic Extract fromMurraya koenigiiL. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+Channel as Antinociceptive Mechanism.

    Science.gov (United States)

    Sharmin Ani, Nushrat; Chakraborty, Sudip; Moniruzzaman, Md

    2016-01-01

    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 koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine.

  3. The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism

    Science.gov (United States)

    Sharmin Ani, Nushrat; Chakraborty, Sudip

    2016-01-01

    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 koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine. PMID:27812367

  4. Spinal tumor

    Science.gov (United States)

    Tumor - spinal cord ... tissue) Myeloma (blood cancer that starts in the plasma cells of the bone marrow) A small number of spinal tumors occur in the nerves of the spinal cord itself. Tumors that start in spinal tissue are ...

  5. Effects of dynamic sitting interventions on tissue oxygenation in individuals with spinal cord disorders

    NARCIS (Netherlands)

    Reenalda, Jasper; van Geffen, P.; Snoek, G.; Jannink, M.J.A.; IJzerman, Maarten Joost; Rietman, Johan Swanik

    2010-01-01

    Study Design: An explorative cross-sectional study. Objectives: The objective of this study was to investigate the possibility of imposing dynamic sitting behavior on individuals with spinal cord disorders by using the Dynasit chair and to investigate its effect on the (sub-)cutaneous tissue

  6. Effect and process evaluation of implementing standardized tests to monitor patients in spinal cord injury rehabilitation

    NARCIS (Netherlands)

    de Groot, S.; Bevers, G.; Post, M.W.; Woldring, F.A.; Mulder, D.G.; van der Woude, L.H.V.

    2010-01-01

    Purpose. To evaluate the implementation of standardized physical and functional tests to monitor patients with a spinal cord injury (SCI) in eight rehabilitation centers and to analyze the enablers and the barriers of the implementation process. Method. The method involved prospective effect and

  7. The Effect of Spinal Cord Stimulation (SCS) on Static Balance and Gait.

    NARCIS (Netherlands)

    Rijken, N.H.M.; Vonhogen, L.H.; Duysens, J.E.J.; Keijsers, N.L.

    2013-01-01

    Objectives: To investigate whether spinal cord stimulation (SCS) has a negative effect on static balance and gait, which is implicated by the increased incidence of falls leading to frequently occurring lead migrations. Materials and Methods: A controlled trial is performed with 11 subjects (four

  8. Effectiveness of Surgery for Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Machado, G.C.; Ferreira, P.H.; Harris, I.A.; Pinheiro, M.B.; Koes, B.W.; van Tulder, M.; Rzewuska, M.; Maher, C.G.; Ferreira, M.L.

    2015-01-01

    Background: The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of

  9. Effectiveness of surgery for lumbar spinal stenosis : A systematic review and meta-analysis

    NARCIS (Netherlands)

    Machado, G.C. (Gustavo C.); P.H. Ferreira (P.); I. Harris (Ian); Pinheiro, M.B. (Marina B.); B.W. Koes (Bart); M.W. van Tulder (Maurits); Rzewuska, M. (Magdalena); C. Maher (Chris); M.L. Ferreira (Manuela L.)

    2015-01-01

    textabstractBackground: The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the

  10. Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat.

    Science.gov (United States)

    Gautam, M; Prasoon, P; Kumar, R; Reeta, K H; Kaler, S; Ray, S B

    2016-03-01

    Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet. Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated. Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision. In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.

  11. Colokinetic effect of noradrenaline in the spinal defecation center: implication for motility disorders.

    Science.gov (United States)

    Naitou, Kiyotada; Shiina, Takahiko; Kato, Kurumi; Nakamori, Hiroyuki; Sano, Yuuki; Shimizu, Yasutake

    2015-07-28

    Chronic abdominal pain in irritable bowel syndrome (IBS) usually appears in combination with disturbed bowel habits, but the etiological relationship between these symptoms remains unclear. Noradrenaline is a major neurotransmitter controlling pain sensation in the spinal cord. To test the hypothesis that the descending noradrenergic pathway from the brain stem moderates gut motility, we examined effects of intrathecal application of noradrenaline to the spinal defecation center on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anesthetized rats. Intrathecal application of noradrenaline into the L6-S1 spinal cord, where the lumbosacral defecation center is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons by tetrodotoxin blocked the effect of noradrenaline. Pharmacological experiments showed that the effect of noradrenaline is mediated primarily by alpha-1 adrenoceptors. The enhancement of colorectal motility by intrathecal noradrenaline was abolished by severing of the pelvic nerves. Our results demonstrate that noradrenaline acting on sacral parasympathetic preganglionic neurons through alpha-1 adrenoceptors causes propulsive motility of the colorectum in rats. Considering that visceral pain activates the descending inhibitory pathways including noradrenergic neurons, our results provide a rational explanation of the concurrent appearance of chronic abdominal pain and colonic motility disorders in IBS patients.

