rats; analgesic activity with doses of 280 mg/kg and 560 mg/kg, p.o., was evaluated by hot plate method and acetic acid induced writhing method in Swiss albino mice; and antipyretic activity with doses of 110 mg/kg and 220 mg/kg, p.o., was evaluated in New Zealand white rabbits by injecting gram –ve lipopolysaccharide ...
Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J
studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...... may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain....
Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J
studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...... may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain....
Full Text Available Abstract Objectives The reduction of pain due to routine invasive procedures (capillary heel stick blood sampling for neonatal metabolic screening in the newborn is an important objective for the so-called "Hospital with no pain". Practices such as skin to skin contact, or breastfeeding, in healthy newborn, may represent an alternative to the use of analgesic drugs. The aim of our work is to evaluate the analgesic effect of breastfeeding during heel puncture in full term healthy newborn. Methods We studied 200 healthy full term newborns (100 cases and 100 controls, proposing the puncture to mothers during breastfeeding, and explaining to them all the advantages of this practice. Pain assessment was evaluated by DAN scale (Douleur Aigue Nouveau ne scale. Results The difference in score of pain according to the DAN scale was significant in the two groups of patients (p = 0.000; the medium score was 5.15 for controls and 2.65 for cases (newborns sampled during breastfeeding. Conclusion Our results confirmed the evidence of analgesic effect of breastfeeding during heel puncture. This procedure could easily be adopted routinely in maternity wards.
Sanaz Mahdipour; Samaneh Teimouri; Omid Reza Tamtaji; Mojgan Mohammadifar; Mohsen Taghizadeh; Sayyed Alireza Talaei
Abstract Background: Neuropathic pain is a chronic pain that affects on the patient’s quality of life. Use of herbal instead of synthetic drugs recently has been increased due to side effects of synthetic drugs and herbal effective components. Flavonoids are herbal compounds that have analgesic and anti-inflammatory effects. Because Allium cepa L. has a great amount of flavonoids, this study has been designed to evaluate analgesic effects of alcoholic extract of Allium cepa L. on neuropath...
Monti, Ludovica; Stefanucci, Azzurra; Pieretti, Stefano; Marzoli, Francesca; Fidanza, Lorenzo; Mollica, Adriano; Mirzaie, Sako; Carradori, Simone; De Petrocellis, Luciano; Schiano Moriello, Aniello; Benyhe, Sándor; Zádor, Ferenc; Szűcs, Edina; Ötvös, Ferenc; Erdei, Anna I; Samavati, Reza; Dvorácskó, Szabolcs; Tömböly, Csaba; Novellino, Ettore
Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.
Al-Suwayeh, Saleh A; Taha, Ehab I; Al-Qahtani, Fahad M; Ahmed, Mahrous O; Badran, Mohamed M
The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.
Saleh A. Al-Suwayeh
Full Text Available The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC and carbopol. The carbopol gels in presence of propylene glycol (PG and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD, beta-cyclodextrin (β-CD, Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8 showed the highest flux (14.31 μg/cm2/h with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8 enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo. This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.
Olesen, Anne Estrup; Andresen, Trine; Christrup, Lona Louring
facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic studies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical...... analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information regarding a given drug substance and its effects can be obtained. Results from experimental human visceral pain research can bridge the gap in knowledge between animal......Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can...
Full Text Available Abstract Background: Neuropathic pain is a chronic pain that affects on the patient’s quality of life. Use of herbal instead of synthetic drugs recently has been increased due to side effects of synthetic drugs and herbal effective components. Flavonoids are herbal compounds that have analgesic and anti-inflammatory effects. Because Allium cepa L. has a great amount of flavonoids, this study has been designed to evaluate analgesic effects of alcoholic extract of Allium cepa L. on neuropathic pain behavior in chronic constriction injury model in rats. Materials and Methods: In this experimental study, neuropathic pain induced by chronic constriction injury (CCI model in Rats. Animals were randomly divided into 4 groups (n=10 for each: Sham, CCI model, receiving red onion hydroalcoholic extract at a dose of 100 mg/kg and a group receiving gabapentin (100 mg/kg. Red onion extract and gabapentin were administered by gavage for 21 days. Using thermal hyperalgesia, mechanical and thermal allodynia tests, the analgesic effects of extract have been measured. Results: Findings of this study revealed that CCI surgery on rats induced hyperalgesia, mechanical and thermal allodynia. Daily intakes of alcoholic extract of red onion and gabapentin significantly increase the paw withdrawal latency; increase the threshold to mechanical allodynia and decrease in response to acetone. Conclusion: Oral use of alcoholic extract of Allium cepa L. reduces neuropathic pain behavior in CCI model in rats.
paracetamol (acetaminophen), aspirin and indomethacin while VII received saline water. Thirty minutes observation ... 4.07 and 40.00 ± 2.08) compared to paracetamol, aspirin, indomethacin (76.50±7.64, 45.67± 2.73, 33.50 ±. 4.23) and saline water .... inhibitory potential on prostaglandin synthesis. The analgesic potency ...
Guevara-López, Uriah; Uscanga-Sánchez, Santos; Márquez, José; Bárcenas-Olivares, Juan; Martínez-Arenas, Angeles; Palma-Aguirre, José Antonio
The analgesic efficacy of intramuscular etofenamate (1 g/day) and intramuscular diclofenac (75 mg/day) was assessed in post-surgical pain relief during a period of 3 days. One hundred ten hospitalized patients undergoing elective surgery were evaluated in an open-label, comparative, randomized, parallel-group, multicenter study. Fifty five patients received etofenamate and 55 patients diclofenac, 1 h before surgery. The doses were administered after 24 and 48 h. Baseline evaluations were carried out 30 min after anesthesia recovery and the clinical efficacy variables were assessed at 1, 6, 12, 24, 36, 48, 60 and 72 h. The efficacy variables were Pain Visual-Analogue Scale (VAS), Pain Analogous Verbal Scale (AVERS), and Well-Being Scale. Adverse events were documented. Patients in both groups showed similar values in post-surgical pain relief (VAS, AVERS). According to VAS, etofenamate at 24 h had a better analgesic action than diclofenac even though it was not statistically significant. Both drugs demonstrated to be safe. Patients in both groups reported nausea, vomiting, flatulence, and pain at injection site. We find that both etofenamate and diclofenac were safe, tolerable, and effective treatments for the relief of post-surgical pain.
Hu, Helen H; MacAllister, Charles G; Payton, Mark E; Erkert, Ronald S
To compare analgesic effects of phenylbutazone administered at a dosage of 4.4 mg/kg/d (2 mg/lb/d) or 8.8 mg/kg/d (4 mg/lb/d) in horses with chronic lameness. Controlled crossover study. Animals-9 horses with chronic forelimb lameness. Horses were treated i.v. with phenylbutazone (4.4 mg/kg/d or 8.8 mg/kg/d) or saline (0.9% NaCl) solution once daily for 4 days. All horses received all 3 treatments with a minimum of 14 days between treatments. Mean peak vertical force (mPVF) was measured and clinical lameness scores were assigned before initiation of each treatment and 6, 12, and 24 hours after the final dose for each treatment. Compared with values obtained after administration of saline solution, mPVF was significantly increased at all posttreatment evaluation times when phenylbutazone was administered. Clinical lameness scores were significantly decreased 6 and 12 hours after administration of the final dose when phenylbutazone was administered at the low or high dosage but were significantly decreased 24 hours after treatment only when phenylbutazone was administered at the high dosage. No significant differences in mPVF and clinical lameness scores were found at any time when phenylbutazone was administered at the low versus high dosage. Results suggest that the high dosage of phenylbutazone was not associated with greater analgesic effects, in terms of mPVF or lameness score, than was the low dosage. Considering that toxicity of phenylbutazone is related to dosage, the higher dosage may not be beneficial in chronically lame horses.
Mitra Jabalameli; Forough Kalantari
Background: Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control. Materials and Methods: Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean. Inclusion criteria: Prime g...
Full Text Available Background and Objective: Pain is a complex process influenced by both physiological and psychological factors. In spite of an armamentarium of analgesic drugs and techniques available to combat post-operative pain, appropriate selection, and effective management for relief of post-operative pain still poses unique challenges. The discovery of peripheral opioid receptors has led to growing interest in the use of locally applied opioids (intra-articular, intra-pleural, intra-peritoneal, and perineural for managing acute pain. As bone graft harvesting is associated with significant post-operative pain and there is a paucity of literature on the use of peripheral opioids at the iliac crest bone harvesting site, the present study was planned to evaluate the analgesic efficacy of local administration of morphine after iliac crest bone graft harvesting. Materials and Methods: A total of 60 patients, 20-50 years of age scheduled to undergo elective surgery for delayed and non-union fracture both bone leg with bone grafting under general anaesthesia (GA were randomly assigned to one of the four groups of 15 patients each: group 1: 2.5 ml normal saline (NS +2.5 ml NS infiltrated into the harvest site at 2 sites + 1 ml NS intramuscularly (i/m; Group 2: 2.5 ml NS + 2.5 ml NS infiltrated into the harvest site at 2 sites + 5 mg morphine in 1 ml i/m.; Group 3: 2.5 mg (2.5 ml morphine + 2.5 mg (2.5 ml morphine infiltrated into the harvest site at 2 sites + 1 ml NS i/m; Group 4: 0.5 mg naloxone (2.5 ml +5 mg (2.5 ml morphine infiltrated into the harvest site at 2 sites + 1 ml NS i/m. Pain from the bone graft site and operative site was assessed for 24 h post-operatively. Results: The patients who had received morphine infiltration (Group 3 had significantly less pain scores at the graft site at 4, 6, and 10 post-operative hours. They also had significantly less morphine consumption and overall better pain relief as compared to the other groups. Conclusions
Full Text Available Background: Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control. Materials and Methods: Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean. Inclusion criteria: Prime gravid candidate of elective cesarean and spinal anesthesia class 1 or 2. Known case of drug allergy and methadone interaction, addiction, uncontrolled medical disease excluded. Case group injected 10 mg of subcutaneous methadone in the site of incision before final suture. Morphine was a pain reliever in follow up examination. Data include mean of pain, nausea and vomiting, MAP, etc., collected and analyzed by independent-T test and Man Whitney test. Results: Although mean usage of morphine between groups was not significant statistically but the mean pain severity (P value < 0.05 and mean satisfactory (P value = 0.02 was statistically significant between groups. Other parameters were not statistically significant. Conclusion: We suggest subcutaneous methadone as a safe pain reliever in post cesarean section patients.
Jabalameli, Mitra; Kalantari, Forough
Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control. Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean. Prime gravid candidate of elective cesarean and spinal anesthesia class 1 or 2. Known case of drug allergy and methadone interaction, addiction, uncontrolled medical disease excluded. Case group injected 10 mg of subcutaneous methadone in the site of incision before final suture. Morphine was a pain reliever in follow up examination. Data include mean of pain, nausea and vomiting, MAP, etc., collected and analyzed by independent-T test and Man Whitney test. Although mean usage of morphine between groups was not significant statistically but the mean pain severity (P value < 0.05) and mean satisfactory (P value = 0.02) was statistically significant between groups. Other parameters were not statistically significant. We suggest subcutaneous methadone as a safe pain reliever in post cesarean section patients.
Wagner, S A; Young, J M; Tena, J K; Manning, B H
The objective of this study was to evaluate the effect of flunixin meglumine treatment on lameness pain in dairy cows. Twenty-four lactating Holstein cows were enrolled in the study based on visual observation of abnormal locomotion. The primary measurement endpoint was weight-shifting between the rear limbs. Weight-shifting was calculated as the standard deviation of the weight borne on the rear limbs over a 15 min period; this value correlates directly with lameness pain in dairy cows. After collecting baseline weight-bearing data, we randomly assigned cows to 1 of 2 treatment groups: 2.2 mg/kg body weight flunixin meglumine (2 mL/45 kg) or an equivalent volume of isotonic sterile saline solution. Weight-bearing data were collected from each cow at 2, 6, 12, and 24 h after a single intravenous drug treatment. Mean locomotion scores over the 2 d before treatment were 2.38/5 in the flunixin-treated group and 2.43/5 in the saline-treated control group; these values were not significantly different. Weight-shifting values were also not significantly different on either pretreatment day. Cows treated with flunixin meglumine showed significantly less weight-shifting between the rear limbs at 6, 12, and 24 h after treatment compared with saline-treated controls, providing evidence that flunixin meglumine alleviates lameness-associated pain. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Nagalakshmi.R*, Surinder Kaur
The main objective of this research was to formulate an analgesic drug incorporated in topically used sticks, prepared using suitable ointment bases with varied concentrations of waxes, lubricants, surfactants, etc. and incorporation of medicament in the optimized formula by heating and congealing process. Indomethacin was the drug of choice used because; this drug if used orally has a lot of side effects which has to be reduced. The main purpose of this formulation was to dispense medicated ...
Full Text Available This study is to establish a model of rat tibial osteocarcinoma pain, intrathecally inject specific ERK1/2 inhibitors SCH772984, observe the analgesic effect, and discuss the influence of ERK-P90RSK-Fos signal path in bone cancer pain. Forty female SD rats were randomly divided into 5 groups. Establish a bone cancer pain model after putting the intrathecal tube 5d and determine the rats’ mechanical withdrawal threshold (MWT after tube 5d; 40 SD rats with intrathecal tube back 5d were randomly divided into 5 groups. Sham Group receives no medication, the other four respectively receive 5% DMSO 10 μl, SCH 0.1, 1.0, 10 μg (SCH dissolved in 10 μl 5% DMSO intrathecally. Determine the rats’ mechanical withdrawal threshold (MWT before and after giving medication 1, 3, 6, 9, 12, 15, 18, 24 h, and 2 min spontaneous paw withdrawal. Western blot and immuno-fluorescence determine the expression condition of spinal cord dorsal horn of p-ERK, p-p90RSK and Fos protein. Intrathecal injection of SCH772984 has analgesic effects on rats with bone cancer pain, and the effects enhance with increasing dose; intrathecal injection of SCH772984 10 μg could greatly reduce the expression of spinal dorsal horn Fos protein. Injecting walker 256 tumor cells into rats’ tibia could cause behavior changes, such as idiopathic pain sensitivity and pain; the intrathecal tube almost has no effect on motor function of rats; ERK1/2 is involved in bone cancer pain, and intrathecal injection of ERK1/2 specific inhibitors SCH772984 10 μg may effectively relieve bone cancer pain.
Jatana, S K; Dalal, S S; Wilson, C G
.... A study was conducted in our center to study the analgesic effect of administration of oral glucose in various concentrations, in neonates undergoing heel punctures, for collection of blood for investigations...
Full Text Available Introduction: Nowadays, many researches are being conducted in order to evaluate the analgesic effects of different plants which have been used as sedative in traditional medicine. Solanum Melongena is a plant with different theories about its analgesic effects. In this experimental trial research, the effects of intraperitoneal(IP injection of hydro-alcoholic extract of Solanum Melongena were assessed and compared with different doses of morphine and distilled water in Syrian mice. Methods: The effects of different doses of Solanum Melongena (1, 10, 100, and 1000µg/Kg, different doses of morphine sulfate (1, 2, and 4 µg/Kg and distilled water on acute pain was assessed in Syrian mice. Tail flick latency after IP injection was measured for 75 minutes as the index of pain tolerance, using a tail flick apparatus which projects a condensed light stimulus on the animal's tail. Results: Our findings showed that different doses of Solanum increased analgesia index. This effect was more prominent in 45-60 minutes after IP injections which was significantly greater than the control group (p<0.05(. Conclusion: Our findings indicated that the hydro-alcoholic extract of Solanum Melongena produces analgesic effect in a dose- related manner.
This study was designed to evaluate the contribution of caffeine to analgesia in paracetamol-caffeine preparation. Analgesic properties were evaluated in mice using acetic acid-induced writhing and hot plate methods. In the acetic acid method, the test drugs were administered orally to the mice. After 30 min. all the mice ...
Werner, Mads U; Lassen, Birgit Vibeke; Kehlet, Henrik
BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn...... model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn...... and secondary hyperalgesia. RESULTS: The burn injury induced significant increases in erythema (P burn did not differ between dexamethasone and placebo treatments (P >.6). There were no significant...
Jun 1, 2014 ... flavonoids, saponins, tannins steroids and triterpenes. ... produced significant (P < 0.05) and dose-independent anti-inflammatory activity comparable to ... findings are suggestive of the analgesic and anti-inflammatory ...
... and 2-acetamido-5-sulfonamidobenzoic acid (AMSABA, 4) were synthesized and evaluated for their analgesic, antipyretic, anti-inflammatory and cytotoxic activities. HASBA, AASBA and AMASBA showed higher analgesic activity than aspirin (ASA) at 100 mg/kg dose, while AMSABA showed the least analgesic property.
Ide, Soichiro; Kasai, Shinya; Ikeda, Kazutaka
Narcotic analgesics have been widely used for management of severe pain, especially for cancer pain. Most of these drugs are opioids, and they show their analgesic effects by acting through opioid receptors. Significant individual differences in opioid sensitivity can hamper effective pain treatments and increase side effects, which is associated with decreased quality of life. It is thought that genetic factors may affect individual differences in opioid sensitivity. Recent studies using various inbred and knockout mice have revealed that the mu-opioid receptor (MOP) plays a mandatory role in the analgesic properties of opioids. There is also increasing evidence that differences in the sequence of the MOP gene might significantly affect the amount of MOP gene mRNA expression and sensitivity to opioids. Furthermore, it can be thought that individual differences in opioid sensitivity are caused by genetic differences in not only MOP but other biomolecules, such as endogenous opioid peptides, molecules related with metabolic process and second messenger systems. Rapid advances in this research field are leading to a better understanding of relationships between gene polymorphisms and opioid sensitivities, which, in turn, will allow us to more accurately predict opioid sensitivity and opioid requirements in individual patients.
... treated with paracetamol (acetaminophen), aspirin and indomethacin while VII received saline water. Thirty minutes observation period was adhered to. Time related analgesic effect was also investigated. The results showed that the extract contained alkaloids, tannins, saponins, phenols, anthraquinones, and flavonoids.
0.01) activity against all phlogistic agents used in a dose dependent manner. All these effects were compared with reference drug phenylbutazone (100 mg/kg body weight). Keywords: Diospyros cordifolia, analgesic, anti-inflammatory.
This study investigated the analgesic and anti-inflammatory effects of Crinum asiaticum (Amaryllidaceae) leaf ethanolic extract. Analgesic effect was investigated in acetic acid induced writhing model and formalin induced licking model in swiss albino mice. Anti-inflammatory effect was conducted in carrageenan-induced ...
Background: Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice. Methods: Different groups of six ...
Agarwal, Rajat Kumar; Chopra, Gaurav; Agrawal, Atul
Introduction Knee arthroscopy is associated with variable amount of postoperative pain. In an attempt to improve postoperative analgesia, intra-articular injection of local anaesthetic in combination with other agent have been studied. However, the best combination is not known. Aim To compare the analgesic efficacy of intra-articular injection of morphine and dexmedetomidine when added with levobupivacaine in arthroscopic knee surgeries. Materials and Methods Seventy eight patients, scheduled to undergo elective arthroscopic procedure under spinal anaesthesia were recruited for the study. All the patients received 18 ml of 0.25% levobupivacaine however in addition to this Group M patients received 8 mg (2 ml) morphine, Group D patients received 100μg (2 ml) of dexmedetomidine while Group C patients received 2 ml of isotonic saline intra-articularly. Postoperatively the intensity of pain was assessed using Numerical Rating Scale (NRS). Rescue analgesia was given at NRS ≥ 4. The duration of analgesia and total diclofenac consumption was noted. Results The mean duration of analgesia was longest in Group M (576.20±67.09 minutes) followed by Group D (460.93±38.95 minutes) and Group C (370.27±58.80 minutes) statistically this difference was found to be highly significant (p-value < 0.001). Total consumption of diclofenac in 24 hours was found lowest in group M (86.25±27.48 mg) followed by group D (110.87±44.48 mg) and group C (141.35±44.13 mg) this difference was found to be highly significant (p-value < 0.001). Conclusion Morphine when added with levobupivacaine in patients undergoing arthroscopic knee surgery improves the quality and prolongs the duration of postoperative analgesia. PMID:28571238
The last group was given a reference drug, either pentazocine (10 mg/kg) or aspirin (100 mg/kg). The extract at all doses ... 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. In conclusion, the plant ...
Mendes, S S; Bomfim, R R; Jesus, H C R; Alves, P B; Blank, A F; Estevam, C S; Antoniolli, A R; Thomazzi, S M
The aim of the present study is to investigate the antinociceptive, anti-inflammatory, and antioxidant activities of essential oil (EO) of Lippia gracilis Schauer (Verbenaceae) leaves to support the medicinal uses claimed by folklore practitioners in the caatinga region (semi-arid) of Northeastern Brazil. The chemical composition and antinociceptive and anti-inflammatory activities of the EO of Lippia gracilis leaves (50-200 mg/kg) were investigated. Antinociceptive activity of the EO was evaluated by writhing test. Anti-inflammatory activity of the EO was evaluated using paw oedema and peritonitis methods. Oral treatment with the EO of Lippia gracilis leaves elicited inhibitory activity on acetic acid effect at 50, 100, and 200 mg/kg (30.33+/-2.36, 25.20+/-1.48, and 21.00+/-1.54 abdominal writhes, respectively, Pleaves at 200 mg/kg (0.72+/-0.06 mL h, Pleaves at 50, 100, and 200 mg/kg (13.81+/-0.61, 11.77+/-0.91, and 10.30+/-0.60 leukocytes x 10(6)/mL, respectively, Pessential oil allowed the identification of Lippia gracilis as a thymol-p-cymene chemotype (32.68% and 17.82%, respectively). The EO of Lippia gracilis leaves shows antinociceptive and anti-inflammatory activities. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
coated liposomal formulation (PLs) was found to reduce the number of writhing significantly. In some studies, it has been reported that coating of nanoparticles with PS80, which adsorbs apolipoproteins, enables the liposomes to penetrate the BBB . Thus, the analgesic effect of PLs could be due to the presence of. PS80.
Dayan, A D
Methoxyflurane is a volatile, halogenated analgesic, self-administered in a controlled low dose from the Penthrox(®) inhaler for short-term pain relief. It was formerly used in significantly higher doses to produce anaesthesia, when it caused a specific type of dose-related renal tubular damage. The pathogenesis of the renal damage and clinical use of methoxyflurane are discussed here with evidence that a low but effective analgesic dose is not associated with the risk of renal adverse effects. The maximum dose employed to produce analgesia is limited to methoxyflurane 6 mL/day and 15 mL/week, producing a minimum alveolar concentration (MAC) of 0.59 MAC-hours. Renal damage is due to the metabolism of methoxyflurane and release of fluoride ions. Exposure of humans to methoxyflurane ≤2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, has not been associated with renal tubular toxicity. The safety margin of analgesic use of methoxyflurane in the Penthrox ((®)) inhaler is at least 2.7- to 8-fold, based on methoxyflurane MAC-hours or serum fluoride level, with clinical experience suggesting it is higher. It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity. © The Author(s) 2015.