  12. Effects of Strontium Ranelate on Spinal Interbody Fusion Surgery in an Osteoporotic Rat Model.

    Directory of Open Access Journals (Sweden)

    Tsung-Ting Tsai

    Full Text Available Osteoporosis is a bone disease that afflicts millions of people around the world, and a variety of spinal integrity issues, such as degenerative spinal stenosis and spondylolisthesis, are frequently concomitant with osteoporosis and are sometimes treated with spinal interbody fusion surgery. Previous studies have demonstrated the efficacy of strontium ranelate (SrR treatment of osteoporosis in improving bone strength, promoting bone remodeling, and reducing the risk of fractures, but its effects on interbody fusion surgery have not been adequately investigated. SrR-treated rats subjected to interbody fusion surgery exhibited significantly higher lumbar vertebral bone mineral density after 12 weeks of treatment than rats subjected to the same surgery but not treated with SrR. Furthermore, histological and radiographic assessments showed that a greater amount of newly formed bone tissue was present and that better fusion union occurred in the SrR-treated rats than in the untreated rats. Taken together, these results show significant differences in bone mineral density, PINP level, histological score, SrR content and mechanical testing, which demonstrate a relatively moderate effect of SrR treatment on bone strength and remodeling in the specific context of recovery after an interbody fusion surgery, and suggest the potential of SrR treatment as an effective adjunct to spinal interbody fusion surgery for human patients.

  13. Effects of Strontium Ranelate on Spinal Interbody Fusion Surgery in an Osteoporotic Rat Model.

    Science.gov (United States)

    Tsai, Tsung-Ting; Tai, Ching-Lung; Ho, Natalie Yi-Ju; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer

    2017-01-01

    Osteoporosis is a bone disease that afflicts millions of people around the world, and a variety of spinal integrity issues, such as degenerative spinal stenosis and spondylolisthesis, are frequently concomitant with osteoporosis and are sometimes treated with spinal interbody fusion surgery. Previous studies have demonstrated the efficacy of strontium ranelate (SrR) treatment of osteoporosis in improving bone strength, promoting bone remodeling, and reducing the risk of fractures, but its effects on interbody fusion surgery have not been adequately investigated. SrR-treated rats subjected to interbody fusion surgery exhibited significantly higher lumbar vertebral bone mineral density after 12 weeks of treatment than rats subjected to the same surgery but not treated with SrR. Furthermore, histological and radiographic assessments showed that a greater amount of newly formed bone tissue was present and that better fusion union occurred in the SrR-treated rats than in the untreated rats. Taken together, these results show significant differences in bone mineral density, PINP level, histological score, SrR content and mechanical testing, which demonstrate a relatively moderate effect of SrR treatment on bone strength and remodeling in the specific context of recovery after an interbody fusion surgery, and suggest the potential of SrR treatment as an effective adjunct to spinal interbody fusion surgery for human patients.

  14. Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

    Directory of Open Access Journals (Sweden)

    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.

  15. Efeitos antinociceptivos e sedativos da buprenorfina, da acepromazina ou da associação buprenorfina e acepromazina em gatos Antinociceptive and sedative effects of buprenorphine, acepromazine, or combination of both, in conscious cats

    Directory of Open Access Journals (Sweden)

    Luciana Alvarez Santana

    2010-10-01

    Full Text Available O efeito antinociceptivo da buprenorfina tem sido relatado em cães e gatos. No presente estudo, avaliou-se o limiar nociceptivo mecânico em felinos tratados com buprenorfina, acepromazina ou ambas associadas e foram comparados os efeitos antinociceptivos e sedativos da associação em relação ao uso isolado desses fármacos determinados pelo mesmo observador, por meio de analgesiômetro e da escala analógica visual dinâmica interativa (DIVAS, respectivamente. Os oito animais empregados no estudo foram previamente familiarizados com os procedimentos utilizados. Após quatro mensurações basais, foram administrados, por via intramuscular, 0,02mg kg-1 de buprenorfina, 0,06mg kg-1 de acepromazina ou 0,01mg kg-1 de buprenorfina associada a 0,03mg kg-1 de acepromazina, em um estudo cego, com delineamento em quadrado latino e tratamento semanal. Os efeitos antinociceptivos e sedativos foram avaliados aos 15, 30, 45 minutos e uma, duas, três, quatro, seis, oito e 12 horas após a administração do tratamento. O limiar nociceptivo mecânico se elevou significativamente apenas no grupo tratado com a associação buprenorfina-acepromazina (entre 45 minutos e uma hora. Em relação à sedação, nos grupos tratados com acepromazina e com a associação, os valores da DIVAS foram significativamente maiores, respectivamente, de 15 minutos até quatro horas e de 15 minutos até três horas pós-tratamento, não apresentando elevação desses valores com a buprenorfina. Concluiu-se que não foi possível verificar a superioridade da neuroleptoanalgesia em relação ao uso dos fármacos isoladamente.The antinociceptive effects of buprenorphine have been reported in dogs and cats. This study evaluated changes in the mechanical nociceptive threshold and the sedative effects of buprenorphine, acepromazine and its combination in cats, determined by the same observer using a nociceptive threshold testing device and DIVAS, respectively. Eight animals were

  16. Evaluation of antinociceptive activity of aqueous extract of bark of psidium guajava in albino rats and albino mice.

    Science.gov (United States)

    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.