Jun 1, 2014 ... drugs (NSAIDS) and opioids are used in management of mild to moderate and severe pains respectively. These drugs have serious limitation due to their side effects such as gastrointestinal irritation, tolerance and dependency (Howland and Mycek, 2006). Medicinal plants have been found to be useful.
Islam, M.R; Mannan, M.A; Kabir, M.H.B; Islam, A; K.J. Olival
The present study was carried out to investigate the analgesic, anti-inflammatory, antibacterial and antifungal properties of ethanol leave extract of Mangifera indica. For evaluation of analgesic and anti-inflammatory properties, acetic acid induced writhing response model and carrageenan induced paw edema model were used in Swiss albino mice and Wistar albino rats, respectively. In both cases, leaves extract were administered and the obtained effects were compared with commercially availabl...
Jones, Carissa P; Carver, Scott; Kendall, Lon V
Tail biopsy in mice is a common procedure in genetically modified mouse colonies. We evaluated the anesthetic and analgesic effects of various agents commonly used to mitigate pain after tail biopsy. We used a hot-water immersion assay to evaluate the analgesic effects of isoflurane, ice-cold ethanol, ethyl chloride, buprenorphine, and 2-point local nerve blocks before studying their effects on mice receiving tail biopsies. Mice treated with ethyl chloride spray, isoflurane and buprenorphine, and 2-point local nerve blocks demonstrated increased tail-flick latency compared with that of untreated mice. When we evaluated the behavior of adult and preweanling mice after tail biopsy, untreated mice demonstrated behavioral changes immediately after tail biopsy that lasted 30 to 60 min before returning to normal. The use of isoflurane, isoflurane and buprenorphine, buprenorphine, 2-point nerve block, or ethyl chloride spray in adult mice did not significantly improve their behavioral response to tail biopsy. Similarly, the use of buprenorphine and ethyl chloride spray in preweanling mice did not improve their behavioral response to tail biopsy compared with that of the untreated group. However, immersion in bupivacaine for 30 s after tail biopsy decreased tail grooming behavior during the first 30 min after tail biopsy. The anesthetic and analgesic regimens tested provide little benefit in adult and preweanling mice. Given that tail biopsy results in pain that lasts 30 to 60 min, investigators should carefully consider the appropriate anesthetic or analgesic regimen to incorporate into tail-biopsy procedures for mice. PMID:23294888
Five dogs each were randomly treated with 30mg/kg paracetamol (treatment KXDTA) intravenously or equal volume of normal saline (treatment KXDTS) to evaluate if paracetamol potentiate the analgesic effects of tramadol during the intra-operative period. Thirty minutes later, both groups were treated with 3mg/kg tramadol ...
Vekariya, Shweta; Nishteswar, K; Patel, Bhupesh R; Nariya, Mukesh
Mahanimba (Melia azedarach Linn.) is a deciduous tree of family Meliaceae and its root is mainly used in painful condition such as Gridhrasi (sciatica) in Ayurveda. Ethnomedicinal claims indicate that its leaves are used to treat fever, but its medicinal activities have not been proven by research. This study was aimed to evaluate the potential analgesic and antipyretic activities of M. azedarach L. leaf powder (MLP) and M. azedarach L. root powder (MRP). The root and leaves of M. azedarach were made into powder using guidelines mentioned in the Ayurvedic Pharmacopoeia of India. The analgesic activity of the test drugs was evaluated against acetic acid-induced writhing test in mice and radiant heat-induced pain in albino rats, and antipyretic activity was evaluated against Brewer's yeast-induced pyrexia using Charles Foster rats. In acetic acid induced writhing in mice, the test drugs MRP (1.3mg/kg) exhibit insignificant reduction in writhing reflex while MLP (1.3mg/kg) did not show any significant effect in comparison to the control group. MRP showed mild-to-moderate insignificant increase in latency of withdrawal response at 60 (26.74%) and 120 min (27.25%), while MLP did not show central analgesic effect in radiant heat model in rats. MRP showed a significant reduction in rectal temperature after 3 and 6 h, while MLP-treated group showed significant reduction after 6 h. MRP has mild-to-moderate peripheral and central analgesic effects, while MLP has not shown significant analgesic effects in both the experimental models. MRP has more pronounced antipyretic effect compared to MLP.
Mina Kamkar Asl
Full Text Available Objective: The beneficial effects of clove on toothache have been well documented. We have also previously shown the analgesic effects of clove essential oil. The present work was done to investigate the analgesic effects of the aqueous extract of clove using hot plate test. The possible role of opioid receptors in the analgesic effects of clove was also investigated using naloxone. Materials and Methods: Ninety male mice were divided into nine groups: (1 Saline, (2-4 Aaqueous (Aq 50, Aq 100, and Aq 200 groups which were treated with 50, 100, and 200 mg/kg of aqueous extract of clove, respectively, (5-7 Ethanolic (Eth 50, Eth 100, and Eth 200 groups which were treated with 50, 100, and 200 mg/kg of ethanolic extract of clove, respectively, and (8-9 Aq 100- Naloxone and Aq 200- Naloxone which were pretreated with 4 mg/kg of naloxone before injection of 100 or 200 mg/kg of the aqueous extract. The hot plate test was performed as a base record 10 min before injection of drugs and consequently repeated every 10 minutes after the injection. Results: The maximal percent effect (MPE in the animal groups treated with 50, 100, and 200 mg/kg of aqueous extract was significantly higher than the control group. Pretreatment with naloxone reduced the analgesic effects of both 100 and 200 mg/kg of the aqueous extract. Administration of all three doses of the ethanloic extract also non-significantly increased the MPE. Conclusion: The results of the present study showed that aqueous extract of clove has analgesic effect in mice demonstrated by hot plate test which is reversible by naloxone. The role of opioid system in the analgesic effect of clove might be suggested. However, more investigations are needed to elucidate the exact mechanism(s.
Andersen, Lars Peter Holst
The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of
Vasconcelos, M A Lemos; Ferreira, D da Silva; Andrade e Silva, M L; Veneziani, R Cassio Sola; Cunha, W R
The present study describes the analgesic effects of the crude extracts (hexane, methylene chloride and ethanol) obtained from the aerial parts of Miconia albicans (Melastomataceae) using the writhing test and the hot plate models for pain in mice. The extracts in hexane and methylene chloride, given orally, produced significant antinociception in the writhing test. On the other hand, none of the extracts had a significant effect on the hot plate test, a fact suggesting that the substances present in the extracts may rather have peripheral analgesic activity.
Phytochemical screening was carried out on the ethylacetate portion of the ethanolic extract of the leaves of Pseudocedrella kotschyii and then evaluated for its analgesic (acetic acid-induced writhing) and anti-inflammatory (raw egg albumin-induced oedema) activities in mice and rats respectively. Phytochemical screening ...
Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V
The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.
Suzana Guimarães Leitão
Full Text Available Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols, triterpene acids from ursane and oleanane types, iridoids (free and glucosides, as well as simple phenols.
Full Text Available Background: Opioid drugs are the most effective drugs for the treatment of moderate to severe pain. Rates of opioid use are influenced by a variety of factors. The aim of this study was to determine the pattern of use of parenteral opioid drugs in hospitalized patients in a referral teaching hospital. Methods: In a retrospective study, required data were extracted from medical records of adult patients who had received any parenteral opioid analgesic in the 6-month period from March 2013 to September 2013. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD system method was used for evaluation of opioid analgesic use in patients.Results: The overall usage of parenteral opioid analgesics was 730.51 DDDs with meperidine (Pethidine having the most amounts of use (588.69 DDDs and 33.23 DDDs/100 bed-days. Overall, the male surgery ward and emergency department had the most amounts of use based on the number of DDDs (445.8 DDDs and per 100 bed-days (1046 DDDs/100 bed-days, respectively. Methadone use was most in the infectious diseases ward.Conclusion: The trend of parenteral opioid analgesics consumption is increasing in this hospital. Therefore, better adherence to pain treatment guidelines by medical staff is necessary for rational use of these drugs.
Roldão, Erika de Freitas; Witaicenis, Aline; Seito, Leonardo Noboru; Hiruma-Lima, Clélia Akiko; Di Stasi, Luiz Claudio
Cordia verbenacea is a medicinal plant popularly used in Brazil as anti-inflammatory, antiulcer and anti-rheumatic agent without detailed pharmacological and toxicological studies. The study was aimed to investigate the effects of Cordia verbenacea in antiulcer, analgesic and antioxidant assays, as well as to evaluate its toxic effects and phytochemical profile. Antiulcer activity of plant extract was evaluated using ethanol/HCl, ethanol and piroxican-induced gastric lesions methods. The pH, volume and total acid of gastric juice were determined by pylorus-ligated assay. Analgesic activity was evaluated by writhing, tail-flick and hot-plate tests. Antioxidant activity was determined by in vitro lipoperoxidation assay. Acute toxicity and number of deaths were evaluated by Hippocratic screening. The ethanol leaf extract shows a potent antiulcer activity in the ethanol/HCl and absolute ethanol-induced gastric lesions. The IC(50) value of plant extract on the lipid peroxidation was 76.11mug/ml. Preliminary phytochemical tests were positive for flavonoids, steroids, saponins, fixed acids, alkaloids and phenols. In the analgesic models the extract did not present any activity. Cordial verbenaceae showed a potent antiulcer activity at the dose of 125mg/kg and this effect may be associated with an improvement in stomach antioxidant mechanisms.
Objective. Clinical studies have suggested that gabapentin may produce analgesia in postoperative patients. The aim of this study was to investigate the analgesic effects of low-dose gabapentin administered during the first 24 hours after abdominal hysterectomy. Methods. A prospective, double-blind, randomised study ...
The aim of this research is to investigate the analgesic, haematologic and some physiological effects of extradural bupivacaine on dogs using six clinically healthy adult male dogs. The method used is by obtaining baseline data for physiological variables from each dogs using the multiparameter patient monitors (GD3, ...
induced paw edema method and cotton pellet granuloma test. B. coriacea at 50mg/kg, 100mg/kg and 200mg/kg demonstrated significant (P<0.05) analgesic effect by increasing hot plate latency period. This increase in hot plate latency was ...
Results: The values of total number of Writhing Reflex (WRT) and Writhing reflex per minute(WR/min) were found to be significantly higher in Group C compared with Groups SD and TD (P = 0.009). Conclusion: Single and repeated doses of diclofenac sodium via epidural route have an analgesic effect in a visceral pain ...
Ainul Atiqah binti Hilmi
Full Text Available Background: Pain is a feeling stimulated by the nervous system which can be suppressed by giving an analgesic agent. Some studies revealed that pineapples have an analgesic effect. This study aim was to determine analgesic effect of pineapple on mice. Methods: In this experimental study, the effect was examined by using a writhing method on the 28 male mice. Subjects were divided into 4 groups with 7 mice each. The control group received aquades and other groups received pineapple fruit juice with 20%, 40% and 80% concentration with the dosage of 10 mL/kg/body weight. After 30 minutes, 3% acetic acid was injected intraperitoneally to induce pain. Writhing responseswere observed every 5 minutes for 30 minutes. Results: The result for mean of total writhing reaction was 2.39±0.40, 1.92±0.40, 1.50±2.13, 1.66±0.11 respectively for group 1 to 4. These data indicated a significant decrease of total writhing response in mice with 20%, 40% and 80% concentration compared to control group (p=0.023;p=0.000 and p=0.000 respectively. Most optimal concentration was40% with the protective percentage equal to 71.8%. Conclusion: Pineapple fruit juice concentrations (20%, 40%, and 80%has an analgesic effect with the most optimal concentration of 40%.
Apr 24, 2013 ... Choi E, Kwang J (2004). Anti-inflammatory, analgesic and anti-oxidant activities of the fruits of Foeniculum vulgare. Fitoterapia 75:557-565. Choi J, Jung HJ, Lee KT, Park HJ (2005). Antinociceptive and anti- inflammatory effects of saponins and sapogenins obtained from the stem of Akebia quinata. J. Med.
Full Text Available Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR, as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53. Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.
Non-opioid type of analgesics was utilized more than opioid. With oral route being the most favoured route of administration and opioids with exception of tramadol were exclusively administered parenterally. Paracetamol was the commonest prescribed analgesic in accident and emergency department. The result of this ...
F. Struyf; J. Nijs; M. Meeys; D. Meuffels; J. de Vries; Dr. L.P. Voogt
BACKGROUND: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic
Rodent models were employed in screening the analgesic effect of the extract. Pain indices evaluated in hot plate and tail flick tests, formalin pain test and mouse writhing assay were mean reaction time to latent heat, time spent in licking of injected paw and abdominal writhes, respectively. Results: Oral administration of the ...
The purpose of this study was to evaluate the extract for antipyretic and analgesic activity, and determine its probable mechanism of action. Methods: Pyrexia was induced in rabbits by ... The extract (250, 500 mg/kg) and aspirin produced comparable antipyretic effects up to 60 min. The extract did not inhibit the growth of the ...
Branthwaite, A; Cooper, P
The effect of branding--that is, the labelling and marketing--of a well-known proprietary analgesic used to treat headaches was studied in a sample of women given a branded or unbranded form with either an inert or an active formulation. The sample was also divided according to whether the subjects were regular users of the brand or users of other brands. The findings showed that branded tablets were overall significantly more effective than unbranded tablets in relieving headaches. Differential effects were observed: the effects of branding were more noticeable one hour after the tablets were taken compared with 30 minutes; in the women given the placebo; and in the users of the brand compared with the users of other brands. It is hypothesised that these effects are due to increased confidence in obtaining relief with a well-known brand, and that branding has an analgesic effect that interacts with the analgesic effects of placebos and active ingredients. PMID:6786566
Tian, Zhen; Wang, Dong-sheng; Wang, Xin-shang; Tian, Jiao; Han, Jing; Guo, Yan-yan; Feng, Bin; Zhang, Nan; Zhao, Ming-gao; Liu, Shui-bing
Our previous studies have demonstrated the critical roles of calcium-stimulated adenylyl cyclase 1 (AC1) in the central nervous system in chronic pain. In the present study, we examined the analgesic effects of NB001, a selective inhibitor of AC1, on animal models of ankle joint arthritis and knee joint arthritis induced by complete Freund’s adjuvant injection. NB001 treatment had no effect on joint edema, stiffness, and joint destruction. Furthermore, the treatment failed to attenuate the di...
Günther, Thomas; Dasgupta, Pooja; Mann, Anika; Miess, Elke; Kliewer, Andrea; Fritzwanker, Sebastian; Steinborn, Ralph; Schulz, Stefan
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant κ receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to μ, κ and δ receptors. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of particular multi-opioid receptor ligands, but not on their medicinal chemistry and design. © 2017 The British Pharmacological Society.
Højsted, Jette; Kurita, Geana Paula; Kendall, Sally
Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain...... patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient...
Højsted, Jette; Kurita, Geana Paula; Kendall, Sally
cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain......Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient...
Højsted, Jette; Kurita, Geana Paula; Kendall, Sally
Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...
Anti-inflammatory and analgesic effects of Careya arborea stem bark in experimental animal models. ... The extract also inhibited peritoneal leukocyte migration in mice. The MECA also produced significant (p < 0.01) analgesic activity in both models. Keywords: Careya arborea, anti-inflammatory, analgesic, rat, mice
Karaman, Semra; Kocabaş, Seden; Zincircioğlu, Ciler; Firat, Vicdan
The aim of this study was to determine if preemptive use of the NMDA receptor antogonist ketamine decreases postoperative pain in patients undergoing abdominal hystrectomy. A total of 60 patients admitted for total abdominal hysterectomy were included in this study after the approval of the ethic committee, and the patients were randomly classified into three groups. After standart general anaesthesia, before or after incision patients received bolus saline or ketamine. Group S received only saline while Group Kpre received ketamine 0.4 mg/kg before incision and saline after incision, and Group Kpost received saline before incision and 0.4 mg/kg ketamine after incision. Postoperatif analgesia was maintained with i.v. PCA morphine. Pain scores were assessed with Vizüal Analog Scale (VAS), Verbal Rating Scale (VRS) at 1., 2, 3., 4., 8., 12. ve 24. hours postoperatively. First analgesic requirement time, morphine consumption and side effects were recorded. There were no significant differences between groups with respect to VAS / VRS scores, the time for first analgesic dose, and morphine consumption ( p>0.05). Patients in Group S had significantly lower sedation scores than either of the ketamine treated groups ( pketamin had no preemptive analgesic effect in patients undergoing abdominal hysterectomy, but further investigation is needed for different operation types and dose regimens.
Berna, C; Cojan, Y; Vuilleumier, P; Desmeules, J
Over the past twenty years, neuroscience has changed our understanding of placebo analgesia. Often perceived by researchers as a response bias adding noise to the assessment of efficacy, in the patients' view, it is associated with charlatanism. The origin of the word, qualifying a patient's response to "please" the doctor, did not help its rightful appreciation. However, today the placebo analgesia is considered as a psychobiological phenomenon. Thanks to pharmacological manipulations and the development of functional brain imaging, the neural circuitry involved in this effect as well as the role of endorphins and dopamine have been identified. This article describes our current knowledge about this fascinating phenomenon: a psychological modulation can lead to a biological effect.
"Ghazi Saidi K
Full Text Available In a randomized, double blind study , we compared post operative pain and analgesic requirement in patients undergoing cesarean section with two types of general anesthesia: standardized general anesthesia (control group=26 cases and preemptive low-dose ketamine (0.2 mg/kg administered prior to anesthesia induction (keratmine group=27 cases. Postoperative analgesia was provided for both groups using morphine intravenously based on visual analogue scale (VAS. After the operation we found that the time from the end of surgery to the first request for analgesic was longer in ketamine group (10.22±8 hrs than in the control group (1.65±1.01 hrs0 (P<0.001 Mean dose of morphine consumption over 24 hrs was less in the ketamine group (625±3.45 mg than in the control group (17.73±4.08 mg (P<0.001 VAS of pain scores were lower in ketamine group during 24 hr (P<0.001. APGAR Scores were similar between the groups. No patient in either group had postoperative hallucination. In conclusion, ketamine in low dose has a preemptive analgesia effect that reduces central sensitization in cesarean section and reduces postoperative analgesic requirement.
Full Text Available This study was performed to evaluate the analgesic activity and the toxicity of ketorolac in normal and fractionated (1.5 Gy/day/4 days γ-irradiated animals. Determination of brain serotonin content and serum prostaglandin level were also undertaken. The analgesic activity was tested using formalin test, at three dose levels (15, 30 and 60 mg/kg after 1 and 7 days post radiation exposure. LD50 determinations and assessment of liver and kidney function tests were performed. Our results indicated marked analgesic effects on the early and late phases of nociception. Double treatment with ketorolac and irradiation increased brain serotonin content. The acute LD50 of ketorolac was decreased in irradiated animals as compared to the LD50 of normal animals. Double treatment with ketorolac and irradiation induced an elevation of gastric mucin content, urea and BUN levels on the 1st day post irradiation, whereas, albumin level was lowered and globulin level was elevated after 7 days post irradiation. Depending on this study the dose of ketorolac used for treating cancer patients addressed to radiotherapy should be reduced, however, this requires further clinical confirmation.
Nastase, Anca; Ioan, Silvia; Braga, Radu I
Nicotine (from cigarette smoke) and caffeine (from coffee) have analgesic effects in humans and experimental animals. We investigated the combined effects of coffee drinking and cigarette smoking on pain experience in a group of moderate nicotine-dependent, coffee drinking, young smokers. Pain...... threshold and pain tolerance were measured during cold pressor test following the habitual nocturnal deprivation of smoking and coffee drinking. Smoking increased pain threshold and pain tolerance in both men and women. Coffee drinking, at a dose that had no independent effect, doubled the increase in pain...
Wang, Yuan; Liu, Xin; Wang, Dan; Yang, Junxian; Zhao, Long; Yu, Jing; Wang, Rui
Endomorphins are endogenous opioid peptides in mammals and display a strong antinociceptive effect after central administration. However, the clinical usage of these peptides is limited because of their diminished analgesic effect following systemic injection and their inability to cross the blood-brain barrier. In this study, we characterized the in vivo effects of four novel endomorphin-1 analogues (termed MELs), which previously showed potential as highly potent analgesics with a good pharmacological profile in vitro. The analogues were administered intravenously to several rodent pain models to examine their antinociception and blood-brain barrier permeability. The tested peptides, especially MEL1214, showed good analgesic activity and blood-brain barrier permeability. Behavioral studies showed dose-dependent analgesic effect after systematic administration of MEL1214 in the tested pain models. Pre-treatment of subcutaneous administration of naloxone methiodide did not affect the antinociception of these peptides. As compared to morphine, MEL1214 was less prone to induce tolerance after consecutive intravenous administration for 5 days. Gastrointestinal transit was evaluated by the isolated colon response and bead expulsion to determine the potential constipation effect. In contrast to morphine, MEL1214 produced no significant constipation effect at an equivalent dose. MEL1214 shows promise as a suitable compound to treat pain with reduced side effects, and exhibits good potential to be further developed as a novel opioid analgesic in pain treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
Dong Wook Lim
Full Text Available Indian gooseberry (Emblica officinalis fruit, also known as “Amla” is one of the oldest edible fruits known in India. It has also traditionally been used to treat inflammation, and as an analgesic to treat wounds. However, experimental evidence for the analgesic effects of E. officinalis has been lacking. The present study investigated whether E. officinalis extracts exhibit analgesic effects in the plantar incision (PI and spared nerve injury (SNI pain-model rats. We evaluated the mechanical withdrawal threshold (MWT using von Frey filaments, and pain-related behavior was determined after surgery based on ultrasonic vocalization (USV. The group treated with E. officinalis extracts at 300 mg/kg had significantly increased MWT values at 6 h and 24 h after the PI, and had a significantly reduced number of 22–27-kHz USVs at 6 h and 24 h after PI. Moreover, after 15 days of continuous treatment with E. officinalis extracts, the treated group showed significantly alleviated SNI-induced hypersensitivity and reduced pro-inflammatory cytokine levels. Thus, E. officinalis extracts have potential analgesic effects in both postoperative and neuropathic pain models in vivo.
Sivakumar, T; Perumal, P; Kumar, R Sambath; Vamsi, M L M; Gomathi, P; Mazumder, U K; Gupta, M
Analgesic, antipyretic activity and toxicity study of the leaves of Bryonia laciniosa Linn. (Family: Cucurbitaceae) was evaluated in the standard animal models. The methanol extract of Bryonia laciniosa (MEBL) was evaluated by hot plate and acetic acid-induced writhing methods to assess analgesic activity. The antipyretic activity of the extract was also evaluated by normal body temperature and yeast-induced hyperpyrexia. The extract showed significant analgesic and antipyretic activity. The MEBL was further evaluated for toxicity at the doses of 125 and 250 mg/kg administered orally for 14 days in rats. At the end of experiments, the blood, liver function and kidney metabolism were observed. The hematological profile and different biochemical parameters such as SGOT, SGPT and ALP were estimated. The present study revealed that MEBL exhibited significant analgesic and antipyretic activity in the tested experimental animal models. The toxicity study indicates that the extract is not toxic at the tested doses.