  17. Effects of Gelofusine Infusion Applied Before Spinal Anaesthesia on Hypotension and Coagulation

    Directory of Open Access Journals (Sweden)

    Sedat Kaya

    2006-01-01

    Full Text Available Hypotension is one of the most important complications of spinal anaesthesia. Hypotension may cause catastrophic side effects in hemodynamically unstable and/or old patients. Gelofusine has been used widely for many years for volume replacement therapies. But, it has disadvantages such as coagulopathy or trombositopenia.The aim of this study was to compare three different doses of gelofusine applied prophylactically before spinal anaesthesia for prevention of hypotension induced by spinal anaesthesia.The study was implemented 45 American Society of Anaesthesiologist physical status I-II orthopaedic patients. Fourty-five patients were allocated randomly into three groups. Gelofusine 5,10,15 mg/kg were infused intravenously in15 minutes in Group I,II and III respectively. Hypotension was observed in one patient for each group, which were treated with efedrin. Gelofusine prevented hypotension successfully in all three doses. Moreover, even the dose of 15mg/kg cause neither coagulopathy nor trombositopenia.We concluded that 5 mg/kg gelofusine is enough to avoid hypotension. Infusion of gelofusine in up to15 mg/kg was found to be safe for spinal anaesthesia; it does not have such side effect as coagulopathy or trombositopenia this doses.

  18. Delivery System For Mefenamic Acid Based On The Nanocarrier Layered Double Hydroxide: Physicochemical Characterization And Evaluation Of Anti-inflammatory And Antinociceptive Potential

    OpenAIRE

    Cunha; Vanessa R. R.; Guilherme; Viviane A.; de Paula; Eneida; de Araujo; Daniele R.; Silva; Renan O.; Medeiros; Jand V. R.; Leite; Jose R. S. A.; Petersen; Philippe A. D.; Foldvari; Marianna; Petrilli; Helena M.; Constantino; Vera R. L.

    2016-01-01

    Purpose: The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays. Methods: The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays. Results: In vivo assa...

  19. Effects of expiratory muscle activation via high-frequency spinal cord stimulation.

    Science.gov (United States)

    Kowalski, K E; Romaniuk, J R; Kowalski, T; DiMarco, A F

    2017-12-01

    In persons with spinal cord injury, lower thoracic low-frequency spinal cord stimulation (LF-SCS; 50 Hz, 15 mA) is a useful method to restore an effective cough. Unfortunately, the high-stimulus-amplitude requirements and potential activation of pain fibers significantly limit this application in persons with intact sensation. In this study, the mechanism of the expiratory muscle activation, via high-frequency SCS (HF-SCS; 500 Hz, 1 mA) was evaluated in dogs. In group 1, the effects of electrode placement on airway pressure generation (P) was evaluated. Maximal P occurred at the T9-T10 level with progressive decrements in P at more rostral and caudal levels for both LF-SCS and HF-SCS. In group 2, electromyographic (EMG) latencies of internal intercostal muscle (II) activation were evaluated before and after spinal root section and during direct motor root stimulation. Onset time of II EMG activity during HF-SCS was significantly longer (3.84 ± 1.16 ms) than obtained during direct motor root activation (1.61 ± 0.10 ms). In group 3, P and external oblique (EO) EMG activity, before and after sequential spinal section at the T11-T12 level, were evaluated. Bilateral dorsal column section significantly reduced EO EMG activity below the section and resulted in a substantial fall in P. Subsequent lateral funiculi section completely abolished those activities and resulted in further reductions in P. We conclude that 1) activation of the expiratory muscles via HF-SCS is dependent entirely on synaptic spinal cord pathways, and 2) HF-SCS at the T9 level produces a comparable level of muscle activation with that achieved with LF-SCS but with much lower stimulus amplitudes. NEW & NOTEWORTHY The findings in the present study suggest that lower thoracic high-frequency spinal cord stimulation with low stimulus currents results in sufficient activation of the expiratory muscles via spinal circuitry to produce large positive airway pressures sufficient to generate an

  20. Mechanisms involved in antinociception induced by a polysulfated fraction from seaweed Gracilaria cornea in the temporomandibular joint of rats.

    Science.gov (United States)

    Coura, Chistiane Oliveira; Chaves, Hellíada Vasconcelos; do Val, Danielle Rocha; Vieira, Lorena Vasconcelos; Silveira, Felipe Dantas; Dos Santos Lopes, Fernanda Maxcynne Lino; Gomes, Francisco Isaac Fernandes; Frota, Annyta Fernandes; Souza, Ricardo Basto; Clemente-Napimoga, Juliana Trindade; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2017-04-01

    Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K(+)ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K(+)ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by μ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K(+)ATP channel pathway, besides of HO-1. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Synthesis, Anti-inflammatory and Anti-nociceptive Evaluation of ...

    African Journals Online (AJOL)

    Synthesis, Anti-inflammatory and Anti-nociceptive Evaluation of Palmitoyl Benzamides. H Baba, CO Usifoh, PO Igbinaduwa. Abstract. Purpose: To synthesize and characterize palmitoyl amino benzamides, and to evaluate them for possible anti-inflammatory and anti-nociceptive activities. Methods: Palmitoyl amino ...

  2. Esmolol modulates inhibitory neurotransmission in the substantia gelatinosa of the spinal trigeminal nucleus of the rat

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    Kato Fusao

    2011-09-01

    Full Text Available Abstract Background β1-adrenaline receptor antagonists are often used to avoid circulatory complications during anesthesia in patients with cardiovascular diseases. Of these drugs, esmolol, a short-acting β antagonist, is also reported to exert antinociceptive and anesthetic sparing effects. This study was designed to identify the central mechanism underlying the antinociceptive effect of esmolol. Methods Wistar rats (7-21 d, 17-50 g were anesthetized with ketamine (100-150 mg/kg or isoflurane (5% and decapitated. Horizontal slices (400-μm thick of the lower brainstem containing the substantia gelatinosa (SG of the caudal part of the spinal trigeminal nucleus (Sp5c, in which the nociceptive primary afferents form the first intracranial synapses, were made with a vibrating slicer. The miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs, respectively were simultaneously recorded from visually identified SG neurons of the Sp5c in the presence of tetrodotoxin (1 μM. Additionally, mIPSCs were recorded during pharmacological isolation of GABA- and glycine-mediated mIPSCs with kynurenic acid (1 mM. Results Esmolol (500 μM significantly and selectively increased the mIPSC frequency (to 214.2% ± 34.2% of the control, mean ± SEM, n = 35; P 2+. Conclusions These data suggest that esmolol modulates inhibitory transmitter release in the Sp5c through a mechanism involving Ca2+-entry but in a β1-adrenoceptor-independent manner. The present results suggest that the facilitation of inhibitory transmitter release in the central nociceptive network underlies, at least in part, the antinociceptive effect of esmolol.

  3. Investigating the Effects of Adding Fentanyl to Bupivacaine in Spinal Anesthesia of Opium-addicted Patients

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    H Satari

    2014-10-01

    Full Text Available Introduction: Spinal anesthesia in opium-addicted patients can be associated with many complications. Hence, this study aimed to investigate sensory and motor block characteristics, duration of postoperative analgesia, hemodynamic and side effects by adding Fentanyl to bupivacaine in spinal Anesthesia of opium-addicted patients. Methods: In a double-blind randomized clinical trial, 60 American society of Anesthesiology (ASA class I and II opium-addicted patients under spinal anesthesia in lower abdominal and lower limb operations were randomly classified into two groups of spinal anesthesia with bupivacaine and bupivacaine-fentanyl. Clinical symptoms, side effects, the duration of sensory and motor block, initiation of analgesia requirement and sensory block were assessed. Results: The study results indicated no significant difference between bupivacaine and bupivacaine-fentanyl groups in regard with demographic, side effects, blood pressure and heart rate, though a significant difference was observed in respiratory rate 5min, 10min, 45min, 75min and 90 min after block. Duration of sensory (100.33 to 138.83 and motor block (93.43 to 107.66 and , initiation of analgesia requirement (165.33 to 187.76 was significantly longer in bupivacaine-fentanyl, though initiation of sensory block (8.83 to 4.93 was significantly longer in bupivacaine. Conclusion: Addition of fentanyl to bupivacaine in spinal anesthesia increases the duration of sensory and motor block and initiation of analgesia requirement in opium-addicted patients and also decreases initiation of sensory block in these patients.

  4. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon.

    Science.gov (United States)

    da Silva, Juliana Almeida; Biagioni, Audrey Francisco; Almada, Rafael Carvalho; de Souza Crippa, José Alexandre; Cecílio Hallak, Jaime Eduardo; Zuardi, Antônio Waldo; Coimbra, Norberto Cysne

    2015-07-05

    Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Neuronal plasticity after a human spinal cord injury: positive and negative effects.

    Science.gov (United States)

    Dietz, Volker

    2012-05-01

    In patients suffering an incomplete spinal cord injury (SCI) an improvement in walking function can be achieved by providing a functional training with an appropriate afferent input. In contrast, in immobilized incomplete and complete subjects a negative neuroplasticity leads to a neuronal dysfunction. After an SCI, neuronal centers below the level of lesion exhibit plasticity that either can be exploited by specific training paradigms or undergo a degradation of function due to the loss of appropriate input. Load- and hip-joint-related afferent inputs seem to be of crucial importance for the generation of a locomotor pattern and, consequently, the effectiveness of the locomotor training. In severely affected SCI subjects rehabilitation robots allow for a longer and more intensive training and can provide feedback information. Conversely, in severely affected chronic SCI individuals without functional training the locomotor activity in the leg muscles exhausts rapidly during assisted locomotion. This is accompanied by a shift from early to dominant late spinal reflex components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete SCI. It is assumed that in chronic SCI the patient's immobility results in a reduced input from supraspinal and peripheral sources and leads to a dominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and spinal reflex generation. A training with an enhancement of an appropriate proprioceptive input early after an SCI might serve as an intervention to prevent neuronal dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

    Science.gov (United States)

    Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

    1988-01-01

    Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

  7. Protective effect of melatonin against spinal cord injury from seawater immersion in rabbits

    Directory of Open Access Journals (Sweden)