Materials and Methods: The analgesic and anti-inflammatory activities of PYS were determined using acetic acid-induced writhing response, hot plate test, xylene-induced ear swelling test, carrageenan-induced paw edema test, and acetic acid-induced capillary permeability and leukocyte infiltration test with oral doses of ...
Full Text Available Background and Aims: Perioperative beta blockers are also being advocated for modulation of acute pain and reduction of intraoperative anesthetic requirements. This study evaluated the effect of perioperative use of esmolol, an ultra short acting beta blocker, on anesthesia and modulation of post operative pain in patients of laproscopic cholecystectomy. Material and Methods: Sixty adult ASA I & II grade patients of either sex, scheduled for laparoscopic cholecystectomy under general anesthesia, were enrolled in the study. The patients were randomly allocated to one of the two groups E or C according to computer generated numbers. Group E- Patients who received loading dose of injection esmolol 0.5 mg/kg in 30 ml isotonic saline, before induction of anesthesia, followed by an IV infusion of esmolol 0.05 μg/kg/min till the completion of surgery and Group C- Patients who received 30 ml of isotonic saline as loading dose and continuous infusion of isotonic saline at the same rate as the esmolol group till the completion of surgery. Results: The baseline MAP at 0 minute was almost similar in both the groups. At 8th minute (time of intubation, MAP increased significantly in group C as compared to group E and remained higher than group E till the end of procedure. Intraoperatively, 16.67% of patients in group C showed somatic signs as compared to none in group E. The difference was statistically significant. 73.33% of patients in group C required additional doses of Inj.Fentanyl as compared to 6.67% in group E. Conclusions: We conclude that intravenous esmolol influences the analgesic requirements both intraoperatively as well as postoperatively by modulation of the sympathetic component of the pain i.e. heart rate and blood pressure.
Srinivasa, U; Rao, J Venkateshwara; Krupanidhi, A M; Shanmukhappa, S
The analgesic activity of ethanolic extract of Justicia beddome leaves (Family: Acanthaceae) was evaluated in albino rats using Eddy's hot plate method. The extract at 50 and 100 mg/ kg, (i.p), showed significant analgesic activity at 90 minutes of administration. The analgesic effect of the extract was comparable to that of morphine sulphate.
Hoek, Amber E; De Ridder, Maria A J; Bayliss, Antonia; Patka, Peter; Rood, Pleunie P M
Pain is a common presenting complaint of emergency department patients. Providing instructions that can be easily recalled by patients is an important step in enabling patients to manage their pain following discharge. The effect of the introduction of written discharge instructions for pain medication on patients' recall of instructions was evaluated in this study. A patient-control study within a prospective follow-up study was performed. In the first phase, no written discharge instructions were available. Patients discharged on analgesics filled in a digital questionnaire regarding correct analgesics use. In the second phase, patients were discharged with additional written instructions and completed the same questionnaire. In the first phase, 40% of patients correctly recalled instructions for taking analgesics. In the second phase, significantly more patients, 71% (Pwritten instructions about the appropriate use of analgesics, and that emergency departments that are not yet doing this should consider introducing this policy. It is a relatively low-cost measure that could lead to a significant improvement in quality of care.
Full Text Available The present study aims to investigate the analgesic activity of the methanol extract of the galls of Quercus infectoria in rats using hot plate and tail-flick methods. The extract was administered intraperitoneally at a dose of 20 mg/kg while morphine sulfate and sodium salicylate (10 mg/kg served as standards. The methanol extract exhibited significant analgesic activity in the tail-flick model (P<0.05 by increasing the reaction time of the rats to 8.0 sec at 30 min after treatment in comparison to control (4.4 sec. Morphine sulfate produced a reaction time of 11.9 sec in the same test. At the peak of activity (30 min, the extract produced maximum possible analgesia (MPA of 34.2%, whilst morphine sulfate achieved a peak MPA of 70.9%. No analgesic effects have been observed using sodium salicylate in the tail-flick model. In the same model, the extract and sodium salicylate demonstrated comparable reaction times. Tail-flick is a better method to evaluate analgesic activity as no significant results were observed for all treatments using hot plate with the exception of morphine sulfate, which showed significant results only at 45 and 60 min after treatment. In conclusion, the methanol extract of the galls of Quercus infectoria displayed analgesic activity.
SHazad Daroogari; Rahmatollah Parandin; Namdar Yousofvand; Daryoush Shakibaie
Background & objectives: Syzygium aromaticum (Clove) is a medicinal plant usually used in traditional medicine to reduce toothache. The aim of the present study was to evaluate the analgesic effect of topical Clove oil on acute and chronic pain in male mice using formalin test. Methods: In this study, 24 mice were divided into 4 groups: control, morphine (as positive control), Clove oil, and Clove oil plus morphine groups. Before the formalin test, the animals were treated topically with c...
Full Text Available AIM OF THE STUDY To evaluate whether Gabapentin when given orally preoperatively at a dose of 300 mg has an effect on postoperative pain and analgesic requirement in patients undergoing total abdominal hysterectomy under spinal anaesthesia. The study also evaluates the side effects associated with administration of Gabapentin. METHODOLOGY This is a prospective, randomised, single blinded case controlled study. This study was conducted in total of 60 patients who underwent elective abdominal hysterectomy in our institute over a period of four months. Patients were randomly allocated into two groups: Group G (Gabapentin Group and Group P (Placebo Group. Patients in Group G received Gabapentin 300 mg orally and Group P patients received placebo capsules with sips of water two hours before surgery. Time since spinal anaesthesia to first requirement of analgesic (T, total analgesic requirement in first 24 hours, visual analogue scale (VAS scores at rest and movement, Ramsay sedation score, side effects of the drug like somnolence, dizziness, confusion, nausea, vomiting were recorded in first 24 hours postoperatively. RESULT Single oral dose of Gabapentin 300 mg when given preoperatively reduces the postoperative pain scores and total tramadol consumption in patients undergoing abdominal hysterectomy under spinal anaesthesia. Sedation was the only significant side effect observed with the Gabapentin usage. Thus, Gabapentin can be considered as an adjunct in treating postoperative pain. CONCLUSION Oral Gabapentin 300 mg given preoperatively as preemptive analgesic is effective in total abdominal hysterectomy patients under spinal anaesthesia without any significant complications.
Ezeja, MI; Omeh, YS; Ezeigbo, II; Ekechukwu, A
Background: Dialium guineense is a medicinal plant used by some communities of Enugu-Ezike in Enugu State, Nigeria for treatment of fever, headache and other diverse ailments. Objectives: The present study evaluated the analgesic activity of the methanolic stem bark extract of the plant. Method: Acetic acid-induced abdominal constriction or writhing, tail immersion and hot plate analgesic models in albino Wistar mice were used for the study. Three test doses (250, 500, 1000 mg/kg body weight)...
Chen, Shu-Shu; Liu, Ling; Hu, Pin; Shi, Bi-Zhen; Fu, Yi-Kang; Luo, Rui; Xie, Cai
To study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation. Thirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age. The respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (Pcontrol group (Pcontrol groups (P>0.05). Fentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.
Camu, Frederic; Vanlersberghe, Caroline
Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.
Reshma R Parekar
Full Text Available Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g and Swiss albino mice (20-25 g of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice, Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey′s test and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01 less number of writhes. It showed significant (P < 0.001 anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001 and decrease in granuloma weight (P < 0.05 as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001. Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.
Wang, Xiao-ping; Wang, Zhong-gui; Wang, Xiao-ting; Ye, Rong
To compare the effects of analgesic therapies on odontalgia caused by pulpitis in molars by three different methods. 173 molars were diagnosed as irreversible pulpitis, and randomized block designed in three groups. Under block or local anesthesia: 46 cases of the first group, leaving teeth on open drainage, after 1 day, sealing devitalized material (arsenic), arranged next appointment 2 weeks later. 52 molars of the second group, enlarging exposure site, drainage several minutes only, sealed devitalized material, re-examined 2 weeks later. 75 cases of the third group, removing roof of pulp chamber, undergoing pulpectomy directly, re-examined 1 week later. Adopting VAS(vital analogue scale) to analyze the pulp receptivity of three different methods and to evaluate the analgesic effects by complete analgesia, effective analgesia, and no response. The data was analysed using chi-square test. The rate of complete analgesia was 50.0%, 63.46% and 76.0%, respectively. There was a significant difference in complete analgesia among the three methods. The analgesic effect of the third group (pulpectomy) was significantly higher than that of the first group (PPulpectomy group had impossibility of adverse effects caused by using devitalizing material (arsenic). It is worthy to adopt pulpectomy extensively to relieve the pain of molars caused by pulpitis clinically. The course of treatment of the third group was significantly shorter than other groups, and the simultaneous symptoms occurred rarely.
Roseane Leandra da Rosa
Full Text Available Luehea divaricata (Malvaceae is a plant widely used for treatment of various inflammatory and infectious conditions; however few reports discuss its biological properties. The aim of this study was to evaluate the anti-inflammatory and analgesic effects as well as the macrophage activity in mice treated with the hydroalcoholic crude extract of L. divaricata(CLD. Thin layer chromatography revealed presence of epicathequin, stigmasterol, lupeol and α,β-amyrin in the extract. To evaluate the anti-inflammatory and analgesic activities, animals were subjected to paw edema induced by carrageenan test, writhing, formalin and capsaicin tests. Immunomodulatory activity was evaluated by adhesion and phagocytic capacity, lysosomal volume, and reactive oxygen species (ROS production by peritoneal macrophages, after daily treatment with CLD for 15 days. CLD promoted reduction in paw edema (36.8% and 50.2%; p<0.05 at doses of 100 and 300 mg/kg, respectively, inhibited writhing behavior at the higher dose (64.4%, p<0.05, reduced formalin reactivity (81.2% and 91.6% at doses of 100 and 300 mg/kg, respectively, p<0.05, and reduced capsaicin reactivity by 63.9% (300 mg/kg. CLD (200 mg• kg-1• day-1 increased phagocytosis capacity of macrophages (~3 fold, p<0.05, neutral red uptake (~50%, p<0.001, and ROS production (~90%, p<0.001. These data suggest that CLD possesses anti-inflammatory, analgesic and immunostimulatory properties.
Abdalla S. Elhwuegi
Full Text Available Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.
Full Text Available To compare the analgesic effectiveness of the prophylactic therapy and continued therapy with naproxen sodium after a simple dental extraction. Material and methods: This prospective randomized, parallel, single-blind clinical trial was developed in the Dental Clinic of the Universidad Alas Peruanas in Trujillo (Peru. The patients, who required simple extraction due to dental caries, were randomly distributed into three groups: 30 of them took 550mg naproxen sodium in the preoperative period and then every 12 hours, other 30 took 550mg naproxen sodium in the postoperative period and then every 12 hours, and 30(control group, received 400mg ibuprofen in the postoperative period and then every 8 hours, depending on the established criteria. The procedure was standardized, analgesic effectiveness was assessed by visual analog scale and the presence of adverse drug reactions was evaluated as well. Data were analyzed using ANOVA and Duncan’s test using IBM SPSS 22 with a significance level of 5%. Results: Continued therapy with naproxen sodium showed greater analgesic effectiveness after a simple extraction at 1, 8 and 24 hours (p<0.005. Conclusion: Continued therapy with naproxen sodium presented greater effectiveness than prophylactic therapy with naproxen sodium after a simple extraction.
Pedersen, J L; Galle, T S; Kehlet, H
BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers...... on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo...... hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P ketamine treatment compared with placebo immediately after injection (P
Full Text Available Objective: To determine the phytochemical screening, antioxidant activity and analgesic effect of crude ethanol extract of Waltheria ovata (W. ovata Cav. root in mice. Methods: Phytochemical screening was developed by color or the precipitate formation. The evaluation of antioxidant activity and total phenolic content were assessed using 2,2- diphenyl-1-picrylhydrazyl and Folin-Ciocalteu’s reagent, respectively. The analgesic effect was determined by acetic acid and formalin test. Different doses of W. ovata (50, 150, 300 and 500 mg/kg body weight were administered p.o. to various groups of mice. Results: Phytochemical screening confirmed the presence of phenolic compounds, flavonoids, tannins, saponins, terpenoids and steroids. The antioxidant activity showed 25% for 0.1 µg/ mL and was significantly higher (P < 0.01 than trolox and vitamin C, meanwhile, the total phenolic content (gallic acid equivalent was 2 200 mg/g of dry extract. W. ovata demonstrated an independent analgesic effect in different experimental models, like, acetic acid (72.51%, P < 0.01 and formalin (first phase: 58.6%, P < 0.01; second phase: 91.5%, P < 0.01, respectively at dose of 300 mg/kg, similar to diclofenac (5 mg/kg and morphine (30 mg/kg, respectively. Conclusions: W. ovata root’s crude ethanol extract showed strong antioxidant activity and high phenolic content. The analgesic effect was demonstrated in two experimental models of pain implying that both peripheral and central mechanisms were involved. This might be due to the presence of various phytochemicals in the extract.
Ayşe Çiğdem Tütüncü
Full Text Available Aim: The aim of this study was to evaluate the analgesic efficacy and side-effects of dexketoprofen and tramadol administered intravenously before thyroid surgery. Methods: A group of 63 patients, who were graded as American Society of Anaesthesiologists physical status (ASA I-II and in whom a thyroid surgery was planned, were randomly divided into 3 groups: the patients in Group D (n=21, Group T (n=21 and Group K (n=21 received 50 mg (2ml of dexketoprofen, 100 mg (2 ml of tramadol and 2 ml 0.9% NaCl serum, respectively, before surgery. Standard anesthesia monitoring, induction and maintenance was performed in all patients. At the end of the surgery, the incision line was infiltrated with bupivacaine in all patients. Visual analogue scale (VAS scores (0: no pain,10: worst pain ever were recorded in all groups at the beginning (in the recovery room, at the 1st, 6th, 12th and 24th hour post-operatively. Nausea-vomiting, head and neck pain, sore throat, dizziness and other possible side-effects were also asked and recorded. Results: VAS scores were statistically higher in Group K than in Group T and Group D at the 1st, 6th, 12th, and 24th hours postoperatively. There was no significant difference between Group T and Group D in VAS scores evaluated at all time points.. The fentanyl consumption in Group K was higher than in the other two groups. The incidence of headache, sore throat nausea, vomiting was higher in Group K compared with that in Group T and Group D. Conclusion: We determined that preoperative tramadol and dexketoprofen had similar analgesic effect and dexketoprofen caused less side-effects. (The Medical Bulletin of Haseki 2014; 52: 5-9
Full Text Available Background: Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. Objectives: The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. Animals and Methods: The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Statistical Analysis: Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Results and Conclusion: Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.
Kristensen, David Møbjerg; Mazaud-Guittot, Sverine; Gaudriault, Pierre
policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have......Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental...
Jergova, Stanislava; Gajavelli, Shyam; Varghese, Mathew S; Shekane, Paul; Sagen, Jacqueline
Chronic neuropathic pain represents a clinically challenging state with a poor response to current treatment options. Long-term management of chronic pain is often associated with the development of tolerance, addiction, and other side effects, reducing the therapeutic value of treatment. Alternative strategies based on cell therapy and gene manipulation, balancing the inhibitory and excitatory events in the spinal cord, may provide sustained pain relief in the long term. Transplantation of GABAergic cells has been successfully used to enhance inhibition and to restore physiological spinal pain processing. However, since the underlying mechanism of chronic pain development involves changes in several pain-signaling pathways, it is essential to develop an approach that targets several components of pain signaling. Recombinant cell therapy offers the possibility to deliver additional analgesic substances to the restricted area in the nervous system. The current study explores the analgesic potential of genetically modified rat embryonic GABAergic cells releasing a peptidergic NMDA receptor antagonist, Serine(1)-histogranin (SHG). Overactivation of glutamate NMDA receptors contributes to the hyperexcitability of spinal neurons observed in chronic pain models. Our approach allows us to simultaneously target spinal hyperexcitability and reduced inhibitory processes. Transplantable cells were transduced by viral vectors encoding either one or six copies of SHG cDNAs. The analgesic potential of recombinant cells after their intraspinal transplantation was evaluated in a model of peripheral nerve injury. Enhanced reduction of hypersensitivity to thermal and mechanical stimuli was observed in animals treated by recombinant cells compared to the nonrecombinant group. The recombinant peptide was detected in the spinal tissue, suggesting its successful production by transplanted cells. Our results demonstrate the feasibility of using recombinant cells releasing adjunct
Mohamad Ali Hijazi
Full Text Available Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.
El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla
Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome. PMID:28280516
Johnson, Sarah; Coxon, Matthew
Virtual reality (VR) technology may serve as an effective non-pharmacological analgesic to aid pain management. During VR distraction, the individual is immersed in a game presented through a head-mounted display (HMD). The technological level of the HMD can vary, as can the use of different input devices and the inclusion of sound. While more technologically advanced designs may lead to more effective pain management the specific roles of individual components within such systems are not yet fully understood. Here, the role of supplementary auditory information was explored owing to its particular ecological relevance. Healthy adult participants took part in a series of cold-pressor trials submerging their hand in cold water for as long as possible. Individual pain tolerances were measured according to the time (in seconds) before the participant withdrew their hand. The concurrent use of a VR game and the inclusion of sound was varied systematically within participants. In keeping with previous literature, the use of a VR game increased pain tolerance across conditions. Highest pain tolerance was recorded when participants were simultaneously exposed to both the VR game and supplementary sound. The simultaneous inclusion of sound may therefore play an important role when designing VR to manage pain.
Objective: To evaluate the analgesic activity of ibuprofen against paracetamol using a simple pain model. Design: A double-blind study. Setting: Twenty general practitioners in Harare, Zimbabwe. Patients: Adults with acute sore throat of a maximum of two days' duration. Interventions: One hundred and thirteen patients with ...
Pascal H Vuilleumier
Full Text Available Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain.In a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo. The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation, and pain during cuff algometry.For the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (p<0.001, but not after clobazam and clonazepam. Results suggestive for an anti-hyperalgesic effect of the benzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed.Collectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental
Vuilleumier, Pascal H.; Besson, Marie; Desmeules, Jules; Arendt-Nielsen, Lars; Curatolo, Michele
Background and Aims Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam) were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain. Methods In a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo). The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation), and pain during cuff algometry. Results For the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (pbenzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed. Conclusions Collectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental models for future investigation of GABAergic compounds. Trial
El Hamsas El Youbi, Amal; El Mansouri, Latifa; Boukhira, Smahane; Daoudi, Abdeljlil; Bousta, Dalila
This study is designed to evaluate the analgesic and anti-inflammatory activities of aqueous extract (AE) of Cistus ladanifer L. leaves in experimental animal models. The central analgesic activity of C. ladanifer AE is studied using hot plate method in rats, and the acute anti-Inflammatory activity of C. ladanifer is investigated by rats paw edema induced by subplantar injection of 0.5% carrageenan into the right hind paw. Rats are pretreated with AE of C. ladanifer at different doses (150, 175, and 200 mg/kg, i.p.). The tramadol and indomethacin are used as reference drugs for analgesic and anti-inflammatory studies, respectively. Our results show that the AE of C. ladanifer exhibited anti-inflammatory and analgesic effects dose dependent. In anti-inflammatory activity, the AE of C. ladanifer at all doses reduced significantly the edema paw inflammation after carrageenan injection. Furthermore at 200 mg/kg, the effect of AE is highly important than that of other doses. In addition, the same AE demonstrates significant analgesic effect in thermal-induced pain model. So, this activity is proved by significant reduction of pain score after administration of AE at all doses. The nociception protection effects in this case are, respectively, 70.3%, 74.55%, and 93.33% after administration of AE of C. ladanifer at doses 150, 175, and 200 mg/kg b.w. The results of our findings suggest that AE of C. ladanifer has potential analgesic and anti-inflammatory activities with evidence of possible involvement of peripheral and central effects in its actions.
Kristensen, David M; Mazaud-Guittot, Séverine; Gaudriault, Pierre; Lesné, Laurianne; Serrano, Tania; Main, Katharina M; Jégou, Bernard
Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Dayanand M Kannur
Full Text Available In the present work, Caesalpinia bonduc seed coat extract (CBSCE has been evaluated for anti-inflammatory and analgesic activity C. bonduc seeds have been attributed with anti-inflammatory and analgesic properties in the folklore medicine. Here in our study, we have tried to carry out the systematic evaluation of the seed coat extract of C. bonduc to substantiate these claims. C. bonduc seed coat was extracted with 95% ethanol and concentrated; further, the extract was screened for anti-inflammatory and analgesic activity. The studies were carried using Carrageenan-induced Paw Edema, Egg albumin-induced paw edema, Eddy′s Hot Plate Test, Tail Immersion Method so as to prove acclaimed properties. The data was analyzed statistically by Students′ ′t′ test. The results indicate that seed coat extract has the ability to decrease the induced inflammation at varied doses in Carrageenan model as well as in the Egg albumin model in rats. The antinociceptive results indicate that the extract has the ability to increase the pain threshold of the animals and reduce the pain factor, thereby inducing analgesia. Thus, it can be concluded that CBSCE posses analgesic and anti-inflammatory activity.
Kannur, Dayanand M.; Paranjpe, Mukta P.; Sonavane, Lalit V.; Dongre, Prerana P.; Khandelwal, Kishanchand R.
In the present work, Caesalpinia bonduc seed coat extract (CBSCE) has been evaluated for anti-inflammatory and analgesic activity C. bonduc seeds have been attributed with anti-inflammatory and analgesic properties in the folklore medicine. Here in our study, we have tried to carry out the systematic evaluation of the seed coat extract of C. bonduc to substantiate these claims. C. bonduc seed coat was extracted with 95% ethanol and concentrated; further, the extract was screened for anti-inflammatory and analgesic activity. The studies were carried using Carrageenan-induced Paw Edema, Egg albumin-induced paw edema, Eddy's Hot Plate Test, Tail Immersion Method so as to prove acclaimed properties. The data was analyzed statistically by Students’ ‘t’ test. The results indicate that seed coat extract has the ability to decrease the induced inflammation at varied doses in Carrageenan model as well as in the Egg albumin model in rats. The antinociceptive results indicate that the extract has the ability to increase the pain threshold of the animals and reduce the pain factor, thereby inducing analgesia. Thus, it can be concluded that CBSCE posses analgesic and anti-inflammatory activity. PMID:23057003
Struyf, F.; Nijs, J.; Meeys, M.; Meuffels, D.; Vries, de, W.; Voogt, L.P.
BACKGROUND: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic effects of manual therapy on peripheral joints have not been systematically reviewed. METHODS: A systematic review was carried out following the PRISMA-guidelines. Manual therapy was defined as any ma...
Postoperatively, duration of analgesia, number of rescue analgesics, signs of any magnesium toxicity, and incidence of postpartum eclampsia in the first 24 h were recorded. Data were ... There was no significant respiratory depression, Apgar score was comparable, and uterine tonicity was adequate in both the groups.
The study was conducted from December, 2013 to May, 2014 on 12 healthy bitches presented to the University of Gondar Teaching Veterinary Clinic for ovariohysterectomy to compare the epidural analgesic efficacy of bupivacaine alone and bupivacaine with tramadol to relieve postoperative pain and asses changes on ...
Feb 8, 2016 ... Drug Industry and Trade Company, Istanbul, Turkey was administered intraperitoneally to all rats for 5 days. Formation of groups and drug ..... Siegmund E, Cadmus R, Lu G. Screening of analgesics, including aspirin‑type compounds, based upon the antagonism of chemically induced writhing in mice.
The methanol and aqueous extract of Allium ascalonicom were investigated for analgesic and anti-inflammatory properties. Thermal and chemical models of pain assessment were used while albumin was used to induce inflammation. The extracts were administered at doses of 50, 100 and 200 mg/kg. The methanol extract ...
(morphine – 250 µg subcutaneously; nimodipine – 100 µg intraperitoneally) after systemic administration. Ni- modipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not ...
Results: The level of pain reported and use of analgesics dropped significantly after the electrotherapy course, compared to the control group. Walking ability improved significantly in patients reporting pain relief. There was no statistically significant difference between the results obtained in the Type 1 and Type 2 patients.
The ethanol extract (200 mg/kg) significantly (P < 0.01) reversed yeast-induced fever. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, flavonoids, saponins, glycosides, terpenoids, tannins, proteins and carbohydrates. Keywords: Sansevieria trifasciata , Analgesic activity, Antipyretic ...
Kumawat, Ram Kumar; Kumar, Suresh; Sharma, Sunil
Sida tiagii Bhandari mostly found in India and Pakistan which belongs to family Malvaceae, is traditionally used as analgesic, anti-inflammatory, sedative, anxiolytic, anti-seizure and anti-platelet. The present study was done to explore the analgesic activity of various extracts of fruits of the plant Sida tiagii Bhandari. The grinded fruits were extracted with 90% ethanol and partitioned with n-hexane (n-hexane extract; HS) and ethyl acetate (ethyl acetate extract; EAS), successively. The residual ethanol fraction (residual ethanol extract; RES) was also prepared by drying on water bath separately. All three extracts were administered orally at a dose of 200 mg/kg and 500 mg/kg of body weight. The analgesic activity of above extracts was evaluated by using acetic acid induced writhing, tail immersion and tail flick tests in Swiss albino mice. The EAS extract was found to reduce pain and RES extract of Sida tiagii B. was found to have good analgesic activity in comparison to other extracts.
Xu, Bo; Wang, Zhi-Ping; Wang, Yan-Juan; Lu, Pei-Hua; Wang, Li-Jun; Wang, Xiao-Hai
Opioid analgesics are the most common therapeutic analgesic for acute pain. In this study, the toxicological and pharmacological features of a group of opioid analgesics were characterized by the motility of human sperm. Aliquots of sperm were incubated with various concentrations of opioid analgesics in vitro. Computer-assisted sperm analysis was used to assess sperm motility at 15 minutes, 2 hours, and 4 hours after drug addition to the medium. Butorphanol and dezocine showed marked reduction of motility after incubation with sperm for 15 minutes. Butorphanol was more effective than dezocine in immobilizing sperm. Other opioids studied, such as fentanyl, alfentanil, and sufentanil, showed only partial inhibitory activity. Based on the data reported herein, we have found that butorphanol and dezocine exert a sperm-immobilizing effect. However, fentanyl, alfentanil, and sufentanil exhibit only partial inhibition of sperm motility. Given the increasing use of opioids and their potential effect on sperm motility, these findings are greatly relevant to male reproductive health.
induced writhing test. The anti-inflammatory effect was assessed using rat paw edema model elicited by fresh egg white and the mouse ear edema model caused by dimethylbenzene. The antipyretic effect was determined using the ...
Full Text Available The study was aimed to evaluate the analgesic and anti-inflammatory effect of aqueous root extracts of Dendrocnide sinuata (Blume Chew (AEDS in Swiss albino mice and wistar rats. The animals were orally administered AEDS at doses 30 and 100 mgkg-1 (p.o. For analgesic study, acetic acid-induced Writhing test, Eddy’s hot plate and Tail Flick model was performed in mice. For antiinflammatory study, carrageen-induced paw edema study was performed in rats. In acetic acid induced model, effect of AEDS was comparable with the standard meloxicam 10 mgkg-1 (i.p. In the hot plate model, the maximum effect was observed at 30 min at a dose of 100 mgkg-1 (p.o which was comparable with the standard Pentazocine 10 mgkg-1 (p.o, whereas in the tail flick model no significant changes were observed. In the carrageenan-induced paw edema model, administration of AEDS showed significant (P < 0.05 dose dependent inhibition of edema formation. AEDS was effective in both narcotic and non-narcotic models of analgesia. It also showed a significant dose-dependent increase in antiedematogenic activity which revealed good peripheral anti-inflammatory properties of the extract.
Voicu, Victor A; Mircioiu, Ion; Sandulovici, Roxana; Mircioiu, Constantin; Plesa, Cristina; Velescu, Bruno S; Anuta, Valentina
Previous studies indicated that addition of the antihistaminic chlorpheniramine to the usual combination of acetylsalicylic acid, acetaminophen, and caffeine further increases their synergism both in terms of anti-inflammatory and analgesic effect. The present non-interventional study tested the superiority of two Algopirin® tablets, containing a total of 250 mg acetylsalicylic acid (ASA), 150 mg acetaminophen (paracetamol, PAR), 30 mg caffeine (CAF) and 4 mg chlorpheniramine (CLF) vs. a combination containing 250 mg ASA, 250 mg PAR, and 65 mg CAF recognized as "safe and effective" by FDA in treating migraine. Patients evaluated their pain intensity on the Visual Analog Scale-VAS(PI) before and 30, 60, 120, 180, and 240 min after drug intake. Interpretation of the pain curves as "survival pain curves" was considered as a method for direct comparison of the pain curves. This interpretation permitted the application of the log rank test for comparison of pain hazards. The results of the applied parametric and non-parametric statistical tests indicated significant differences between the main endpoints: both Areas Under Pain Curves and time to decrease of the pain intensity to less than 50% of the initial value comparisons highlighted that Algopirin® was more efficient in spite of smaller doses of PAR and CAF. Comparison of "survival of pain" led to the same conclusion concerning the superiority of Algopririn. Consequently, the addition of CLF permitted decreasing of ASA, PAR, and CAF doses as well as their potential side effects, without a loss of analgesic effect.
Full Text Available Background and Aim: Long-term consumption of many drugs followed by reduction of their effectiveness has necessitated performing research on new analgesics .Thus, the present study was conducted to evaluate the analgesic effects of mentha longifolia and morphine in mice using writhing and hot plate tests. Materials and Methods: In this experimental study, 70 male rats were divided into 7 equal groups. The groups included the control, three experimental groups receiving 400, 800, or 1600 mg/kg of mentha extract and three experimental groups which received 2, 4, or 8 mg/kg of morphine .In order to measure pain, the two acceptable tests, writhing and hot plate tests, were applied. Pain scores were measured at 0, 15, 30, 45 or 60 min after administration of algogenic stimulus. Results: It was found that in hot plate test, only the dose of 1600mg/kg of Mentha extract after 60 minutes was significantly able to exert an analgesic effect (P<0.05. In wrighting test, mentha extract at different doses significantly reduced the number and time of wrightes in the rats, comparable to morphine (P<0.05. Conclusion: It seems that all doses of mentha extract in wrighting test have analgesic effects which indicate chronic pain inhibition of mentha hydroalcholic extract.
Full Text Available Purpose : Abutilon indicum (Linn. sweet (Malvaceae commonly called ′Country Mallow′ is a perennial plant up to 3 m in height. It is abundantly found as a weed in the sub-Himalayan tract and in the hotter parts of India. The plant is traditionally used for treatment of several diseases like bronchitis, body ache, toothache, jaundice, diabetes, fever, piles, leprosy, ulcers, cystitis, gonorrhea, diarrhea, and so on. Abutilon indicum Linn. is reported to have hepatoprotective, hypoglycemic, antimicrobial, male contraceptive, and antidiarrheal activities. The present study was done to evaluate the analgesic potential of various extracts of the root of Abutilon indicum Linn. Materials and Methods : The powdered root (900 g was subjected to successive solvent extraction, with solvents in increasing order of polarity, namely, petroleum ether (60 - 80C, methanol, and ethanol, using the soxhlet apparatus for 72 hours. The marc was extracted by cold maceration for 72 hours, to obtain a water-soluble extract. The peripheral analgesic activity was studied using acetic acid-induced writhing method in Swiss albino mice (20 - 30 g, while the central analgesic activity was evaluated by the tail flick method and the tail immersion method. Results : Results indicated that all the tested extracts, except the methanol extract, exhibited significant analgesic activity in both animals′ models. Petroleum ether extract showed higher analgesic activity. The activity may be related to the central mechanism or may be due to the peripheral analgesic mechanisms. Conclusion : The present study authenticates the traditional use.
Sakeena, M H F; Yam, M F; Elrashid, S M; Munavvar, A S; Azmin, M N
Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.
NSAIDs) is associated with significant side effects - gastrointestinal lesions, bleeding and nephrotoxicity. Therefore, the discovery of new safer antiinflammatory drugs represents a challenging goal for this research area. Methods: Various derivatives ...
Full Text Available Background. Methylene blue (MB has been found to have unique analgesic property through temporary disruption of sensory nerve conduction. In anorectal surgery, MB is widely used as a biologic stain but the analgesic effect has never been studied. Thus, a literature review completed with critical appraisal is required to find out its efficacy. Methods. A review has been run to find out its efficacy. Literature search proceeded in database sites, namely, PubMed, EBSCO, Cochrane, Wiley, and ProQuest using the following keywords: “anorectal” OR “hemorrhoid” OR “anal fistula” OR “anal fissure” OR “anal abscess” OR “anal pruritus” AND “methylene blue” AND “analgesic”; then the critical appraisal and its implication were discussed. Result. There were 491 articles in full text found, and four studies met the inclusion criteria. Two studies were focused on the evaluation of VAS in hemorrhoid surgery whereas the rest were focused on the evaluation of symptom score in anal pruritus. Conclusions. A study with level of evidence 2 on VAS showed the efficacy. The rest showed insufficient evidence due to variations of anorectal surgery and the methods and techniques of MB application. A further prospective clinical study is required.
Hajhashemi, Valiollah; Ghannadi, Alireza; Hajiloo, Mohammad
Extracts obtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folk medicine as remedies for the treatment of some inflammatory diseases. In this study the hydroalcoholic extract and essential oil of the plant were investigated for its possible anti-inflammatory and analgesic activities. The extract was administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essential oil were 100, 200 and 400 μL/kg. The acetic acid-induced writhing response, formalin-induced paw licking time in the early and late phases and light tail flick test were used in mice to assess analgesic activity. For evaluation of anti-inflammatory effect carrageenan-induced paw edema served as a valid animal model in rats. The extract significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and also showed potent analgesic effect in both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extract significantly (P < 0.05) reduced carrageenan-induced paw edema. Essential oil of the plant at all administered doses failed to show any analgesic or anti-inflammatory effect in above mentioned tests. These results provide support for the use of hydroalcoholic extract of Rosa damascena in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.
Intraventricular morphine administration is indicated, in some selected cases, to alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal fluid allowed us to formulate the theory of "Front de Recrutement". Then we were able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6-glucuronide concentrations. Morphine 6-glucuronide is the main analgesic metabolite of morphine and its presence in cerebro-spinal fluid could be due to a metabolism of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher than that of morphine. By demonstrating the 6-monoacetyl morphine potency (analgesic metabolite of heroin that is 20 times more potent than morphine), we showed the involvement of the 6 position in the analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin, morphine must be considered as a precursor whose metabolites have pharmacologic effects.
Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun
In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain. Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not
Gupta, Richa; Kaur, Jagjit
Cordia dichotoma G. Forst. is an important medicinal plant of family Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and joint pain but its medicinal activities have not been proven by research. To evaluate the analgesic, anti-inflammatory, and antipyretic activity of C. dichotoma G. Forst. leaf extract. The various extracts of leaf powder were prepared by using soxhlet apparatus. The methanol extract was selected for pharmacological study. To evaluate analgesic activity, Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia method was used. SD female rats (180-200 g) were used for the study. In all three tests, the methanol extract high dose (400 mg/kg) was found to be highly significant as compared to standard drug. This study proved the traditional uses of plant leaves and concluded the analgesic, anti-inflammatory, and antipyretic activity of the leaf methanol extract.
Full Text Available Irritable bowel syndrome (IBS is a functional bowel disorder that causes recurrent abdominal (visceral pain. Epidemiological data show that the incidence rate of IBS is as high as 25%. Most of the medications may lead to tolerance, addiction and toxic side effects. Moxibustion is an important component of traditional Chinese medicine and has been used to treat IBS-like abdominal pain for several thousand years in China. As a mild treatment, moxibustion has been widely applied in clinical treatment of visceral pain in IBS. In recent years, it has played an irreplaceable role in alternative medicine. Extensive clinical studies have demonstrated that moxibustion for treatment of visceral pain is simple, convenient, and inexpensive, and it is being accepted by an increasing number of patients. There have not been many studies investigating the analgesic mechanisms of moxibustion. Studies exploring the analgesic mechanisms have mainly focused on visceral hypersensitivity, brain-gut axis neuroendocrine system, and immune system. This paper reviews the latest developments in moxibustion use for treatment of visceral pain in IBS from these perspectives. It also evaluates potential problems in relevant studies on the mechanisms of moxibustion therapy to promote the application of moxibustion in the treatment of IBS.
Rasool Soltani; Hossein Vatanpour; Fatemeh Shafiee; Niloofar Sadeghian
Background: Opioid drugs are the most effective drugs for the treatment of moderate to severe pain. Rates of opioid use are influenced by a variety of factors. The aim of this study was to determine the pattern of use of parenteral opioid drugs in hospitalized patients in a referral teaching hospital. Methods: In a retrospective study, required data were extracted from medical records of adult patients who had received any parenteral opioid analgesic in the 6-month period from March 2013 to S...
B. Jahangiri R. Jahangiri
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.
Byager, N; Hansen, Mads; Mathiesen, Ole
BACKGROUND: Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post......-operative pain after breast surgery. METHODS: A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery...... significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. CONCLUSION: Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild...
Ezeja, Mi; Omeh, Ys; Ezeigbo, Ii; Ekechukwu, A
Dialium guineense is a medicinal plant used by some communities of Enugu-Ezike in Enugu State, Nigeria for treatment of fever, headache and other diverse ailments. The present study evaluated the analgesic activity of the methanolic stem bark extract of the plant. Acetic acid-induced abdominal constriction or writhing, tail immersion and hot plate analgesic models in albino Wistar mice were used for the study. Three test doses (250, 500, 1000 mg/kg body weight) of the extract were administered orally by gastric gavage. The activity was compared with a standard reference drug, acetylsalicylic acid (aspirin) (400 mg/kg) and negative control. The results were analysed by SPSS version 17 using ANOVA and Post Hoc Duncan. In the acetic acid-induced writhing reflex model, D. guineense extract and the reference drug significantly (P =0.014 - 0.002) decreased the mean total number of abdominal constriction in the mice in a dose dependent fashion. The percentage inhibition of the abdominal constriction reflex was increased dose dependently from 0% in the negative control group to 71% at the highest dose of the extract (1000mg/kg). In the tail immersion model the extract at the dose of 1000 mg/kg significantly (P = 0. 048) increased the pain reaction time (PRT) while in hot plate model the extract and drug also significantly (P = 0.048 - 0.05) increased the mean PRT at the doses of 500 and 1000 mg/kg. The dose of 250 mg/kg showed no analgesic activity in tail immersion and hot plate models. Dialium guineense demonstrated significant analgesic activity that may be mediated through peripheral pain mechanism.
Full Text Available CO(2-laser C-fibre evoked cortical potentials (LCEPs is a potentially useful animal model for studies of pain mechanisms. A potential confounding factor when assessing analgesic effects of systemically administered drugs using LCEP is sedation. This study aims to clarify: 1 the relation between level of anaesthesia and magnitude of LCEP, 2 the effects of a sedative and an analgesic on LCEP and dominant EEG frequency 3 the effects of a sedative and analgesic on LCEP when dominant EEG frequency is kept stable. LCEP and EEG were recorded in isoflurane/nitrous-oxide anaesthetized rats. Increasing isoflurane level gradually reduced LCEPs and lowered dominant EEG frequencies. Systemic midazolam (10 μmol/kg profoundly reduced LCEP (19% of control and lowered dominant EEG frequency. Similarly, morphine 1 and 3 mg/kg reduced LCEP (39%, 12% of control, respectively and decreased EEG frequency. When keeping the dominant EEG frequency stable, midazolam caused no significant change of LCEP. Under these premises, morphine at 3 mg/kg, but not 1 mg/kg, caused a significant LCEP reduction (26% of control. In conclusion, the present data indicate that the sedative effects should be accounted for when assessing the analgesic effects of drug. Furthermore, it is suggested that LCEP, given that changes in EEG induced by sedation are compensated for, can provide information about the analgesic properties of systemically administrated drugs.
Full Text Available Background/Aim. Ropivacaine is a relatively new longacting local anesthetic. The aim of this study was to compare the postoperative analgesic effect of topical anesthetics ropivacaine 0.75% and lidocaine 2% with adrenaline in the postoperative treatment of periapical lesions in the maxilla. Methods. The study was conducted on 60 subjects, divided into two groups. The study-group received 0.75% ropivacaine without a vasoconstrictor, while the control group was treated with 2% lidocaine with adrenaline (1 : 80.000. Block anesthesia for n. infraorbitalis was used and local anesthetics were applied also on the palatine side for the end branches of n. nasopalatinus. The following parameters were observed: time elapsed from the application of an anesthetic until the first occurrence of pain after the surgery and first intake of an analgesic, the intensity of initial pain, pain intensity 6 h after the application of anesthetics and the total number of analgesics taken within 24 h after the completion of surgery. Results. The pain appeared statistically significantly earlier in the patients who had been given lidocaine with adrenaline (p < 0.001, while statistically significantly higher mean values of initial postoperative pain (p < 0.05 and pain intensity 6 h after the intervention (p < 0.01 were also registered in the same group of patients. In the period of 24 h upon the intervention, the study-group patients were taking less analgesics as compared to the control-group subjects (46.6% vs 73.3%, who were given analgesics earlier, although no statistically significant differences were observed related to the number of analgesic doses taken. Conclusion. The results of our study indicate a better postoperative analgesic effect of ropivacaine as compared to lidocaine with adrenaline.
Henriksen, Marius; Hansen, Julie B; Klokker, Louise
AIM: Evidence of comparative effectiveness of different treatment approaches is important for clinical decision-making, yet absent for most recommended treatments of knee osteoarthritis pain. The objective of this study was to estimate the comparative effectiveness of exercise versus orally.......34-0.59). There was no statistically significant difference between the two types of intervention (difference: 0.06 standardized mean difference [95% CI: -0.28-0.16; p = 0.61]). CONCLUSION: This meta-epidemiological study provides indirect evidence that for knee osteoarthritis pain, the effects from exercise and from oral analgesics...... administered analgesics for pain in patients with knee osteoarthritis. METHODS: The Cochrane Database of systematic reviews was searched for meta-analyses of randomized controlled studies comparing exercise or analgesics with a control group (placebo or usual care) and with pain as an outcome. Individual study...
Mahmoud Reza Alebouyeh
Full Text Available Background: Opiate is used in patient-controlled intravenous analgesia pumps (PCIA for controlling pain in post-surgical patients. Other drugs are remarkably added to opioid pumps to enhance quality, lengthen analgesia, and reduce side effects. Lidocaine, a local anesthetic which inhibits sodium channels, has anesthetic and analgesic effects when injected locally or intravenously. The objective of this study is to evaluate the analgesic effects of adding lidocaine 1% to different doses of morphine via IV pump to patient-controlled analgesia (PCA after orthopedic surgeries. Materials and Methods: In a randomized clinical trial, 60 patients who had undergone orthopedic surgery of lower extremities were divided into three equal groups to control postoperative pain. Intravenous pump with 5 ml/h flow rate was used as the analgesic method. The solution consisted of lidocaine 1% plus 20 mg morphine for the first group, lidocaine 1% plus 10 mg morphine for the second group, and only 20 mg morphine for the third group (control group. Patients were checked every 12 h, and Visual Analog Scale (VAS, extra opioid doses, nausea/vomiting, and sedation scale were examined. Results: Pain score was lower in the first group compared to the other two groups. Mean VAS was 2.15 ± 0.2, 2.75 ± 0.2, and 2 ± 0.25 on the first day and 1.88 ± 0.1, 2.74 ± 0.3, and 2.40 ± 0.3 on the second day, respectively, in the three groups and the difference was statistically significant (P < 0.01 and <0.05, respectively. Also, 10% of patients in the first group needed extra opioid doses, while this figure was 30% in the second group and 25% in the third group (P < 0.01. Nausea/vomiting and sedation scores were not statistically different among the three groups. Conclusion: Compared to lidocaine 1% plus 10 mg morphine or 20 mg morphine alone in PCIA, adding lidocaine 1% to 20 mg morphine decreases the pain score and opioid dose after orthopedic surgeries without having side
Warne, Leon N; Beths, Thierry; Holm, Merete; Carter, Jennifer E; Bauquier, Sébastien H
To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. 2-phase positive-controlled randomized masked clinical trial. 39 healthy female cats (10 in phase 1 and 29 in phase 2). Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.
The peripheral effect of two analgesics (aspirin and dibencozide) was studied on anaesthetized cats. Several types of neurons and stimulations were performed in this work: traction for periodontal mechanoreceptors connected to small-sized trigeminal fibres, distension for the muscular intestinal mechanoreceptors connected to non-myelinated vagal fibres, chemical stimulation by means of phenyldiguanide for the non-myelinated vagal fibres, electrical stimulation of the myelinated and non-myelinated vagal fibres. In all cases, unitary activities were recorded into corresponding ganglia (nodose or gasserian) with extracellular glass microelectrodes. After injection of analgesics, a decrease of control responses were observed till 30 minutes but the maximum occurred between 1 and 5 minutes. This effect concerned the non-myelinated neurones as well as the myelinated ones. It can be explained by a direct action of analgesics on the ending excitability.