    Tao WANG

    2017-04-01

    Full Text Available Objective  To observe the protective effects of melatonin against spinal cord injury from seawater immersion in rabbits. Methods  The 120 mature and health New Zealand White rabbits, weight range from 2.6 to 2.9kg, were randomly divided into four groups (30 each: control group, ethanol group, melatonin group (100mg/kg, methylprednisolone group (30mg/kg. The rabbit model of spinal cord injury were built by modified Allen's method taking the 10th thoracic vertebra as a center, seawater immersion for 60 minutes, and then by grouping to give the appropriate treatment. After each group was given the corresponding treatment, six rabbits in each group were randomly selected at 1, 6, 12, 24 and 48 hours five different time points. The neurological function scores of the rabbits were evaluated by Tarlov method, the spinal cord of T9 to T11 which were obtained from all the groups were used for further study, including immunohistochemical detection of apoptosis proteins: Bax, Bcl-2, neurofilament protein 200 (NF200 and in situ end labeling (TUNEL method to detect spinal neuronal cell apoptosis. Results  Within each observation time point, the Tarlov score was higher in melatonin group and methylprednisolone group compared with control group and ethanol group (P0.05. The expressions of Bcl-2 and NF200 were significantly higher in melatonin group and methylprednisolone group compared with control group and ethanol group, while Bax expression was significantly lower (P0.05. The TUNEL-positive apoptotic cells were fewer in melatonin group and methylprednisolone group compared with control group and ethanol group (P0.05. Conclusion  Melatonin has protective effect against spinal cord injury from seawater immersion in rabbits, no difference in effcacy exists compare with methylprednisolone. DOI: 10.11855/j.issn.0577-7402.2017.02.08

  8. Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

    Science.gov (United States)

    Ahmed, Zaghloul

    2017-10-01

    Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

  9. The effect of electrical passive cycling on spasticity in war veterans with SCI (Spinal Cord Injury)

    OpenAIRE

    Rayegani, Seyed M; Hadi eShojaee; Leyla eSedighipour; Mohammad Reza eSoroush; Mohmmad eBaghbani; Omm’Ol Banin eAmirani

    2011-01-01

    Introduction: Muscle atrophy, spasticity and deformity are among long term complication of Spinal Cord Injury(SCI) veterans. There are numerous studies evaluating effect of functional electrical stimulation (FES) on muscle properties of SCI people, but less research has focused on the benefits of passive cycling in the management of spasm and improving ROM of lower limbs in individuals with SCI. Aims: To evaluate the effect of electrical passive cycling on passive range of movement spasticit...

  10. The Effect of Electrical Passive Cycling on Spasticity in War Veterans with Spinal Cord Injury

    OpenAIRE

    Rayegani, Seyed Mansoor; Shojaee, Hadi; Sedighipour, Leyla; Soroush, Mohammad Reza; Baghbani, Mohammad; Amirani, Omm’ol Banin

    2011-01-01

    Introduction: Muscle atrophy, spasticity, and deformity are among long term complication of spinal cord injury (SCI) veterans. There are numerous studies evaluating effect of functional electrical stimulation on muscle properties of SCI people, but less research has focused on the benefits of passive cycling in the management of spasticity and improving ROM of lower limbs in individuals with SCI. Aims: To evaluate the effect of electrical passive cycling on passive range of movement spasticit...

  11. Antinociceptive and anti-inflammatory potential of Rhododendron arboreum bark.

    Science.gov (United States)

    Nisar, Muhammad; Ali, Sajid; Muhammad, Naveed; Gillani, Syed N; Shah, Muhmmad R; Khan, Haroon; Maione, Francesco

    2016-07-01

    Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments.The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions.The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50-200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1-5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by in vitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases. © The Author(s) 2014.

  12. Comparison of the effects and complications of unilateral spinal anesthesia versus standard spinal anesthesia in lower-limb orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Seyyed Mostafa Moosavi Tekye

    2014-06-01

    Full Text Available Introduction: A restricted sympathetic block during spinal anesthesia may minimize hemodynamic changes. This prospective randomized study compared unilateral and bilateral spinal anesthesia with respect to the intra- and postoperative advantages and complications of each technique. Material and methods: Spinal anesthesia was induced with 0.5% hyperbaric bupivacaine and a 25-G Quincke needle (Dr. J in two groups of patients with physical status ASA I-II who had been admitted for orthopedic surgeries. In group A, dural puncture was performed with the patient in a seated position using 2.5 cm3 of hyperbaric bupivacaine. Each patient was then placed in the supine position. In group B, dural puncture was performed with the patient in the lateral decubitus position with 1.5 cm3 of hyperbaric bupivacaine. The lower limb was the target limb. The speed of injection was 1 mL/30 s, and the duration of time spent in the lateral decubitus position was 20 min. Results: The demographic data were similar in both groups. The time to the onset of the sensory and motor block was significantly shorter in group A (p = 0.00. The duration of motor and sensory block was shorter in group B (p < 0.05. The success rate for unilateral spinal anesthesia in group B was 94.45%. In two patients, the spinal block spread to the non-dependent side. The incidence of complications (nausea, headache, and hypotension was lower in group B (p = 0.02. Conclusion: When unilateral spinal anesthesia was performed using a low-dose, low-volume and low-flow injection technique, it provides adequate sensory-motor block and helps to achieve stable hemodynamic parameters during orthopedic surgery on a lower limb. Patients were more satisfied with this technique as opposed to the conventional approach. Furthermore, this technique avoids unnecessary paralysis on the non-operated side.

  13. Evidence for the Involvement of Spinal Cord-Inhibitory and Cytokines-Modulatory Mechanisms in the Anti-Hyperalgesic Effect of Hecogenin Acetate, a Steroidal Sapogenin-Acetylated, in Mice

    Directory of Open Access Journals (Sweden)

    Jullyana S.S. Quintans

    2014-06-01

    Full Text Available Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as ‘sisal’, and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA is a steroidal sapogenin-acetylated that produces antinociceptive activity. Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile. Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p. inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1β. The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms.

  14. Antinociceptive activity of the ethanolic extract of the root bark of ...

    African Journals Online (AJOL)

    Both morphine (1 - 5 mg/kg, i.p.) and C. sieberiana extract (10 - 40 mg/kg, p.o.) caused dose-dependent anti-nociceptive effects in rats on the hotplate. The mean maximal analgesic effects occurred 30 minutes after administration of either morphine (1 - 5 mg/kg, i.p.) or extract. There was no statistical difference between the ...

  15. Antinociceptive activity of the volatile oils of Hyptis pectinata L. Poit. (Lamiaceae) genotypes.

    Science.gov (United States)

    Arrigoni-Blank, M F; Antoniolli, A R; Caetano, L C; Campos, D A; Blank, A F; Alves, P B

    2008-05-01

    Hyptis pectinata L. Poit (Lamiaceae) is known popularly in Brazil as "sambacaita" or "canudinho" and is used in the treatment of inflammations, bacterial infections and ache. The antinociceptive activity of the volatile oils of six genotypes, at doses of 100, 200 and 400mg/kg body wt., were investigated using abdominal writhe models induced by acetic acid and hot plate tests. The volatile oils of all the genotypes are composed mainly of sesquiterpenoids. All the genotypes showed antinociceptive effects in both models used; the SAM002 genotype showed the major inhibitory effect at dose of 100mg/kg body wt. These results suggest that the volatile oil of H. pectinata has peripheral (writhe reduction) and central (time delay of thermal reaction) effects. These observations indicate that H. pectinata may be useful as an analgesic drug.

  16. Cost effectiveness analysis of graft options in spinal fusion surgery using a Markov model.

    Science.gov (United States)

    Virk, Sohrab; Sandhu, Harvinder S; Khan, Safdar N

    2012-10-01

    Statistical decision model. To determine the most cost-effective graft option in spinal fusion. Spinal fusion has been shown to be an effective technique to treat lumbar degenerative spondylolisthesis. There have been significant advances in bone graft options to improve outcomes related to spinal fusion. RhBMP-2 (RhBMP), iliac crest bone graft (ICBG), local bone alone (LBG), demineralized bone matrix with local bone (DBM), local bone with corticocancellous allograft chips (CCA) have all been used as graft options. There has not been significant research in which graft option is most cost effective. A Markov decision model has been created to identify the most cost-effective graft option for use in spinal fusion to treat 1-level (L4-L5) degenerative spondylolisthesis in a cohort of 60-year-old patients. Costs and effectiveness of successful spinal fusion surgery and revision surgery associated with each graft option was estimated through published data. The quality adjusted life years (QALYs) from these surgeries were compared with the amount of QALYs associated with living with chronic back pain. : In the base case, the incremental cost-effective ratio for each graft option when compared with living with chronic back pain was $21,308/QALY for ICBG, $16,595/QALY for RhBMP, $21,204/QALY for LBG, $21,287/QALY for DBM, and $28,153/QALY for CCA. Therefore, the most cost-effective graft option in the base case was RhBMP. Sensitivity analysis shows that RhBMP is not the most cost-effective option if the revision rate is significantly raised. If the cost of treatment with RhBMP rises >$42,250 then LBG becomes the likely cost-effective treatment. RhBMP is the most cost-effective graft option for L4-L5 fusion for degenerative spondylolisthesis largely due to the reduced rate of revision spine surgery. The increased upfront cost and list of complications associated with RhBMP is offset by the reduced rate of revision surgery.

  17. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

    Directory of Open Access Journals (Sweden)

    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.

  18. Increased spinal reflex excitability is not associated with neural plasticity underlying the cross-education effect.

    Science.gov (United States)

    Lagerquist, Olle; Zehr, E Paul; Docherty, David

    2006-01-01

    The purpose of this study was to examine the effects of a 5-wk unilateral, isometric strength-training program on plasticity in the spinal Hoffmann (H-) reflex in both the trained and untrained legs. Sixteen participants, 22-42 yr old, were assigned to either a control (n = 6) or an exercise group (n = 10). Both groups were tested for plantar flexion maximal voluntary isometric contractions (MVIC) and soleus H-reflex amplitude in both limbs, at the beginning and at the end of a 5-wk interval. Participants in the exercise group showed significantly increased MVIC in both legs after training (P cross-education effect of strength training may be due to supraspinal to a greater extent than spinal mechanisms.