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Song, Tieying; Wang, Liwen; Gu, Kunfeng; Yang, Yunliang; Yang, Lijun; Ma, Pengyu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyv; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian
Thalidomide was introduced to the market in 1957 as a sedative and antiemetic agent, and returned to the market for the treatment of myelodysplastic syndrome and multiple myeloma. There are reports and studies of thalidomide as an analgesic or analgesic adjuvant in clinic. However, the underlying mechanism is quite elusive. Many studies suggest that the analgesic effect of thalidomide may be due to its immunomodulatory and anti-inflammatory properties as it suppresses the production of tumor necrosis factor α (TNF-α) selectively. However, it is not clear whether any other mechanisms are implicated in the pain relief. In this study, we demonstrated that the peripheral vanilloid receptor 1 (TRPV1) channel was also involved in the analgesic effect of thalidomide in different cell and animal models. During the activation by its agonist capsaicin, the cation inward influx through TRPV1 channels and the whole-cell current significantly decreased after TRPV1-overexpressed HEK293 cells or dorsal root ganglion (DRG) neurons were pre-treated with thalidomide for 20 minutes. And such attenuation in the TRPV1 activity was in a dose-dependent manner of thalidomide. In an acetic acid writhing test, pre-treatment of thalidomide decreased the writhing number in the wild type mice, while it did not happen in TRPV1 knockout mice, suggesting that the TRPV1 channel was involved in the pain relief by thalidomide. Taken together, the study showed that TRPV1 channels were involved in the analgesic effects of thalidomide. Such alteration in the action of TRPV1 channels by thalidomide may help understand how thalidomide takes analgesic effect in the body in addition to its selective inhibition of TNF-α production. Copyright © 2015 Elsevier Ltd. All rights reserved.
Guria, Tanmoy; Singha, Tanushree; Maity, Tapan Kumar
A variety of active constituents with wide range of pharmacological actions have been reported with Centella asiatica. The present study was undertaken to assess analgesic and anti-inflammatory properties of its leaf extracts. Dried leaves were defatted with petroleum ether and extracted with chloroform and methanol. Both chloroform and methanol extracts were evaluated for analgesic activity through tail clip, tail flick, tail immersion, and writhing assay tests at doses of 50, 100, and 200 mg/kg using Swiss albino mice. On the other hand, anti-inflammatory assay was performed by carrageenan induced paw edema of methanol extract at 100 and 200 mg doses in Wistar albino rat. Dextropropoxyphene and indomethacin were employed as a standard for analgesic and anti-inflammatory studies, respectively. Our present study demonstrated that Centella asiatica bears significant analgesic and anti-inflammatory activities in those models. PMID:24369507
Voogt, Lennard; de Vries, Jurryt; Meeus, Mira; Struyf, Filip; Meuffels, Duncan; Nijs, Jo
Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic effects of manual therapy on peripheral joints have not been systematically reviewed. A systematic review was carried out following the PRISMA-guidelines. Manual therapy was defined as any manual induced articular motion with the aim of inducing analgesic effects. Outcome measure was pain threshold. A total of 13 randomized trials were included in the review. In 10 studies a significant effect was found. Pressure pain thresholds increased following spinal or peripheral manual techniques. In three studies both a local and widespread analgesic effect was found. No significant effect was found on thermal pain threshold. Moderate evidence indicated that manual therapy increased local pressure pain thresholds in musculoskeletal pain, immediately following the intervention. No consistent result was found on remote pressure pain threshold. No significant changes occured on thermal pain threshold values. The clinical relevance of these effects remains contradictory and therefore unclear. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Objective: Pure analgesics are only rarely used by Italian clinicians and this holds true also for rheumatologists. This work is concerned with an evaluation of the use of analgesics in a rheumatological outpatient clinic during the period 1989-1999. Methods: The records of 1705 patients consecutively seen at the clinic were downloaded on a specifically built website. Results: 4469 visits were considered. In 260 of them (5.8%, analgesics were prescribed to 234 (13.7% patients. The number of patients with a prescription of analgesics steadily increased during the years 1989-1999. The diagnoses in patients assuming analgesics were: osteoarthritis (47.1%, inflammatory arthritis (24.2%, soft tissue rheumatisms (13.7%, nonspecific arthralgia/myalgia (7.5%, and connective tissue diseases (2.6%. Peripheral analgesics were used in 188 (82.5% patients and central analgesics were used in the remaining 40 patients (17.5%. Analgesic drugs were used mainly in degenerative joint conditions. The indications for analgesics in the 55 patients with inflammatory arthrits were: (a partial or total remission of arthritis; for this reason non-steroidal anti-inflammatory drugs were no longer required in 18 patients; (b to increase the analgesic effect of NSAIDs in 23 patients; (c contraindications to NSAIDs in 14 patients (renal failure in 2 patients, gastritis in 10, allergy and bleeding in the remaining two. Conclusions: About 14% of our outpatients were treated with analgesics with an increasing trend in the examined period. The main indications for analgesics are degenerative conditions but they can be used also in selected patients with arthritis.
Mohammad Ahmadi Soleimani, S; Azizi, Hossein; Mirnajafi-Zadeh, Javad; Semnanian, Saeed
Long-term administration of opiates leads to development of tolerance to analgesic effects. This in turn compromise clinical use of these drugs for pain management. Although extensive studies have been conducted, the involved cellular mechanisms are still poorly understood. The nucleus locus coeruleus (LC), which is a dense homogenous cluster of noradrenergic neurons in brainstem, has been reported to be involved in mediating opiate effects including analgesia and tolerance. LC neurons express a high density of opioid receptors. On the other hand, orexinergic neurons send widespread projections to the LC region. Among the two types of orexin receptors (OX1R and OX2R), OX1R is highly expressed in LC neurons. It has been shown that orexin-A is involved in modulation of nociceptive behavior. Also, previous studies have demonstrated the involvement of OX1R in the development of morphine induced analgesia and tolerance. In the present study, the involvement of OX1R in development of met-enkephalin (ME) analgesic tolerance was investigated in LC nucleus. The tail flick test was used to evaluate the analgesic effect of intra-LC microinjection of ME in male Wistar rats (250-300g). Analgesic responses were reported as the percentage of maximum possible effect (% of MPE). Also, SB-334867 was used as a selective OX1R antagonist. Results indicate that intra-LC microinjection of ME (5μg/100nL) results in development of analgesic tolerance in 3days. Also, OX1R antagonism in LC nucleus significantly prevents the analgesic effect of intra-LC met-enkephalin microinjection. It appears that the analgesic effect of ME in LC neurons is mediated by orexinergic system. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available David Castel,1 Itai Sabbag,2 Sigal Meilin3 1The Neufeld Cardiac Research Institute, Sheba Medical Centre, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 2Lahav Research Institute, Kibutz Lahav, Negev, 3Neurology R&D Division, MD Biosciences, Nes-Ziona, Israel Abstract: Interest in the development of new topical/local drug administration for blocking pain at peripheral sites, with maximum drug activity and minimal systemic effects, is on the rise. In the review article by Kopsky and Stahl, four critical barriers in the process of research and development of topical analgesics were indicated. The active pharmaceutical ingredient (API and the formulation are among the major challenges. The road to the development of such drugs passes through preclinical studies. These studies, if planned correctly, should serve as guidance for choosing the right API and formulation. Although rodent models for pain continue to provide valuable data on the mechanisms driving pain, their use in developing topical and localized treatment approaches is limited for technical (intraplate injection area is small as well as mechanical reasons (non-similarity to human skin and innervation. It has been previously shown that pigs are comparable to humans in ways that make them a better choice for evaluating topical and local analgesics. The aim of this study was to summarize several experiments that used pigs for testing postoperative pain in an incisional pain model (skin incision [SI] and skin and muscle incision [SMI]. At the end of the surgery, the animals were treated with different doses of bupivacaine solution (Marcaine®, bupivacaine liposomal formulation (Exparel® or ropivacaine solution (Naropin. Von Frey testing demonstrated a decrease in the animals’ sensitivity to mechanical stimulation expressed as an increase in the withdrawal force following local treatment. These changes reflect the clinical condition in the level as well as in the duration of
O'Neil, Christine K; Hanlon, Joseph T; Marcum, Zachary A
Osteoarthritis (OA) is the most common cause of disability in older adults, and although analgesic use can be helpful, it can also result in adverse drug events. To review the recent literature to describe potential adverse drug events associated with analgesics commonly used by older adults with OA. To identify articles for this review, a systematic search of the English-language literature from January 2001 to June 2012 was conducted using PubMed, MEDLINE, EBSCO, and the Cochrane Database of Systematic Reviews for publications related to the medical management of OA. Search terms used were "analgesics," "acetaminophen," "nonsteroidal anti-inflammatory drugs" (NSAIDs), "opioids," "pharmacokinetics," "pharmacodynamics," and "adverse drug events." The search was restricted to those articles that concerned humans aged ≥65 years. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that examined analgesic use in older adults. There are limited data to suggest that non-frail elders are more likely than their younger counterparts to develop acetaminophen-induced hepatotoxicity. However, decreased hepatic phase II metabolism in frail elders may result in increased risk of hepatotoxicity. It is now well established that older adults are at higher risk of NSAID-induced gastrointestinal toxicity and renal insufficiency. Insofar as opioids, the data that suggest an increased risk of falls, fractures, or delirium need to be tempered by the potential risk of inadequately treating severe chronic OA-related pain. Acetaminophen is the mainstay frontline analgesic for treating OA-related pain in older adults. NSAIDs should be limited to short-term use only, and for moderate to severe OA-related pain, opioids may be preferable in individuals without substance abuse or dependence issues. Copyright © 2012
Desaphy, Jean-François; Dipalma, Antonella; De Bellis, Michela; Costanza, Teresa; Gaudioso, Christelle; Delmas, Patrick; George, Alfred L; Camerino, Diana Conte
Orphenadrine is a drug acting on multiple targets, including muscarinic, histaminic, and NMDA receptors. It is used in the treatment of Parkinson's disease and in musculoskeletal disorders. It is also used as an analgesic, although its mechanism of action is still unknown. Both physiological and pharmacological results have demonstrated a critical role for voltage-gated sodium channels in many types of chronic pain syndromes. We tested the hypothesis that orphenadrine may block voltage-gated sodium channels. By using patch-clamp experiments, we evaluated the effects of the drug on whole-cell sodium currents in HEK293 cells expressing the skeletal muscle (Nav1.4), cardiac (Nav1.5) and neuronal (Nav1.1 and Nav1.7) subtypes of human sodium channels, as well as on whole-cell tetrodotoxin (TTX)-resistant sodium currents likely conducted by Nav1.8 and Nav1.9 channel subtypes in primary culture of rat DRG sensory neurons. The results indicate that orphenadrine inhibits sodium channels in a concentration-, voltage- and frequency-dependent manner. By using site-directed mutagenesis, we further show that orphenadrine binds to the same receptor as the local anesthetics. Orphenadrine affinities for resting and inactivated sodium channels were higher compared to those of known sodium channels blockers, such as mexiletine and flecainide. Low, clinically relevant orphenadrine concentration produces a significant block of Nav1.7, Nav1.8, and Nav1.9 channels, which are critical for experiencing pain sensations, indicating a role for sodium channel blockade in the clinical efficacy of orphenadrine as analgesic compound. On the other hand, block of Nav1.1 and Nav1.5 may contribute to the proconvulsive and proarrhythmic adverse reactions, especially observed during overdose.
Prins, Sandra A.; Van Dijk, Monique; Van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.
Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40
Prins, Sandra A.; van Dijk, Monique; van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.
The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h
Matyas, R A; Mumford, S L; Schliep, K C; Ahrens, K A; Sjaarda, L A; Perkins, N J; Filiberto, A C; Mattison, D; Zarek, S M; Wactawski-Wende, J; Schisterman, E F
Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic
Simavli, Serap; Gumus, Ilknur; Kaygusuz, Ikbal; Yildirim, Melahat; Usluogullari, Betul; Kafali, Hasan
The control of labor pain and the prevention of suffering are major concerns of clinicians and their patients. The aim of this study was to evaluate the effect of music on labor pain and anxiety, maternal hemodynamics, fetal-neonatal parameters and postpartum analgesic requirement in primiparous women. Overall, 156 primiparous women who expected vaginal delivery were recruited and randomly assigned to a music group (n = 77) or a control group (n = 79). Women in the music group listened to music during labor. Pain intensity and anxiety level were measured using a visual analogue scale (0-10 cm). The two groups were compared in terms of pain severity, anxiety level, maternal hemodynamics, fetal-neonatal parameters and postpartum analgesic requirement. Mothers in the music therapy group had a lower level of pain and anxiety compared with those in the control group at all stages of labor (p music therapy group (p music during labor has a positive impact on labor pain and anxiety, maternal-fetal parameters and analgesic requirement. © 2014 S. Karger AG, Basel.
Dogan, Serpil Dagdelen; Ustun, Faik Emre; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Kaya, Cengiz; Ozkan, Fatih
We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. The first group (n=30) received IV lidocaine infusions at a rate of 1.5mg/kg/min and the second group (n=30) received IV esmolol infusions at a rate of 1mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20min following surgical incision (plidocaine group (plidocaine group (plidocaine group at 10 and 20min after extubation (plidocaine group (plidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Andersen, Lars Peter Kloster; Gögenur, Ismail; Torup, Henrik
, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double......-blind, placebo-controlled study investigating the analgesic efficacy of a regional anesthetic block following a major elective surgical procedure were analyzed. The original data included measurements of pain intensity (visual analog scale [VAS]) at rest and during coughing (VAS0/2/4/6/12/18/24 h) and OC0......: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We...
Saki, K; Bahmani, M; Rafieianb-Kopaei, M D; Asadollahi, K; Emaneini, M; Taherikalani, M
The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.
Serpil Dagdelen Dogan
Full Text Available ABSTRACT OBJECTIVE: We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. METHODS: The first group (n = 30 received IV lidocaine infusions at a rate of 1.5 mg/kg/min and the second group (n = 30 received IV esmolol infusions at a rate of 1 mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. RESULTS: In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20 min following surgical incision (p < 0.05. Awakening time was shorter in the esmolol group (p < 0.001; Ramsay Sedation Scale scores at 10 min after extubation were lower in the esmolol group (p < 0.05. The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p < 0.05. The time to attain a modified Aldrete score of ≥9 points was prolonged in the lidocaine group (p < 0.01. Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20 min after extubation (p < 0.05, p < 0.01, respectively. Analgesic supplements were less frequently required in the lidocaine group (p < 0.01. CONCLUSION: In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR scores and time to reach MAR score of 9 points.
Dogan, Serpil Dagdelen; Ustun, Faik Emre; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Kaya, Cengiz; Ozkan, Fatih
We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. The first group (n=30) received IV lidocaine infusions at a rate of 1.5mg/kg/min and the second group (n=30) received IV esmolol infusions at a rate of 1mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20min following surgical incision (p<0.05). Awakening time was shorter in the esmolol group (p<0.001); Ramsay Sedation Scale scores at 10min after extubation were lower in the esmolol group (p<0.05). The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p<0.05). The time to attain a modified Aldrete score of ≥9 points was prolonged in the lidocaine group (p<0.01). Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20min after extubation (p<0.05, p<0.01, respectively). Analgesic supplements were less frequently required in the lidocaine group (p<0.01). In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points. Copyright © 2014. Publicado por Elsevier Editora Ltda.
Ralevski, Elizabeth; Perrino, Albert; Acampora, Gregory; Koretski, Julia; Limoncelli, Diana; Petrakis, Ismene
Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. Forty-eight healthy subjects participated in this study; thirty-one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double-blind, placebo-controlled, randomized, within-subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low-exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high-exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60-minute infusion mark. The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol.
Richardson, Michael G; Lopez, Brandon M; Baysinger, Curtis L; Shotwell, Matthew S; Chestnut, David H
Evidence on the analgesic effectiveness of nitrous oxide for labor pain is limited. Even fewer studies have looked at patient satisfaction. Although nitrous oxide appears less effective than neuraxial analgesia, it is unclear whether labor analgesic effectiveness is the most important factor in patient satisfaction. We sought to compare the relationship between analgesic effectiveness and patient satisfaction with analgesia in women who delivered vaginally using nitrous oxide, neuraxial analgesia (epidural or combined spinal-epidural [CSE]), or both (neuraxial after a trial of nitrous oxide). A standardized survey was recorded on the first postpartum day for all women who received anesthetic care for labor and delivery. Data were queried for women who delivered vaginally with nitrous oxide and/or neuraxial labor analgesia over a 34-month period in 2011 to 2014. Parturients with complete data for analgesia quality and patient satisfaction were included. Analgesia and satisfaction scores were grouped into 8 to 10 high, 5 to 7 intermediate, and 0 to 4 low. These scores were compared with the use of ordinal logistic regression across 3 groups: nitrous oxide alone, epidural or CSE alone, or nitrous oxide followed by neuraxial (epidural or CSE) analgesia. A total of 6507 women received anesthesia care and delivered vaginally. Complete data were available for 6242 (96%) women; 5261 (81%) chose neuraxial analgesia and 1246 (19%) chose nitrous oxide. Of the latter, 753 (60%) went on to deliver with nitrous oxide alone, and 493 (40%) switched to neuraxial analgesia. Most parturients who received neuraxial analgesia (>90%) reported high analgesic effectiveness. Those who used nitrous oxide alone experienced variable analgesic effectiveness, with only one-half reporting high effectiveness. Among all women who reported poor analgesia effectiveness (0-4; n = 257), those who received nitrous oxide alone were more likely to report high satisfaction (8-10) than women who received
Peng, Xiaoxue; Studholme, Keith; Kanjiya, Martha P; Luk, Jennifer; Bogdan, Diane; Elmes, Matthew W; Carbonetti, Gregory; Tong, Simon; Gary Teng, Yu-Han; Rizzo, Robert C; Li, Huilin; Deutsch, Dale G; Ojima, Iwao; Rebecchi, Mario J; Puopolo, Michelino; Kaczocha, Martin
Background Fatty-acid-binding proteins (FABPs) are intracellular carriers for endocannabinoids, N-acylethanolamines, and related lipids. Previous work indicates that systemically administered FABP5 inhibitors produce analgesia in models of inflammatory pain. It is currently not known whether FABP inhibitors exert their effects through peripheral or central mechanisms. Here, we examined FABP5 distribution in dorsal root ganglia and spinal cord and examined the analgesic effects of peripherally and centrally administered FABP5 inhibitors. Results Immunofluorescence revealed robust expression of FABP5 in lumbar dorsal root ganglia. FABP5 was distributed in peptidergic calcitonin gene-related peptide-expressing dorsal root ganglia and non-peptidergic isolectin B4-expressing dorsal root ganglia. In addition, the majority of dorsal root ganglia expressing FABP5 also expressed transient receptor potential vanilloid 1 (TRPV1) and peripherin, a marker of nociceptive fibers. Intraplantar administration of FABP5 inhibitors reduced thermal and mechanical hyperalgesia in the complete Freund's adjuvant model of chronic inflammatory pain. In contrast to its robust expression in dorsal root ganglia, FABP5 was sparsely distributed in the lumbar spinal cord and intrathecal administration of FABP inhibitor did not confer analgesic effects. Administration of FABP inhibitor via the intracerebroventricular (i.c.v.) route reduced thermal hyperalgesia. Antagonists of peroxisome proliferator-activated receptor alpha blocked the analgesic effects of peripherally and i.c.v. administered FABP inhibitor while antagonism of cannabinoid receptor 1 blocked the effects of peripheral FABP inhibition and a TRPV1 antagonist blocked the effects of i.c.v. administered inhibitor. Although FABP5 and TRPV1 were co-expressed in the periaqueductal gray region of the brain, which is known to modulate pain, knockdown of FABP5 in the periaqueductal gray using adeno-associated viruses and pharmacological FABP5
Manchenko, D M; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F
Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.
Background N-type Ca2+ channels (Cav2.2) play an important role in the transmission of pain signals to the central nervous system. ω-Conotoxin (CTx)-MVIIA, also called ziconotide (Prialt®), effectively alleviates pain, without causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects. Results Here we identify a new CTx, FVIA, from the Korean Conus Fulmen and describe its effects on pain responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat model. CTx-FVIA (10 ng) also showed significant analgesic effects on writhing in mouse neurotransmitter- and cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-γ induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after administration, pressure recovered faster and to a greater degree after CTx-FVIA administration. Conclusions The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low side effects. PMID:21172037
Kim Hyun Jeong
Full Text Available Abstract Background N-type Ca2+ channels (Cav2.2 play an important role in the transmission of pain signals to the central nervous system. ω-Conotoxin (CTx-MVIIA, also called ziconotide (Prialt®, effectively alleviates pain, without causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects. Results Here we identify a new CTx, FVIA, from the Korean Conus Fulmen and describe its effects on pain responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat model. CTx-FVIA (10 ng also showed significant analgesic effects on writhing in mouse neurotransmitter- and cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-γ induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after administration, pressure recovered faster and to a greater degree after CTx-FVIA administration. Conclusions The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low side effects.
(1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type
Rogerio, Alexandre P; Fontanari, Caroline; Melo, Mirian C C; Ambrosio, Sérgio R; de Souza, Glória E P; Pereira, Paulo S; França, Suzelei C; da Costa, Fernando B; Albuquerque, Deijanira A; Faccioli, Lúcia H
Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the anti-inflammatory activity of the same L. pacari extract in mice injected intraperitoneally with beta-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by beta-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation.
Røjskjaer, Jesper O; Gade, Erik; Kiel, Louise B
OBJECTIVE: To assess the effect of bilateral ultrasound-guided transversus abdominis plane block with ropivacaine compared with placebo as part of a multimodal analgesic regimen. DESIGN: A randomized, double-blind, placebo-controlled trial following the CONSORT criteria. SETTING: Hvidovre...... an ultrasound-guided transversus abdominis plane block in women undergoing total abdominal hysterectomy. As part of a multimodal regimen the transversus abdominis plane block showed some effect on pain scores at rest only in the early postoperative period....
Lalinde, N; Moliterni, J; Wright, D; Spencer, H K; Ossipov, M H; Spaulding, T C; Rudo, F G
The synthesis and intravenous analgesic activity of a series of 3-methyl-4-(N-phenyl amido)piperidines, entries 34-79, is described. The methoxyacetamide pharmacophore produced a series of compounds with optimal analgesic potency and short duration of action. cis-42 was 13,036 times more potent than morphine and 29 times more potent than fentanyl; however, the corresponding diastereomer 43 was only 2778 and 6 times more potent, respectively. Compounds 40, 43, 47, and 57 are extremely short acting; all had durations of action of about 2 min, which was about 1/5 of that of fentanyl in the mouse hot-plate test at a dose equivalent to 2 times the ED50 analgesic dose. Among the many compounds that displayed exceptional analgesic activity, duration of action was one of the main factors for choosing a candidate for further pharmacological investigation. At present, cis-1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-3-meth yl-4- [N-in equilibrium 2-fluorophenyl)methoxyacetamido]piperidine hydrochloride (40) (Anaquest, A-3331.HCl, Brifentanil) is in clinical evaluation. Opiate analgesics that possess short duration of action are excellent candidates for short surgical procedures in an outpatient setting where a rapid recovery is required.
Full Text Available Introduction. This study aimed to determine if preoperative psychological tests combined with simple pain prediction ratings could predict pain intensity and analgesic usage following cesarean delivery (CD. Methods. 50 healthy women undergoing scheduled CD with spinal anesthesia comprised the prospective study cohort. Preoperative predictors included 4 validated psychological questionnaires (Anxiety Sensitivity Index (ASI, Fear of Pain (FPQ, Pain Catastrophizing Scale, and Eysenck Personality Questionnaire and 3 simple ratings: expected postoperative pain (0–10, anticipated analgesic threshold (0–10, and perceived analgesic needs (0–10. Postoperative outcome measures included post-CD pain (combined rest and movement and opioid used for the 48-hour study period. Results. Bivariate correlations were significant with expected pain and opioid usage (r=0.349, anticipated analgesic threshold and post-CD pain (r=-0.349, and perceived analgesic needs and post-CD pain (r=0.313. Multiple linear regression analysis found that expected postoperative pain and anticipated analgesic needs contributed to post-CD pain prediction modeling (R2=0.443, p<0.0001; expected postoperative pain, ASI, and FPQ were associated with opioid usage (R2=0.421, p<0.0001. Conclusion. Preoperative psychological tests combined with simple pain prediction ratings accounted for 44% and 42% of pain and analgesic use variance, respectively. Preoperatively determined expected postoperative pain and perceived analgesic needs appear to be useful predictors for post-CD pain and analgesic requirements.
Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits.It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesic effects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesic effects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network.
Full Text Available Cancer-induced bone pain (CIBP is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE, isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin, has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP.
Taylor, A; Oyedeji, O O; Aremu, O; Oyemitan, I; Gwebu, E T; Oyedeji, A O; Nkeh-Chungag, B N
Determination of the active fraction and compounds of the dichloromethanol extract of Schinus molle seeds and evaluation of their biological effects. Dried seeds of Schinus molle were sequentially extracted in hexane, acetyl acetate and dichloromethane. The dichloromethane extract was separated into two fractions (1 and 2) by column chromatography. Fraction 2 was further separated into its two constituent compounds which were characterized as belonging to the lanosteroid group of compounds. Both factions were tested for their analgesic, anti-inflammatory and sedative effects. The two fractions significantly increased (p<0.05) the tail flick latency though fraction 2 provided better and more long lasting protection against thermal pain. On the other hand, the anti-inflammatory effect of ibuprofen, though inferior to the anti-inflammatory effect of fraction 2 was better than the effects of fraction 1. Fraction 2 significantly (p<0.01) reduced rat paw oedema compared to the saline treatment group throughout the experiments while fraction 2 compared to fraction 1 showed significantly (p<0.01) greater inflammatory effects. On the other hand both fractions lacked significant sedative effects. Given that fraction 2 had only two constituent compounds (isomasticadienonic and Masticatrienonate), one or both of these compounds should be contributing to the observed analgesic and anti-inflammatory effects.
Shih, Andre C; Robertson, Sheilah; Isaza, Natalie; Pablo, Luisito; Davies, Wendy
To compare the analgesic effects of buprenorphine, carprofen, and their combination in dogs undergoing ovariohysterectomy. Prospective, randomized blinded clinical study. 60 dogs. Treatments were buprenorphine 0.02 mg kg(-1), intramuscularly (IM) (group B); carprofen 4 mg kg(-1), subcutaneously (SC) (group C); or a combination of both (group CB). Anesthesia was induced with propofol and maintained with isoflurane. A Dynamic Interactive Visual Analog Scale (DIVAS, 0-100 mm) and the Glasgow Composite Pain Scale (GCMPS, 0-24) were used to evaluate comfort and sedation at baseline, 2, 4, 6, and 24 hours after extubation. Rescue analgesia was provided with buprenorphine (0.02 mg kg(-1)). Wound swelling measurements (WM) and a visual inflammation score (VIS) of the incision were made after surgery and 2, 4, 6, and 24 hours later. p < 0.05 was considered significant. Group C required more propofol (5.0 +/- 1.4 mg kg(-1)) compared with B (3.3 +/- 1.1 mg kg(-1)) and CB (3.2 +/- 0.7 mg kg(-1)); respectively, p = 0.0002 and 0.0001. Rescue analgesia was required in nine dogs. B had a higher GCMPS and DIVAS III score at 6 hours (2.6 +/- 2.5) and (23 +/- 22.5 mm) compared with C (1.0 +/- 1.3, 6 +/- 7.3 mm) and CB (1.5 +/- 1.4, 8 +/- 10.7 mm); respectively, p = 0.02 and 0.006. Group C had a lower sedation score at 2 hours (43 +/- 23.6 mm) compared with B (68 +/- 32.1 mm) and BC (69 +/- 22.1 mm); respectively, p = 0.03 and 0.004. Group B had a higher WM score at 2 hours (3 +/- 0.8 mm) compared with C (2 +/- 0.6 mm) p = 0.01 and at 6 hours (3 +/- 1 mm) compared with C (2 +/- 0.8 mm) and CB (2 +/- 0.8 mm); respectively, p = 0.01 and 0.008. VIS was not different between groups. All treatments provided satisfactory analgesia for the first 6 hours and at 24 hours. C and CB pain score and WS were superior to B at 6 hours. No superior analgesic effect was noted when the drugs were combined.
The leaves of Acalypha wilkesiana are commonly used for the treatment of pain, fever and ulcer by traditional medical practitioners without any scientific data to evaluate ... Different sets of rats were used for the anti-ulcer, anti-inflammatory and antipyretic studies although animal grouping for extract administration were as in ...
Full Text Available Diffuse noxious inhibitory control (DNIC is described as one possible mechanism of acupuncture analgesia. This study investigated the analgesic effect of acupuncture without stimulation compared to nonpenetrating sham acupuncture (NPSA and cold-pressor-induced DNIC. Forty-five subjects received each of the three interventions in a randomized order. The analgesic effect was measured using pressure algometry at the second toe before and after each of the interventions. Pressure pain detection threshold (PPDT rose from 299 kPa (SD 112 kPa to 364 kPa (SD 144, 353 kPa (SD 135, and 467 kPa (SD 168 after acupuncture, NPSA, and DNIC test, respectively. There was no statistically significant difference between acupuncture and NPSA at any time, but a significantly higher increase of PPDT in the DNIC test compared to acupuncture and NPSA. PPDT decreased after the DNIC test, whereas it remained stable after acupuncture and NPSA. Acupuncture needling at low pain stimulus intensity showed a small analgesic effect which did not significantly differ from placebo response and was significantly less than a DNIC-like effect of a painful noninvasive stimulus.
Wiech, K; Kalisch, R.; Weiskopf, N; Pleger, B.; Stephan, K. E.; Dolan, R. J.
Perceived control attenuates pain and pain-directed anxiety, possibly because it changes the emotional appraisal of pain. We examined whether brain areas associated with voluntary reappraisal of emotional experiences also mediate the analgesic effect of perceived control over pain. Using functional magnetic resonance imaging, we compared self-controlled noxious stimuli with physically identical stimuli that were externally controlled. Self-controlled stimulation was accompanied by less pain a...
Wei, Wei; Tian, Yanli; Zhao, Chunlei; Sui, Zhifu; Liu, Chang; Wang, Congmin; Yang, Rongya
Background Our study aimed to explore the association between β1-adrenoceptor (ADRB1) rs1801253 polymorphism and analgesic effect of fentanyl after cancer surgeries in Chinese Han populations. Material/Methods Postoperative fentanyl consumption of 120 patients for analgesia was recorded. Genotype distributions were detected by allele specific amplification-polymerase chain reaction (ASA-PCR) method. Postoperative pain was measured by visual analogue scale (VAS) method. Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were compared by analysis of variance (ANOVA). Preoperative cold pressor-induced pain test was also performed to test the analgesic effect of fentanyl. Results Frequencies of Gly/Gly, Gly/Arg, Arg/Arg genotypes were 45.0%, 38.3%, and 16.7%, respectively, and passed the Hardy-Weinberg Equilibrium (HWE) test. The mean arterial pressure (MAP) and the heart rate (HR) had no significant differences at different times. After surgery, the VAS score and fentanyl consumption in Arg/Arg group were significantly higher than in other groups at the postoperative 2nd hour, but the differences were not obvious at the 4th hour, 24th hour, and the 48th hour. The results suggest that the Arg/Arg homozygote increased susceptibility to postoperative pain. The preoperative cold pressor-induced pain test suggested that individuals with Arg/Arg genotype showed worse analgesic effect of fentanyl compared to other genotypes. Conclusions In Chinese Han populations, ADRB1 rs1801253 polymorphism might be associated with the analgesic effect of fentanyl after cancer surgery. PMID:26694722
Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E
Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.
Yi, Yusheng; Zhao, Mingqiang; Xu, Fenghe; Liu, Chuansheng; Yin, Yanwei; Yu, Junmin
Purpose: Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. Methods: 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. Results: The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (Pfentanyl consumption of the C/C group was much higher than the T/T group (Pfentanyl consumption of the C/C group was more than the T/C group (Pfentanyl consumption for analgesia. PMID:26191294
modulatory effects of dezocine-propofol, and fentanyl-propofol combinations in colonoscopy. Methods: One hundred and thirty-four patients who received painless colonoscopy in Eastern Medical District of Linyi People's Hospital, Linyi City, ...
Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn
In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no w......In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice......, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists...... reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h...
Kane, F M A; Brodie, E E; Coull, A; Coyne, L; Howd, A; Milne, A; Niven, C C; Robbins, R
Vascular wounds may require frequent dressing changes over a long period of time, often involving pain, which may not be adequately controlled with conventional analgesia. Complementary analgesia may be beneficial as an adjunctive therapy. This pilot study presented eight patients with two odour therapies, lavender and lemon, two music therapies, relaxing and preferred music and a control condition, during vascular wound dressing changes. Although the therapies did not reduce the pain intensity during the dressing change there was a significant reduction in pain intensity for the lavender therapy and a reduction in pain intensity for the relaxing music therapy after the dressing change. This supports the use of these complementary therapies, which are inexpensive, easy to administer and have no known side effects, as adjunctive analgesia in this patient population. Earlier administration before dressing change may enhance these effects. Further research is required to ascertain why certain complementary therapies are more effective than others at relieving pain.
Haemoglobin, Packed cell volume, total erythrocyte and leukocyte counts showed a significant (p<0.05) ..... leading to a direct depressant effect on brain stem respiratory centres. (Tranquilli et al., 2004). Tramadol was .... Adjunctive drug therapy for canine osteoarthritis pain. Proceeding of the North American Veterinary ...
, while 400 mg/kg produced more inhibitory effects. At 2, 3 and 5 h post carrageenan injection, 200 and 400 mg/kg extract significantly inhibited paw edema. The extract dose dependently suppressed kaolin-carrageenan-induced edema from 3 ...
Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.
Knotkova, Helena; Nitsche, Michael A.; Cruciani, Ricardo A.
Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits. It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analge...
Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi
Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
Ferrari, Renata; Zanolin, Maria E; Duse, Genni; Visentin, Marco
There is general agreement about the need to perform a screening test to assess the risk of opioid misuse prior to starting a long-term opioid treatment for chronic noncancer pain. The evidence supporting the effectiveness of opioid long-term treatment is weak, and no predictors of its usefulness have been assessed. The aim of this study was to assess the effect on pain and quality of life of chronic opioid treatment, and detect the possible predictors of its effectiveness. This observational, prospective study was conducted in 2 Italian Pain Relief Units on 77 patients affected by intractable chronic pain. Patients were submitted to psycho-logical tests, investigating the individual pain experience, risk of opioid misuse, mood states, quality of life, and personality characteristics prior to starting treatment and at 2,4, and 6-month follow-up. Both maximum and habitual pain, as measured with VAS, underwent a statistically significant reduction at 2, 4, and 6-month follow-up. In multivariate analysis, lower scores in the Pain Medication Questionnaire (PMQ) were predictive of a major reduction in maximum VAS (P = 0.005). Both low PMQ and MMPI-cynicism scores were predictive of habitual VAS decrease (P = 0.012 and P = 0.028, respectively). The results indicate that pain relief significantly improved over a 6-month period of opioid treatment, together with quality of life. The outcome was better in patients with a pretreatment low risk of opioid misuse, low scores in the Cynicism scale of MMPI-2, and no aberrant drug behaviors at follow-up. Therefore, a psychological screening and support is crucial for a good outcome of opioid therapy for chronic noncancer pain patients.
Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan
Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.
Solhaug, Vigdis; Molden, Espen
As pain is often a comorbid condition, many patients use opioid analgesics in combination with several other drugs. This implies a generally increased risk of drug interactions, which along with inherent pharmacogenetic variability and other factors may cause differences in therapeutic response of opioids. To provide an overview of interactions and pharmacogenetic variability of relevance for individual differences in effect and tolerability of opioid analgesics, which physicians and other healthcare professionals should be aware of in clinical practice. The article was based on unsystematic searches in PubMed to identify literature highlighting the clinical impact of drug interactions and pharmacogenetics as sources of variable response of opioid analgesics. Cytochrome P450 (CYP)-mediated metabolism is an important process for both clinically relevant interactions and pharmacogenetic variability of several opioids. Concomitant use of CYP inhibitors (e.g. paroxetine, fluoxetine and bupropion) or inducers (e.g. carbamazepine, phenobarbital and phenytoin) could counteract the clinical effect or trigger side effects of analgesics in the same manner as genetically determined differences in CYP2D6-mediated metabolism of many opioids. Moreover, combination treatment with drugs that inhibit or induce P-glycoprotein (ABCB1), a blood-brain barrier efflux transporter, may alter the amount ('dose') of opioids distributed to the brain. At the pharmacodynamic level, it is crucial to be aware of the potential risk of interaction causing serotonergic syndrome when combining opioids and serotonergic drugs, in particular antidepressants inhibiting serotonin reuptake (SSRIs and SNRIs). Regarding pharmacogenetics at the receptor level of pain treatment, the knowledge is currently scarce, but an allelic variant of the μ1 opioid receptor (OPRM1) gene has been associated with higher dosage requirement to achieve analgesia. Drug interactions and pharmacogenetic differences may lead to
Coble, Dondrae J; Taylor, Douglas K; Mook, Deborah M
We evaluated analgesic use and analgesiometry in aquatic African-clawed frogs (Xenopus laevis). We used the acetic acid test (AAT) to assess the analgesic potential of systemic xylazine hydrochloride, meloxicam, flunixin meglumine, and morphine sulfate after injection into the dorsal lymph sac. Flunixin meglumine provided better analgesia than did the other drugs, most evident at 5 and 9 h after administration. Because the AAT was associated with the development of dermal lesions, we discontinued use of this assay and chose the Hargreaves test as an alternative method of measuring nociception in Xenopus. This assay is commonly performed in rodents, but its efficacy in an aquatic species such as Xenopus was unknown prior to this study. We found that the Hargreaves test was an effective measure of nociception in Xenopus, and we used it to evaluate the effectiveness of the nonopiod agents xylazine hydrochloride, meloxicam, and flunixin meglumine both in the absence of surgery and after surgical oocyte harvest. Similar to findings from the AAT, flunixin meglumine provided better analgesia in the Hargreaves test than did the other agents when analyzed in the absence of surgical intervention. Results were equivocal after oocyte harvest. Although surgical oocyte harvest is a common procedure in Xenopus, and currently there are no published recommendations for analgesia after this invasive surgery. Future studies are needed to clarify the efficacy of nonsteroidal antiinflammatory drugs for that purpose.
Jung, Hyun-Suk; Lee, Jungkwon
Primary dysmenorrhea is a common gynecologic disorder, but is often inappropriately managed due to ignorance and misunderstanding of its pharmacotherapy in many young women. The aim of this study was to assess the effectiveness of an educational intervention on proper analgesic use for dysmenorrhea among Korean female university students. In March 2008, an educational intervention, a 10-min lecture using supplementary educational printed materials, was given to the intervention group (n=98). Two months later, changes and differences in knowledge, actual medication behavior, coping strategies, dysmenorrhea severity (VAS score), and Korean health-related quality of life (KQOLS) were assessed between the intervention and control (n=105) groups. The prevalence of dysmenorrhea in the intervention and control groups was 75.1% and 77.1%, respectively. After the educational intervention, the medication rate of the intervention group was significantly increased (from 36.1% to 51.0%, P=0.007), and the knowledge of and actual behavior relating to the proper analgesic use were also significantly improved in this group. The VAS scores were significantly decreased among participants with dysmenorrhea in the intervention group (from 48.6 ± 22.0 to 37.8 ± 22.5, Pintervention group. The findings of this prospective study suggest that a brief educational intervention can improve the severity of dysmenorrhea and the quality of life by enhancing medication knowledge and actual analgesic behavior in Korean female university students. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Angela Maria Sousa
Full Text Available BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl, rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.
Hossain, Ahamed Ismail; Faisal, Mohammad; Rahman, Shahnaz; Jahan, Rownak; Rahmatullah, Mohammed
Background Alternanthera sessilis is used by folk medicinal practitioners of Bangladesh for alleviation of severe pain. The objective of this study was to scientifically analyze the analgesic (non-narcotic) property of aerial parts of the plant along with antihyperglycemic activity. Methods Antihyperglycemic activity was measured by oral glucose tolerance tests. Analgesic (non-narcotic) activity was determined by observed decreases in abdominal writhings in intraperitoneally administered acet...
Kishnani, Sushil; Saha, Suparna Ganguly; Bhardwaj, Anuj; Dubey, Sandeep; Saha, Mainak; Kala, Shubham; Jain, Sohini; Narwani, Shweta
A definitive diagnosis is of primary importance before initiating any endodontic treatment; yet, there are occasions when the dental professional is unable to accurately reproduce the patient's chief complaint, as it can pose a dilemma and may require consideration of multiple variables in order to reach an accurate diagnosis. So to overcome this problem, a methodical approach in providing endodontic treatment should be implemented which includes diagnosis, definitive dental treatment and adjunctive drug therapy, known as the "3D" strategy. The purpose of this study was to evaluate the possible "masking" effect of these analgesics on endodontic diagnosis using a novel bite force sensor device. A total of 90 patients with endodontic pain were selected and they were given either a placebo or 400 mg ibuprofen (brufen) or 50mg diclofenac sodium (voveron). Both patients and operators were completely blinded to the drugs administered. Bite force tolerance values were noted before and one hour after administration of medication using the self designed bite force sensor. The pre- and post-bite force tolerance values were tabulated for both contralateral and affected tooth. For the affected tooth, there was statistically significant difference between pre- and post-bite force tolerance values in Group I (i.e., ibuprofen) and Group II (i.e., diclofenac sodium) (p<0.05) with no significant difference observed in Group III (placebo). The easily available over the counter self administered analgesics in addition to providing symptomatic relief to patients suffering from symptomatic apical periodontitis may also cloud the definitive diagnosis of the clinician, thus jeopardising the treatment plan. The self designed bite force sensor was effective in arriving at a definitive diagnosis in teeth with chronic irreversible pulpitis with symptomatic apical periodontitis, where the allodynia has been camouflaged by the use of analgesics like ibuprofen and diclofenac sodium.
Al-Harrasi, Ahmed; Ali, Liaqat; Hussain, Javid; Rehman, Najeeb Ur; Mehjabeen; Ahmed, Mansoor; Al-Rawahi, Ahmed
To investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain. The crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice. Of 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform/n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform/n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase). The present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties
Irnich, D; Winklmeier, S; Beyer, A; Peter, K
The aim of this pilot study was to investigate the potential value of acupuncture in the treatment of peripheral neuropathic pain. Explorative analysis should provide data for further randomised controlled trials. In an uncontrolled clinical trial electroacupuncture was given to 17 patients with chronic neuropathic pain of peripheral origin which was resistant to preceding pain therapy. Patients were treated twice weekly for 4 weeks. Assessment of outcome measurements comprised: Intensity of continuous pain (visual analogue scale, VAS), intensity of pain attacks (VAS), duration of pain attacks, number of pain attacks and changes in mood (VAS). All measures were evaluated by diary (1 week before treatment to 2 weeks after treatment and 1 week at follow up three months after treatment). Changes of global complaints and patients' beliefs in treatment (credibility assessment) were also assessed. At re-evaluation two weeks after treatment, mean continuous pain was reduced by 32.9% and intensity of pain attacks was reduced by 59%. Mean number of daily pain attacks decreased from 4.2 (SD +/- 4.6, 0.14-13.3) before treatment to 2.2 (SD +/- 3.8, 0-7.5) two weeks after treatment. Duration of pain attacks and mood showed no substantial changes. Three months after treatment, continuous pain was reduced by 15.9% and intensity of pain attacks was reduced by 44% compared to baseline. No serious adverse events were observed On the basis of this small pilot study, trial treatment by electroacupuncture seems to be justified in these patients given a lack of success of standard treatments. The apparent beneficial analgesic effects of electroacupuncture appear to warrant further investigation.
Walker, D J; Zacny, J P
The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included to test this assumption. Codeine and morphine increased ratings of "feel drug effect" but had little effect on other subjective measures, including the Addiction Research Center Inventory, visual analog scales, and adjective checklists. The few subjective effects that were observed were modest and were dose-related for morphine but not for codeine. The drugs did not affect performance on Maddox-Wing, digit-symbol substitution, coordination, auditory reaction, reasoning, and memory tests. Dose-related decreases in pupil size (miosis) were observed following codeine and morphine. Ratings of pain intensity decreased in a dose-related manner for morphine but not for codeine. Plasma codeine and morphine levels varied as an orderly function of dose. These results suggest that oral codeine and morphine are appropriate drugs for outpatient pain relief because they are effective analgesics at doses that have only modest effects on mood, produce few side effects, and do not impair performance. The results also suggest a possible ceiling effect of codeine on analgesia and subjective effects.
Full Text Available The study was conducted to evaluate the effects of romifidine alone (50 Âµg/kg and a combination of romifidine (50 Âµg/kg and ketamine (2.5 mg/kg after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II. The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 Â±6.25 s compared to that of group I (5.2 Â±0.54 min. Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I and respiratory rate (more pronounced in group II, and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electro-cardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.