  19. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease)

    DEFF Research Database (Denmark)

    Preisler, N; Andersen, G; Thøgersen, F

    2009-01-01

    OBJECTIVE: We examined the effect of aerobic exercise in patients with spinal and bulbar muscular atrophy (SBMA). SBMA is caused by a defect androgen receptor. This defect causes motor neuron death, but considering the important function of androgens in muscle, it is possible that muscle damage...... in SBMA also occurs independently of motor neuron damage. METHODS: Eight patients with SBMA engaged in regular cycling exercise for 12 weeks. Maximum oxygen uptake (Vo(2max)), maximal work capacity (W(max)), muscle morphology, citrate synthase (CS) activity, body composition, EMG, static strength......) or any of the other variables examined before and after training, and the patients with SBMA did not feel improvements in ADL. CONCLUSIONS: Frequent, moderate-intensity aerobic conditioning is of little beneficial effect in patients with spinal and bulbar muscular atrophy (SBMA). High levels of plasma...

  20. Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

    Science.gov (United States)

    Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

    2014-08-01

    Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; pbrain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

  1. Effects of Local Administration of Boric Acid on Posterolateral Spinal Fusion with Autogenous Bone Grafting in a Rodent Model.

    Science.gov (United States)

    Kömürcü, Erkam; Özyalvaçlı, Gülzade; Kaymaz, Burak; Gölge, Umut Hatay; Göksel, Ferdi; Cevizci, Sibel; Adam, Gürhan; Ozden, Raif

    2015-09-01

    Spinal fusion is among the most frequently applied spinal surgical procedures. The goal of the present study was to evaluate whether the local administration of boric acid (BA) improves spinal fusion in an experimental spinal fusion model in rats. Currently, there is no published data that evaluates the possible positive effects if the local administration of BA on posterolateral spinal fusion. Thirty-two rats were randomly divided into four independent groups: no material was added at the fusion area for group 1; an autogenous morselized corticocancellous bone graft was used for group 2; an autogenous morselized corticocancellous bone graft with boric acid (8.7 mg/kg) for group 3; and only boric acid was placed into the fusion area for group 4. The L4-L6 spinal segments were collected at week 6, and the assessments included radiography, manual palpation, and histomorphometry. A statistically significant difference was determined between the groups with regard to the mean histopathological scores (p = 0.002), and a paired comparison was made with the Mann-Whitney U test to detect the group/groups from which the difference originated. It was determined that only the graft + BA practice increased the histopathological score significantly with regard to the control group (p = 0.002). Whereas, there was no statistically significant difference between the groups in terms of the manual assessment of fusion and radiographic analysis (respectively p = 0.328 and p = 0.196). This preliminary study suggests that BA may clearly be useful as a therapeutic agent in spinal fusion. However, further research is required to show the most effective dosage of BA on spinal fusion, and should indicate whether BA effects spinal fusion in the human body.

  2. Evaluation of antinociceptive and antimicrobial activities of galbanum plant (Ferula gumosa Boiss

    Directory of Open Access Journals (Sweden)

    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.

  3. Spinal cord deformation due to nozzle gas flow effects using optical coherence tomography

    Science.gov (United States)

    Wong, Ronnie J.; Jivraj, Jamil; Vuong, Barry; Ramjist, Joel; Sun, Cuiru; Huang, Yize; Yang, Victor X. D.

    2015-03-01

    The use of gas assistance in laser machining hard materials is well established in manufacturing but not in the context of surgery. Laser cutting of osseous tissue in the context of neurosurgery can benefit from gas-assist but requires an understanding of flow and pressure effects to minimize neural tissue damage. In this study we acquire volumetric flow rates through a gas nozzle on the spinal cord, with dura and without dura.

  4. A study to compare the effect of spinal manipulation versus mobilization on hamstring muscle strength

    OpenAIRE

    2013-01-01

    M.Tech. (Chiropractic) Purpose: This study aims to compare the effects of spinal manipulation versus mobilization of the lumbar spine and sacroiliac (SI) joints on the contractile strength of the hamstring muscle group with regards to strength and flexibility. Method: This study consisted of 2 groups of 15 participants between the ages of 18 and 50 years of age. Males and females were first separated to ensure equal male to female ratios within each group. The potential participants were e...

  5. Effective Body Cooling Method for Persons with Spinal Cord Injury during Exercise

    OpenAIRE

    山崎, 昌廣; 長谷川, 博; 高取, 直志; 金, 奎兌

    2003-01-01

    The purpose of this study was to clarify the effects of water ingestion and wearing a cooling jacket on thermoregulatory responses during arm cranking exercise in persons with spinal cord injury. Six male paraplegics (Li - Th6) exercised for 30 min at 20 watts in a hot environment (33 °C, 80% relative humidity) under three separate conditions; no drinking (ND), water ingestion (D) and water ingestion with wearing cooling jacket (DJ). Tympanic membrane temperature (Tty), skin temperature and h...