Luvisetto, Siro; Vacca, Valentina; Cianchetti, Carlo
We evaluate analgesic effects of BoNT/A in relation to the two main transient receptor potentials (TRP), the vanilloid 1 (TRPV1) and the ankyrin 1 (TRPA1), having a role in migraine pain. BoNT/A (15 pg/mouse) was injected in the inner side of the medial part of hindlimb thigh of mice, where the superficial branch of femoral artery is located. We chosen this vascular structure because it is similar to other vascular structures, such as the temporal superficial artery, whose perivascular nociceptive fibres probably contributes to migraine pain. After an interval, ranging from 7 to 30 days, capsaicin (agonist of TRPV1) or allyl isothiocyanate (AITC; agonist of TRPA1) were injected in the same region previously treated with BoNT/A and nocifensive response to chemicals-induced pain was recorded. In absence of BoNT/A, capsaicin and AITC induced extensive nocifensive response, with a markedly different temporal profile: capsaicin induced maximal pain during the first 5 min, while AITC induced maximal pain at 15-30 min after injection. Pretreatment with BoNT/A markedly reduced both the capsaicin- and AITC-induced pain for at least 21 days. These data suggest a long lasting analgesic effect of BoNT/A exerted via prevention of responsiveness of TRPV1 and TRPA1 toward their respective agonists. Copyright © 2014 Elsevier Ltd. All rights reserved.
Cartagena-Sevilla, Joaquín; García-Fernández, María R; Vicente-Villena, Juan P
The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P pain for a relatively long time.
Bellah, S M Faysal; Islam, Md Nur; Karim, Md Rezaul; Rahaman, Md Masudur; Nasrin, Mst Samima; Rahman, Md Atiar; Reza, A S M Ali
Synthetic drugs are going to be replaced by plant-derived traditional drugs due to their cost effectiveness, relatively less harmfulness, and efficacy against multidrug resistance organisms. Hygrophila spinosa (Acanthaceae) has been used in a wide range of ailments including flatulence, diarrhea, dysentery, gonorrhea, and menorrhagia. Therefore, we investigated the cytotoxic, antinociceptive, and antidiarrheal effects of H. spinosa ethanol extract (EExHs). Preliminary phytochemical screening was accomplished by established methods modified in experimental protocol. EExHs was undertaken for cytotoxic assay by Brine shrimp lethality bioassay, antinociceptive action by acetic acid induced writhing test, and antidiarrheal activity by castor oil induced antidiarrheal test. Data were analyzed by GraphPad Prism 6.0 software using Dunnett's test for multiple comparisons. Reducing sugar, steroid, glycoside, tannin, alkaloid, saponins, and flavonoids were found to be present in EExHs. Lethal concentration (LC50) of EExHs for brine shrimps was 50.59 µg/mL which was relatively lower than that of the standard drug vincristine sulfate. In acetic acid induced writhing test, oral administration of EExHs at three different doses (125, 250, and 500 mg/kg) decreased writhing in dose-dependent manner while the highest dose (500 mg/kg) achieved the maximum percentages of pain inhibition (58.8%). Diclofenac sodium (25 mg/kg) was used as a reference antinociceptive drug. The antidiarrheal action of EExHs was not found to be very promising for further use; however, the pure compounds from EExHs could be analyzed to justify the effects. This research demonstrates that the secondary metabolites guided cytotoxic and analgesic effects could be extensively studied in multiple models to confirm the effects.
Full Text Available The optimization of pain management following surgery with minimal side effects, is one the major goals of surgical and medical teams. In this randomized double blind study, sixty ASA (American Society of Anesthesiologist class I or II patients, undergoing urological surgery, were assessed to receive either pethidine or tramadol using a standard method for general anesthesia. Pain intensity was assessed by verbal rating, through a 4-step scaling system. Results of this investigation have revealed that the mean total drug administered in tramadol group were 244.53 + 56.95 mg and in pethidine group 176.78+42.99 mg respectively. There were no significant differences in analgesic effect, observed in either group during early hours following surgery, but after 8,12 and 16 hours significant differences were observed. Analgesic properties of tramadol were almost comparable with pethidine nevertheless; pethidine was superior in some extent. No significant differences in patient’s PaO2 were found, but PaCO2 at 1 and 4 hours after surgery had a greater retention in pethidine group. (P<0.001. There was a significant reduction in respiratory rate in pethidine group at 4,8,12 and 16 hours following surgery, compared with tramadol group (P<0.001. Incidence of dizziness was greater in patients who received pethidine (P<0.001, and sweating was higher in tramadol group (P<0.01. Also there was a greater need for metoclopramide to overcome nausea in tramadol group (P<0.05. Results of this study may suggest that tramadol could be considered as a safe and effective analgesic, following urological surgery as compared with pethidine
Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A
The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. Copyright © 2013 Elsevier Ltd. All rights reserved.
Baudesson de Chanville, Audrey; Brevaut-Malaty, Véronique; Garbi, Aurélie; Tosello, Barthelemy; Baumstarck, Karine; Gire, Catherine
Two studies have demonstrated an analgesic effect of maternal milk odor in preterm neonates, without specifying the method of olfactory stimulation. Research aim: This study aimed to assess the analgesic effect of maternal milk odor in preterm neonates by using a standardized method of olfactory stimulation. This trial was prospective, randomized, controlled, double blinded, and centrally administered. The inclusion criteria for breastfed infants included being born between 30 and 36 weeks + 6 days gestational age and being less than 10 days postnatal age. There were two groups: (a) A maternal milk odor group underwent a venipuncture with a diffuser emitting their own mother's milk odor and (2) a control group underwent a venipuncture with an odorless diffuser. The primary outcome was the Premature Infant Pain Profile (PIPP) score, with secondary outcomes being the French scale of neonatal pain-Douleur Aiguë du Nouveau-né (DAN) scale-and crying duration. All neonates were given a dummy. Our study included 16 neonates in the maternal milk odor group and 17 in the control group. Neonates exposed to their own mother's milk odor had a significantly lower median PIPP score during venipuncture compared with the control group (6.3 [interquartile range (IQR) = 5-10] versus 12.0 [IQR = 7-13], p = .03). There was no significant difference between the DAN scores in the two groups ( p = .06). Maternal milk odor significantly reduced crying duration after venipuncture (0 [IQR = 0-0] versus 0 [IQR = 0-18], p = .04). Maternal milk odor has an analgesic effect on preterm neonates.
Mayahara, Masako; Foreman, Marquis D; Wilbur, JoEllen; Paice, Judith A; Fogg, Louis F
Nonprofessional caregivers frequently experience barriers to using analgesics for pain in patients in home hospice settings, and patients in pain may suffer needlessly. For example, caregiver adherence to the administration of analgesics is lower for as-needed (PRN) regimens than for standard around-the-clock regimens. But little is known about the barriers caregivers experience and the effects of those barriers. Accordingly, we determined caregiver barriers to using analgesics to manage the pain of patients in the home hospice care setting, and how such barriers affected caregiver adherence and patient quality of life. To this end, we measured barriers, caregiver adherence to PRN analgesic regimens, and patient health outcomes (pain, depression, quality of life [QoL]). A 3-day longitudinal design was used. We recruited 46 hospice nonprofessional caregiver-patient dyads from a local community hospice agency. Barriers were measured with the Barrier Questionnaire II. Adherence to the PRN analgesic regimen was obtained with a 3-day pain and medication diary. Patient outcome measures included pain intensity, the Hospital Depression Scale, and the Brief Hospice Inventory for QoL. Barrier scores were moderate to low. Caregivers adhered to PRN analgesic regimens approximately 51% of the time. Higher caregiver adherence to PRN analgesic regimens was associated with lower patient pain intensity and higher patient QoL, but not, surprisingly, with barriers to pain management. Longitudinal studies are now needed to identify factors besides caregiver barriers that may unduly lower caregiver adherence to PRN analgesic regimens. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
Webb, J; Kamali, F
The analgesic activity of a single dose of lamotrigine (300 mg p.o.) and phenytoin (300 mg p.o.) was evaluated in a randomised, double-blind, placebo-controlled study in 12 healthy volunteers. A computerised cold-pressor test (CPT) was used to measure analgesia. Dihydrocodeine (90 mg p.o.) was used to validate the effectiveness of the CPT in measuring analgesia in the volunteers. On each study day the volunteers performed the CPT before study medication and at 1.25, 2.75, 4.25 and 5.75 h post-dose. Psychomotor tests were carried out before each CPT to determine possible drug-induced sedation. These included digit symbol substitution, critical flicker fusion and choice reaction time. Subjective feelings of concentration, vigilance and relaxation were also measured using visual analogue scales. All three active drugs significantly reduced pain scores. Maximum pain relief was achieved at 1.25 h post-dose for both dihydrocodeine and lamotrigine, whereas for phenytoin it occurred at 4.25 h post-dose. There was a significant association between analgesia and plasma concentrations of lamotrigine (P = 0.013) and phenytoin (P = 0.028). There were no significant differences in the sedation produced by any of the active drugs, compared to placebo. The findings of this study suggest that lamotrigine and phenytoin could have a wider clinical use as analgesics.
Md. Razibul Habib
Full Text Available Objective: To evaluate the analgesic, neuropharmacological, cytotoxic and thrombolytic potentials of the aqueous, ethanol and ethyl acetate extracts of Kalanchoe pinnata leaves. Methods: At the dose of 400 mg/kg body weight, the analgesic activity of the extracts were evaluated by the acetic acid-induced writhing and formalin-induced persistent pain tests while neuropharmacological activity was evaluated by the open field, hole cross and elevated plus maze tests. The cytotoxic potential was observed by brine shrimp lethality bioassay and the thrombolytic potential was investigated by clot lysis test. Results: The aqueous extract significantly suppressed the number of writhing (96.78% as well as the formalin-induced persistent pain on the early phase (46.92% and on the late phase (40.98%. Again in case of hole cross and open field tests, the locomotor activity was decreased significantly (P < 0.001 mostly by the ethyl acetate extract. Furthermore, the sedative-anxiolytic activity was supported by the increased percent (P < 0.01 of frequency into the open arm on elevated plus maze test. Besides, the extracts showed moderate lethality and thrombolytic activity. Conclusions: The findings showed that activities are comparable to the standards and in some cases are stronger than the standards. Therefore, based on the results, it is evident that it has great analgesic and sedative-anxiolytic activity with moderate cytotoxic and thrombolytic potential.
Tammisto, T; Tigerstedt, I
One hundred patients, who were in pain during the immediate postoperative period after upper abdominal operations, were included in this double-blind, between-patient, two-dose study. During N2O-O2-halothane-relaxant anaesthesia no analgesics were given. The patients received 0.07 mg/kg or 0.14 mg/kg of nalbuphine or 0.3 mg/kg or 0.6 mg/kg of pentazocine by intravenous injection. Pain and side effects were assessed for 4 h after administration of the test drug, or until the pain returned to the pre-injection level, when a conventional analgesic was given. The onset of pain relief was similar and the peak effect occurred about half an hour after the injection after both drugs. On a milligram basis, nalbuphine seemed to be about three times as potent as pentazocine. The duration of action seemed to be slightly longer after nalbuphine, but 2 1/2 hrs. after the injection the pain had returned to preinjection level in 2/3 of the patients, even after the higher doses of both drugs. Except for sleepiness, there were few side effects and they were similar after both drugs. No psychotomimetic effects were observed.
Mohammad Hosein Bakhshaei
Full Text Available The quality of subarachnoid block can be improved by adding opioids to the local anesthetics. We compared the analgesic effects of different doses of intrathecal sufentanil added to lidocaine %5 for elective cesarean section. This study was a prospective, randomized, double-blind, controlled trial. 90 pregnant women with ASA class I-II, scheduled for elective cesarean section under spinal anesthesia were enrolled in this study. Three groups were made of them by random; Group 1 (control group was given lidocaine 5% (75 mg and 2 ml of normal saline. Patients in Group 2 received lidocaine 5% (75 mg and 5 micrograms sufentanil plus 1ml normal saline. Group 3 patients received lidocaine 5% (75 mg and 10 micrograms sufentanil. Duration of sensory block and effective analgesia (need to analgesic were measured. Opioid related side effects were recorded. Duration of sensory block and effective analgesia were prolonged in sufentanil groups in comparison of control group(50.3±4 that was significantly more in group3 (128 ± 4 versus group 2 (58.3 ± 10(P
Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge
Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses. Copyright © 2017 Elsevier B.V. All rights reserved.
Jang, Jae-Hwan; Park, Ji-Yeun; Oh, Ju-Young; Bae, Sun-Jeong; Jang, Hyunchul; Jeon, Songhee; Kim, Jongpil; Park, Hi-Joon
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH -/- mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH +/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly increased mechanical and thermal pain thresholds in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH in both pain models, suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal grey. The MCH1R antagonist abolished the effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.
Dezhang Lu1,2, Chenchen Wu1, Yupeng Yin1* and Xinwu Ma1,2*
Full Text Available In this study, the analgesia effects of intravenous injection either of lidocaine, fentanyl, or their combination were compared in dogs undergoing ovariohysterectomy. Forty-eight dogs were randomly assigned into three groups. Anesthesia was induced with 6 mg/kg propofol and maintained with 2% (vaporizer dial setting isoflurane. Animals received lidocaine (4 mg/kg, fentanyl (3 μg/kg, and their combination after 15 minutes of induction. Heart rhythm, respiratory rhythm, blood pressure, rectal temperature, subjective pain scores and arterial blood-gas were measured at same time. Cardiopulmonary variables changed after injection, and some of them had significant differences compared with baselines at the moment of extubation. The maximal subjective pain scores were recorded at three hours after extubation, but rescue analgesic was not required at this study. Though values regarding blood gas changed after intravenous administration of agents, significant differences were not found between groups at any of the time-points. Both drugs and their combination provided adequate analgesia undergoing ovariohysterectomy in dogs. No side effects were observed, no rescue analgesic was required.
Mohammad M. Hassan
Full Text Available Aim: The research was carried out to investigate the analgesic and anti-inflammatory effects of ethanol extract of Desmodium pauciflorum, Mangifera indica and Andrographis paniculata leaves. Materials and Methods: In order to assess the analgesic and anti-inflammatory effects acetic acid induced writhing response model and carrageenan induced paw edema model were used in Swiss albino mice and Wistar albino rats, respectively. In both cases, leaves extract were administered (2gm/kg body weight and the obtained effects were compared with commercially available analgesic and anti-inflammatory drug Dclofenac sodium (40mg/kg body weight. Distilled water (2ml/kg body weight was used as a control for the study. Results: In analgesic bioassay, oral administration of the ethanol extract of leaves were significantly (p<0.01 reduced the writhing response. The efficacy of leaves extract were almost 35% in Desmodium pauciflorum, 56% in Mangifera indica and 34% in Andrographis paniculata which is found comparable to the effect of standard analgesic drug diclofenac sodium (76%. Leaves extract reduced paw edema in variable percentages but they did not show any significant difference among the leaves. Conclusion: We recommend further research on these plant leaves for possible isolation and characterization of the various active chemical substances which has the toxic and medicinal values. [Vet World 2013; 6(2.000: 68-71
Abdel Shaheed, Christina; Maher, Chris G; Williams, Kylie A; Day, Richard; McLachlan, Andrew J
Opioid analgesics are commonly used for low back pain, however, to our knowledge there has been no systematic evaluation of the effect of opioid dose and use of enrichment study design on estimates of treatment effect. To evaluate efficacy and tolerability of opioids in the management of back pain; and investigate the effect of opioid dose and use of an enrichment study design on treatment effect. Medline, EMBASE, CENTRAL, CINAHL, and PsycINFO (inception to September 2015) with citation tracking from eligible randomized clinical trials (RCTs). Placebo-controlled RCTs in any language. Two authors independently extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The primary outcome measure was pain. Pain and disability outcomes were converted to a common 0 to 100 scale, with effects greater than 20 points considered clinically important. Of 20 included RCTs of opioid analgesics (with a total of 7925 participants), 13 trials (3419 participants) evaluated short-term effects on chronic low back pain, and no placebo-controlled trials enrolled patients with acute low back pain. In half of these 13 trials, at least 50% of participants withdrew owing to adverse events or lack of efficacy. There was moderate-quality evidence that opioid analgesics reduce pain in the short term; mean difference (MD), -10.1 (95% CI, -12.8 to -7.4). Meta-regression revealed a 12.0 point greater pain relief for every 1 log unit increase in morphine equivalent dose (P = .046). Clinically important pain relief was not observed within the dose range evaluated (40.0-240.0-mg morphine equivalents per day). There was no significant effect of enrichment study design. For people with chronic low back pain who tolerate the medicine, opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important
Full Text Available Purpose: In this study the intensity and duration of analgesic effect of diclofenac Na - Eudragit® RS100 solid dispersion and nanoparticles were evaluated by using formalin test in the rats. Methods: The animals received different formulations of diclofenac Na and subsequently 50 μl of formalin solution (2.5% was injected subcutaneously in the right paws after 1 h, 2 h and 3 h. The paw licking behavior was then evaluated in two phases. A dose of 20 mg/kg of pure diclofenac Na powder was determined as effective dose. Results: In the first phase, in term of reduced paw licking time, no significant differences were found in any of the groups compared to the control group. However, in the second phase, the animals which received pure drug powder and the physical mixture of diclofenac Na with Eudragit® RS100 showed significant differences at the first and second hours. In the animals received the nanoparticles and solid dispersion, significant differences were observed in the third hour compared to the control group. Conclusion: The analgesic effect of diclofenac Na could be improved by formulating its nanoparticles and solid dispersion with Eudragit® RS100. However, the nanoparticles revealed significantly higher analgesic effect than solid dispersion.
Lopes-Martins, R A B; Pegoraro, D H; Woisky, R; Penna, S C; Sertié, J A A
Petiveria alliacea L (Phytolaccaceae) is a perennial bush plant that grows widely in Brazil. The roots and leaves of P. alliacea have been used in folk medicine for their antispasmodic, sedative, diuretic and antihelminthic actions. We recently described the anti-inflammatory properties of P. alliacea administered topically and orally in different animal models. In the present study, we investigated the anti-inflammatory activity of a crude lyophilized extract of P. alliacea roots administered to rats with pleurisy. The oral administration of P. alliacea root extract did not significantly reduce the total number of leukocytes at the doses tested. By contrast, the highest dose of extract tested (43.9 mg/kg body wt.) significantly reduced the number of migrating neutrophils, mononuclear cells and eosinophils; the dose of 31.4 mg/kg body wt. also reduced mononuclear cell migration. The P. alliacea root extract also showed a significant analgesic effect in the experimental model used. The results of this study provide a basis for the use of P. alliacea extracts in popular folk medicine, but further studies are necessary to elucidate the mechanism of its anti-inflammatory and analgesic actions.
Aziza M Hussain
Full Text Available Background: Evidence regarding gender affecting the response to pain and its treatment is inconsistent in literature. The objective of this prospective, observational study was to determine the effect of gender on pain perception and postoperative analgesic consumption in patients undergoing laparoscopic cholecystectomy. Materials and Methods: We recruited 60 male and 60 female patients undergoing elective laparoscopic cholecystectomy. Patients were observed for additional intraoperative and postoperative analgesia. Numerical rating scale was documented at 10 min interval for 1 h in post-anesthesia recovery room and at 4, 8, and 12 h postoperatively. Boluses of tramadol given as rescue analgesia were also noted. There were no dropouts. Results: The mean pain scores were significantly higher in female patients at 20 and 30 min following surgery. Mean dose of tramadol consumption was significantly higher in female patients for the first postoperative hour (P = 0.002, but not in the later period. Conclusion: Female patients exhibited greater intensity of pain and required higher doses of analgesics compared to males in in the immediate postoperative period in order to achieve a similar degree of analgesia.
Sousa, Angela Maria; Ashmawi, Hazem Adel
Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200 μg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Sousa, Angela Maria; Ashmawi, Hazem Adel
Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200μg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60min after incision. Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.
The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889
Hossain, Ahamed Ismail; Faisal, Mohammad; Rahman, Shahnaz; Jahan, Rownak; Rahmatullah, Mohammed
Alternanthera sessilis is used by folk medicinal practitioners of Bangladesh for alleviation of severe pain. The objective of this study was to scientifically analyze the analgesic (non-narcotic) property of aerial parts of the plant along with antihyperglycemic activity. Antihyperglycemic activity was measured by oral glucose tolerance tests. Analgesic (non-narcotic) activity was determined by observed decreases in abdominal writhings in intraperitoneally administered acetic acid-induced pain model in mice. Administration of methanol extract of aerial parts led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. At doses of 50, 100, 200 and 400 mg per kg body weight, the extract reduced blood sugar levels by 22.9, 30.7, 45.4 and 46.1%, respectively compared to control animals. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg body weight, reduced blood glucose level by 48.9%. In analgesic activity tests, the extract at the above four doses reduced the number of abdominal writhings by 27.6, 37.9, 41.4, and 44.8%, respectively. A standard analgesic drug, aspirin, reduced the number of writhings by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400 mg per kg body weight. The results validate the folk medicinal use of the plant to alleviate pain. At the same time, the antihyperglycemic activity result suggests that the plant may be a potential source for blood sugar lowering drug(s).
Carr, D J; Gerak, L R; France, C P
A study was undertaken to investigate the relationship between morphine-induced analgesia and immunosuppression after acute administration. In male CD1 mice, morphine (10.0-100.0 mg/kg s.c.) produced a U-shaped immunosuppressive dose-effect curve on splenic natural killer (NK) activity. Morphine also induced dose-related analgesia, as measured by an increase in tail-flick latency during thermal application; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). In addition, morphine-induced suppression of splenic NK activity was antagonized in a dose-dependent manner and, at one dose of naltrexone (10.0 mg/kg), splenic NK activity was augmented. To investigate further the relationship between naltrexone antagonism of morphine-induced analgesia and immunomodulation, single doses of morphine (10.0-100.0 mg/kg) were administered to mice pretreated with naltrexone (0.01-10.0 mg/kg) or saline. A dose of 10.0 mg/kg of morphine produced 35% of the maximal possible effect in the analgesia study and no immunosuppression, whereas a dose of 32.0 mg/kg produced a maximal analgesic effect and significant suppression of NK activity. Naltrexone blocked morphine-induced analgesia and immunosuppression in a dose-dependent fashion. Moreover, the combination of 1.0 mg/kg of naltrexone and 32.0 mg/kg of morphine elevated splenic NK activity. A large dose of morphine (100.0 mg/kg) elicited full analgesia and had no effect on splenic NK activity in saline- or naltrexone-pretreated mice. Collectively, these results support the view that, in mice, morphine-induced analgesia and immunosuppression are mediated through a common opioid receptor type.