  6. EFFECTIVENESS OF FLOOR EXERCISES VERSES BALL EXERCISES ON SPINAL MOBILITY IN SPASTIC DIPLEGIC

    OpenAIRE

    Sumitra Sakhawalkar; Sayli Paldhikar; Priya Chitre; Snehal Ghodey

    2017-01-01

    Background: The objective of this present study was to determine the Effectiveness of Floor Exercises versus Ball Exercises on spinal mobility in Spastic Diplegic. Methods: Institutional ethical committee permission was taken before starting the study. A sample of 70 Diplegic CP children was screened, and 40 meeting the inclusion criteria were selected for study were then randomly divided into two groups one control other experimental i.e. 20 in each group by chit method. Both the grou...

  7. Steady-streaming effects on the motion of the cerebrospinal fluid (CSF) in the spinal canal

    Science.gov (United States)

    Lawrence, Jenna; Coenen, Wilfried; Sanchez, Antonio; Lasheras, Juan

    2017-11-01

    With each heart beat the oscillatory blood supply to the rigid cranial vault produces a time-periodic variation of the intracranial pressure that drives the cerebrospinal fluid (CSF) periodically in and out of the compliant spinal canal. We have recently conducted an analysis of this flow-structure interaction problem taking advantage of the small compliance of the dura membrane bounding externally the CSF and of the disparity of length scales associated with the geometry of the subarachnoid space. We have shown in an idealized geometry that the steady-streaming motion associated with this periodic flow, resulting from the nonlinear cumulative effects of convective acceleration, causes a bulk recirculation of CSF inside the spinal canal, which has been observed in many radiological studies. We extend here our study to investigate the possible contribution arising from the flow around the nerve roots protruding from the spinal cord, an effect that was neglected in our previous work. For this purpose, we consider the oscillatory motion around a cylindrical post confined between two parallel plates. For large values of the relevant Strouhal number we find at leading order a harmonic Stokes flow, whereas steady-streaming effects enter in the first-order corrections, which are computed for realistic values of the Womersley number and of the cylinder height-to-radius ratio.

  8. In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

    Science.gov (United States)

    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.

  9. Decreased endomorphin-2 and opioidreceptor in the spinal cord are associated with painful diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Zhen-Zhen Kou

    2016-09-01

    Full Text Available Painful diabetic neuropathy (PDN is one of the most common complications in the early stage of diabetes mellitus (DM. Endomorphin-2 (EM2 selectively activates the opioid receptor (MOR and subsequently induces antinociceptive effects in the spinal dorsal horn. However, the effects of EM2-MOR in PDN have not yet been clarified in the spinal dorsal horn. Therefore, we aimed to explore the role of EM2-MOR in the pathogenesis of PDN. The main findings were the following: (1 streptozotocin (STZ-induced diabetic rats exhibited hyperglycemia, body weight loss and mechanical allodynia; (2 in the spinal dorsal horn, the expression levels of EM2 and MOR decreased in diabetic rats; (3 EM2 protein concentrations decreased in the brain, lumbar spinal cord and CSF in diabetic rats but were unchanged in the plasma; (4 the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs was significantly higher in diabetic rats than in control rats; and (5 intrathecal injection of EM2 for 14 days in the early stage of PDN partially alleviated mechanical allodynia and reduced MOR expression in diabetic rats. Our results demonstrate that the EM2-MOR signal may be involved in the early stage of PDN.

  10. Analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd.

    Science.gov (United States)

    Barua, Chandana Choudhury; Roy, Jayanti Datta; Buragohain, Bhaben; Barua, Acheenta Gohain; Borah, Prabodh; Lahkar, Mangala

    2011-04-01

    To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd. Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice), Eddy's hot plate (mice) and tail flick model (rat) for analgesic study and formalin-induced paw licking model (mice) were used for anti-nociceptive study. In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.). DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future.

  11. Antinociceptive activity of Buddleja globosa (matico) in several models of pain.

    Science.gov (United States)

    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.

  12. Spinal Stenosis

    Science.gov (United States)

    ... and allows you to stand and bend. Spinal stenosis causes narrowing in your spine. The narrowing puts ... and spinal cord and can cause pain. Spinal stenosis occurs mostly in people older than 50. Younger ...

  13. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans

    Science.gov (United States)

    Rejc, Enrico; Angeli, Claudia; Harkema, Susan

    2015-01-01

    Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs’ muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25–60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical. PMID:26207623

  14. Coadministration of Dexamethasone and Melissa officinalis Has Neuroprotective Effects in Rat Animal Model with Spinal Cord Injury.

    Science.gov (United States)

    Hosseini, Seyed Ruhollah; Kaka, Gholamreza; Joghataei, Mohammad Taghi; Hooshmandi, Mehdi; Sadraie, Seyed Homayoon; Yaghoobi, Kayvan; Mansoori, Korosh; Mohammadi, Alireza

    2017-01-01

    Spinal cord injury (SCI) causes inflammation, deformity and cell loss. It has been shown that Melissa officinalis (MO), as herbal medicine, and dexamethasone (DEX) are useful in the prevention of various neurological diseases. The present study evaluated combinational effects of DEX and MO on spinal cord injury. Thirty six adult male Wistar r