Hohlfeld, T; Zimmermann, N; Weber, A-A; Jessen, G; Weber, H; Schrör, K; Höltje, H-D; Ebel, R
Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1). We studied whether dipyrone, which has recently been reported to inhibit COX isoforms by a mechanism different from conventional non-steroidal anti-inflammatory drugs (NSAIDs), also interferes with the antiplatelet effect of aspirin. Arachidonic acid- and collagen-induced aggregation, as well as thromboxane formation, were measured in human platelet-rich plasma. Platelet P-selectin expression was determined by flow cytometry and cell-free COX enzyme activity was quantified by luminol-enhanced luminescence of human platelet microsomes. In addition, computerized docking was performed based on the crystal structure of COX-1. 4-Methylaminoantipyrine (MAA), the active metabolite of dipyrone, largely attenuated or even completely abolished the inhibition of arachidonic acid-induced platelet aggregation, thromboxane formation and P-selectin expression by aspirin. Similar results were obtained for other pyrazolinones, as well as for the conventional NSAIDs ibuprofen and naproxen. Moreover, MAA attenuated the effect of aspirin on COX activity of platelet microsomes, suggesting a competition with aspirin at the COX-1 enzyme. This was confirmed by docking studies, which revealed that MAA forms a strong hydrogen bond with serine 530 within the COX-1, thereby preventing enzyme acetylation by aspirin. This study demonstrates for the first time that dipyrone and other pyrazolinones have a high potential to attenuate or prevent the antiplatelet effect of aspirin. This should be considered if pyrazolinone analgesics are administered to patients with cardiovascular disease requiring antiplatelet aspirin therapy.
Porreca, Frank; Ossipov, Michael H
Gastrointestinal (GI) side effects such as nausea and vomiting are common following opioid analgesia and represent a significant cause of patient discomfort and treatment dissatisfaction. This review examines the mechanisms that produce these side effects, their impact on treatment outcomes in chronic pain patients, and counteractive strategies. A number of mechanisms by which opioids produce nausea and vomiting have been identified. These involve both central and peripheral sites including the vomiting center, chemoreceptor trigger zones, cerebral cortex, and the vestibular apparatus of the brain, as well as the GI tract itself. Nausea and vomiting have a negative impact on treatment efficacy and successful patient management because they limit the effective analgesic dosage that can be achieved and are frequently reported as the reason for discontinuation of opioid pain medication or missed doses. While various strategies such as antiemetic agents or opioid switching can be employed to control these side effects, neither option is ideal because they are not always effective and incur additional costs and inconvenience. Opioid-sparing analgesic agents may provide a further alternative to avoid nausea and vomiting due to their reduced reliance on mu-opioid signalling pathways to induce analgesia. Nausea and vomiting side effects limit the analgesic efficiency of current opioid therapies. There is a clear need for the development of improved opioid-based analgesics that mitigate these intolerable effects.
Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.
Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie
Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.
Jiang, Yu-Mao; Sun, Dan-Dan; Wang, Zhi-Guo; Li, Tao; Zhao, Xiao-Liang; Jiao, Yue; Liu, Yang; Li, Yu-Juan; Ouyang, Jing-Feng; Wang, Dan-Qiao
This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(PMCP-3(PMCP-3 in the spinal cord. Copyright© by the Chinese Pharmaceutical Association.
events related to analgesic use such as sedation and respiratory depression. It is therefore imperative to prevent and treat postoperative pain, but at the same time not to cause harm from ... to CO2, whereas both measurements were depressed for 3 hours ... vascular tissues and then finally to muscle and fat where it is.
Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q
Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, antihyperalgesic, and anti-inflammatory properties of melatonin using a validated burn injury (BI) model in healthy male volunteers...... by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal...... thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined...
Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg
, visual disturbances, and adverse reactions. Pain upon ambulation (visual analog scale, mean [95% confidence interval]) 24 hours after surgery in group A vs B vs C was as follows: 41 [37-46] vs 41 [36-45] vs 42 [37-47], P = 0.93. Sedation (numeric rating scale, median [range]) 6 hours after surgery......Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized......, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache...
Full Text Available Nour Mekkaoui,1 Imane Issef,1 Meryem Kabiri,1,2 Amina Barkat1,31Neonatology and Intensive Care Unit, National Reference Center in Neonatology and Nutrition, Children’s Hospital of Rabat, Rabat; 2CRECET, Faculty of Medicine and Pharmacy, Rabat; 3Research Team of Health and Nutrition, Faculty of Medicine and Pharmacy, Mohammed V University, Souissi, Rabat, MoroccoBackground: The aim of this study was to evaluate nondrug management practices concerning pain induced by blood sampling in newborns in a Moroccan neonatal unit and to determine whether the results reported from a randomized clinical study of nondrug analgesia could be reproduced in a routine care setting.Methods: Standardized prospective observation of analgesic practices used during blood sampling was performed. Pain was assessed using the Douleur Aiguë Nouveau-né (DAN, [Newborn Acute Pain] scale that incorporates facial expression, vocal expression, and limb movements of the newborn during realization of a painful procedure. Five different nondrug analgesic practices were investigated in 125 infants.Results: Median DAN scores for the five methods were 6 (1–10 for venous sampling with oral administration of 30% glucose, 5 (1–10 for venous sampling with sucking, 3 (0–6 for venous sampling with oral administration of 30% glucose combined with sucking, 4 (0–10 for venous sampling with oral administration of 30% glucose combined with sucking and administration of 2 mL of adapted infant formula, and 6 (3–8 for venous sampling with administration of 2 mL of adapted infant formula.Conclusion: Oral administration of 30% glucose combined with sucking provided better control of pain induced by blood sampling in newborns at our neonatal unit.Keywords: pain, neonate, assessment, 30% glucose, sucking
Full Text Available Objective: Essential oils are complex mixtures of chemical compounds, extracted from a wide range of plants. The volatile fraction of essential oils is responsible for their characteristic aroma and presents diverse biological properties that have been studied over the years. In Traditional Chinese Medicine, Piper nigrum is considered to be pungent and hot. Although its chemical constituents and respective pharmacological properties have been described by several authors, the volatile fraction is still underestimated as a therapeutic agent. The aim of this study was to evaluate the analgesic properties of the volatile fraction of Piper nigrum essential oil, in patients presenting different types of pain.
Prabhakar, K R; Veerapur, V P; Bansal, Punit; Vipan, K Parihar; Reddy, K M; Barik, Atanu; Reddy, Bharat Kumar D; Reddanna, P; Priyadarsini, K I; Unnikrishnan, M K
Treatment of phenols with ninhydrin in acidic medium afforded 2-hydroxy-2-(ortho-hydroxy-phenyl/naphthyl)-1,3-dioxoindanes, which being unstable were isolated in their hemiketal forms. These synthesized compounds were subjected to TLC screening for radical scavenging and in vitro lipoxgenase and cycloxygenase enzyme inhibition assays. The best compound was identified and studied in detail for steady-state and time-resolved free radical kinetics, viz., DPPH, ABTS(-), *OH and rate constants for these reactions were evaluated. The best compound was also subjected to in vivo anti-inflammatory and analgesic activities in which the compound showed good promise for further structural optimization.
Nørholt, Sven Erik; Hallmer, F; Hartlev, Jens
To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid).......To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid)....
Ishola, Ismail O; Agbaje, Esther O; Adeyemi, Olufunmilayo O; Shukla, Rakesh
The roots of Alafia barteri Oliver (Apocynaceae), Combretum mucronatum Schumach (Combretaceae) and Capparis thonningii Schum (Capparaceae) are used in Traditional African Medicine to alleviate painful and inflammatory conditions. This study investigated the analgesic and anti-inflammatory effects of the methanol root extracts of Alafia barteri (MeAB), C. mucronatum (MeCM), and Capparis thonningii (MeCT). Analgesic activity of the extracts (50, 100, and 200 mg/kg, p.o. 1 h) was evaluated using acetic acid-, formalin- and hot plate-induced pain while anti-inflammatory actions (100 or 200 mg/kg) were investigated using the carrageenan- and xylene-induced edema tests. MeAB, MeCM, and MeCT (200 mg/kg) inhibited acetic acid-induced abdominal constriction by 55.07, 46.67, and 47.25%, respectively. In the formalin test, the index of pain inhibition of early and late phases was, respectively, 47.83 and 81.98% for MeAB, 56.10 and 63.81% for MeCM, and 42.84 and 63.29% for MeCT (200 mg/kg). MeAB and MeCT pretreatments significantly increased the reaction time by 46.67 and 25.53%, respectively, 120 min post-treatment in the hot-plate test. Naloxone (5 mg/kg, s.c.) pretreatment 15 min before extract administration, significantly (p opioid pathway and/or inhibition of chemical mediators of pain and inflammation.
Full Text Available Objectives: Unlike most other Analgesic drugs, α2 adrenoceptor agonists are capable of producing analgesia. The aim of this study was to evaluate the Analgesic and antisympathetic effects of clonidine, an α2 adrenoceptor agonist in burn patients. Materials and Methods: This randomized, double-blind, placebo-controlled clinical trial performed on one hundred burn patients in Zarea Hospital, Mazandaran, Iran from august 2004 to July 2005. All patients divided in two groups. Case group (n=50 received oral clonidine, 3.3μg/kg TDS and controls (n=50 received placebo. Heart rate and systolic blood pressure and pain severity Visual analogue score (VAS, were recorded after clonidine administration. Statistical analysis was done by means of Mann Witney U test. Results: 50 patients (mean age 28.96±10 years in case group, and 50 patients (mean age 27.60±11.4 years in control group were studied. VAS pain scores and heart rate in the clonidine group were significantly lower than the control group (P< 0.0001, P< 0.02.there were no significant difference in systolic blood pressure between the two groups on the first and second day but on third day the systolic blood pressure in clonidine group, was lower than controls significantly (P=0.002. Conclusion: This study demonstrates that the use of oral clonidine affects the hemodynamic response to pain in burn patients. Our study demonstrated that clonidine can produce good analgesia and decreased in sympathetic over activity in burn patients, and also reduce opioid dose requirements.
Tammisto, T; Tigerstedt, I
1 The intensity of postoperative pain is influenced by many factors, for example, individual variation, site of incision and type of operation, anaesthetic technique, and the interval from the end of operation to the appearance of pain. 2 These factors affect the efficacy of analgesics. 3 Mild analgesics provide adequate pain relief in half of our patients in the immediate postoperative phase when the pain is slight to moderate. 4 The maximum effect of mild analgesics corresponds to that produced by morphine 6-10 mg. Adequate analgesia may not therefore be provided for the treatment of severe postoperative pain unless narcotic analgesics have been used peroperatively. 5 When mild analgesics are combined with narcotics synergism is achieved. 6 As postoperative pain decreases with time, mild analgesics usually provide adequate pain relief on the first and following postoperative days.
Otto, Marit; Bach, Flemming W; Jensen, Troels S
Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients...
Graversen, C.; Olesen, S.S.; Olesen, A.E.; Steimle, K.; Farina, D.; Wilder-Smith, O.H.G.; Bouwense, S.A.W.; Goor, H. van; Drewes, A.M.
AIM: To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain. METHODS: This was a double-blind, placebo-controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing
Full Text Available Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE and xylopic acid (XA, in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests, thermal (Tail-flick and Hargreaves thermal hyperalgesia tests, and mechanical (Randall-Selitto paw pressure test pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg -1 , p.o. and XA (10-100 mg kg -1 , p.o. inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory, thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg -1 , i.p. and diclofenac (1-10 mg kg -1 , i.p., used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.
Malver, Lasse Paludan; Brokjaer, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr
To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. © 2013 The British Pharmacological Society.
Heiskanen, Tarja; Kalso, Eija
Opioids are increasingly used to manage not only acute but also chronic pain and heroine addiction. These patients usually receive many other medications that can interfere with the effects of opioids and vice versa. Patients often need combinations of drugs for their pain management, for treating opioid-related adverse effects or for other indications including depression and anxiety. Several antibiotics can also have interactions with opioids. It is important to understand what potential interactions exist between opioids and other drugs. Drug interactions can occur due to pharmacokinetic interactions including effects of absorption, metabolic pathways, drug transport through membranes and protein binding. Our knowledge of the metabolism of opioids has significantly increased over the last years and it is now possible to appreciate the role CYP enzymes, mainly CYP 2D6 and 3A4/5, in the metabolism of many commonly used opioids like codeine and oxycodone. Our knowledge regarding the role of the transporter proteins in drug interactions related to opioids is unfortunately meagre. Opioids inhibit the gastrointestinal system and can thus change the absorption of other drugs. Opioids can have synergistic or additive interactions with other drugs that have analgesic or sedative effects. Endogenous opioids control many physiological functions and exogenous opioids can have effects on all important transmitter systems (cholinergic, GABAergic, dopaminergic and serotonergic). The literature in this field is mainly based on case reports. Interindividual differences play an important role. Other potential interactions include prolongation of the QT-interval and lowering of the threshold for convulsions.
McNaughton, Emily C; Black, Ryan A; Weber, Sarah E; Butler, Stephen F
Research on substance abusers in treatment suggests that tapentadol, a prescription analgesic, may have relatively low abuse potential. Messages posted by recreational drug abusers on online forums were examined for amount of discussion and endorsement for abuse of tapentadol and comparator drugs. Internet messages posted between January 1, 2011 and September 30, 2012 on seven drug-abuse web forums were evaluated. Proportions of posts and unique authors discussing tapentadol were compared with eight comparator compounds. Postcontent was coded to compare endorsement for abuse of tapentadol with two comparators, one drug with high desirability for abuse and one with low desirability for abuse. A total of 1,940,121 messages posted during the study period were copied from selected web forums. The proportion of all posts discussing tapentadol (proportion = 0.0003) was significantly lower than any of the comparator compounds (range of odds ratios from 16.6 to 104.3; P tapentadol, which was significantly lower than the highly desirable for abuse oxymorphone (ERo = 5.08; P = 0.0011) and was as low as tramadol (ERo = 1.66), which has a long-established profile of low abuse and desirability for abuse. Recreational abusers posting on web forums appear to be less interested in abusing tapentadol when compared with other, selected prescription analgesics based on the amount of discussion (i.e., fewer posts and authors mentioning tapentadol). Endorsement of the product for abuse was also low. Wiley Periodicals, Inc.
Full Text Available Stephanie Anderson1,2, Hollis Krug1,2, Christopher Dorman1, Pari McGarraugh1, Sandra Frizelle1, Maren Mahowald1,21Rheumatology Section, Veteran’s Affairs Medical Center, Minneapolis, Minnesota; 2Division of Rheumatology and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, Minnesota, USAObjective: To evaluate the analgesic effectiveness of intra-articular botulinum toxin Type B (BoNT/B in a murine model of chronic degenerative arthritis pain.Methods and materials: Chronic arthritis was produced in adult C57Bl6 mice by intra-articular injection of Type IV collagenase into the left knee. Following induction of arthritis, the treatment group received intra-articular BoNT/B. Arthritic control groups were treated with intra-articular normal saline or sham injections. Pain behavior testing was performed prior to arthritis, after induction of arthritis, and following treatments. Pain behavior measures included analysis of gait impairment (spontaneous pain behavior and joint tenderness evaluation (evoked pain response. Strength was measured as ability to grasp and cling.Results: Visual gait analysis showed significant impairment of gait in arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a substantial articular analgesic effect. Joint tenderness, measured with evoked pain response scores, increased with arthritis induction and decreased 49.5% after intra-articular BoNT/B treatment. No improvement in visual gait scores or decrease in evoked pain response scores were found in the control groups receiving intra-articular normal saline or sham injections. Intra-articular BoNT/B was safe, and no systemic effects or limb weakness was noted.Conclusions: This study is the first report of intra-articular BoNT/B for analgesia in a murine model of arthritis pain. The results of this study validate prior work using intra-articular neurotoxins in murine models. Our findings show chronic degenerative arthritis
Tamarova, Z A; Lymans'kyĭ, Iu P; Kostiuk, O I; Mitruzaeva, V A; Lymans'ka, L I
In experiments on mice of lines C57BL/6J and CBA/CaLac, the possibility of strengthening of analgesic effect of corvitin by the action of red polarized light (PL) on the acupoint (AP) E-36 was studied. The pain behavioral response (licking of the painful area) was caused by injection of 5% formalin in hind limb (0.25 microl subcutaneously). The duration of pain response was studied before and after systemic introduction of corvitin (10 mg/kg, intraperitoneal) or joint use of corvitin and red PL (10 minute session). It is established, that after application of red PL on the antinociceptive AP E-36 in all animals an authentic strengthening of antinociceptive effect of corvitin takes place. In C57BL/6J mice, application of corvitin alone weakened the pain response by 29.7% and during combined use of red PL and corvitin, it grew up to 53.1%. Mice of line CBA/CaLac were less sensitive both to corvitin, and PL. In this line, corvitin used alone reduced the duration of pain response by 14%, and by 32.4% during combined use with red PL. Non-traumatic, without side effects, the method of influence by low-intensive PL can be recommended to patients accepting corvitin for strengthening its efficiency.
Tigerstedt, I; Tammisto, T; Leander, P
The analgesic dose-effect relationship of nefopam was compared in a double-blind randomised trial with that of oxycodone in immediate postoperative pain. Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v. (maximum six times) to patients in pain after upper abdominal surgery until their wound pain (scored 0-3) disappeared. The mean pain intensity (PI), initially 2.2 in both groups, descreased by approximately the same extent for up to two doses in both groups (to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg). Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose (24 mg). In the nefopam group, the PI score fell to 1.1 after the fourth dose (60 mg). This seemed to be the "ceiling" effect since additional doses up to 90 mg did not result in greater pain relief. In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone. In the nefopam group, 12 patients (75%) needed further pain relief after the maximal dosage (6 x 15 mg). In these patients, oxycodone (maximally 16 mg) gave satisfactory analgesia. Drowsiness and a decrease in the respiratory rate were the principal side-effects of oxycodone, whereas tachycardia, restlessness, sweating and nausea were more frequent after nefopam.
Prozialeck, Walter C; Jivan, Jateen K; Andurkar, Shridhar V
Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.
Zhou, You-Long; Liu, Yi-Jun; Chen, Jian-Hui; Hu, Bin; Zhang, Shi-Qing; Sun, Guo-Sheng
To search for an effective therapy for the nerve root pain caused by prolapse of lumbar intervertebral disc. One hundred and ninety-two cases were randomly divided into a Huaisanzhen group of 96 cases, a drug control group of 48 cases and an acupuncture control group of 48 cases. The Huaisanzhen group were treated by Huaisanzhen therapy, the drug control group by intramuscular injection of aspirin-DL-lysine and the acupuncture control group by routine acupuncture. The time inducing analgesic effect was shorter, the effect-lasting time was longer, and the analgesic effect and the comprehensive therapeutic effect were better in the treatment group as compared with the two control groups with very significant differences (P prolapse of lumbar intervertebral disc.
Dewan Roshan Singh
Full Text Available Tapentadol is a novel, centrally acting analgesic with dual mechanism of action, combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in the same molecule. It has an improved side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic pain.
Singh, Dewan Roshan; Nag, Kusha; Shetti, Akshaya N.; Krishnaveni, N.
Tapentadol is a novel, centrally acting analgesic with dual mechanism of action, combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in the same molecule. It has an improved side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic pain. PMID:24015138
Mani, Vasudevan; Ramasamy, Kalavathy; Abdul Majeed, Abu Bakar
The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavour that they impart. In the present study, the effect of the total alkaloidal extract from Murraya koenigii leaves (MKA) with respect to anti-inflammatory, analgesic and anti-ulcerogenic effects were evaluated using different experimental animal models. Oral supplementation of MKA at 10, 20 and 40 mg kg(-1) body weight successfully and dose-dependently reduced the formation of oedema induced by carrageenan, histamine and serotonin as well as formaldehyde-induced arthritis. In addition, the extract (10, 20 and 40 mg kg(-1), p.o.) attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by a subplantar injection of formalin in mice. MKA at higher doses (20 and 40 mg kg(-1), p.o) reduced the early phase response induced by formalin as well as reaction time on hot plate models. Interestingly, there was no ulcer score with the ulcerogenic effect of MKA. Moreover, all the doses of MKA (10, 20 and 40 mg kg(-1), p.o) showed promising anti-ulcerogenic activity with protection against acute gastric ulcers induced by ethanol plus hydrochloric acid and aspirin models in a dose dependent manner.
Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M
The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. Copyright © 2013 Elsevier Ltd. All rights reserved.
José Leonardo Simone
Full Text Available The objective of the study was to compare the analgesic effectiveness of dexamethasone and diclofenac sodium administered preemptively after surgical removal of third molars. Forty-four ASA (American Society of Anesthesiologists I patients (19 men, 35 women; 16–28 years old randomly and double-blindly received diclofenac sodium (50 mg or dexamethasone (8 mg or placebo 1 h before surgery. Intensity of pain, measured with a visual analog scale (VAS, was the variable studied at different postoperative times (1 h, 2 h, 3 h, 6 h, 8 h, 12 h, 48 h, 4 d and 7 d. The total amount of rescue medication (TARM ingested (paracetamol was another variable of the study. The Kruskal-Wallis statistical test was used. A p value of < .05 was adopted to reject the null hypothesis. The dexamethasone group showed lower pain intensity (p < .05 than the diclofenac sodium and placebo groups (p < .05. No difference in TARM was observed among the groups (p < .05. Preemptively administered, dexamethasone was effective in controlling postoperative pain.
Chen, Fu-Feng; Huo, Fu-Quan; Xiong, Hui; Wan, Qing; Zheng, Ya-Nan; Du, Wen-Jie; Mei, Zhi-Nan
Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (D. cochinchinensis). The active components of total flavonoids from SD (SDF) have analgesic effect. The aim of this study is to evaluate the analgesic effects and potential mechanism of SDF on mechanical hypersensitivity induced by spared nerve injury (SNI) model of neuropathic pain in the rat. SNI model in rats was established and then the rats were treated with SDF intragastric administration for 14 days. Paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and days 1, 3, 5, 7, 9, 11, 14 after operation, respectively. After 14 days, we measured the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in the spinal dorsal horn. In addition, the expression of fibroblast growth factor receptor 3 (FGFR3), phosphorylated cyclic AMP response element-binding protein (p-CREB) and glial fibrillary acidic protein (GFAP) of the spinal dorsal horn was evaluated by western blotting and an immunofluorescence histochemical method, respectively. Intragastric administration of SDF (100, 200, 400 mg/kg) alleviated significantly SNI-induced mechanical hypersensitivity, as PMWT increased in a dose-dependent manner. Moreover, SDF not only reduced the level of NO, NOS, TNF-α and IL-1β, but also upregulated the level of IL-10 in the spinal dorsal horn of SNI rats. At the same time, SDF (100, 200, 400 mg/kg) could inhibit the expression of FGFR3, GFAP and p-CREB in the spinal dorsal horn. SDF has potentially reduced mechanical hypersensitivity induced by SNI model of neuropathic pain which may be attributed to inhibition of astrocytic function (like release pro-inflammatory cytokines) and NO release as well as p-CREB activation in the spinal dorsal horn. Copyright © 2015 Elsevier GmbH. All
Kol, Emine; Alpar, Sule Ecevit; Erdoğan, Abdullah
The purpose of this study was to investigate the efficiency of preoperative pain management education and the role of analgesics administration before the onset of pain postoperatively. The study was a prospective, randomized, and single-blind clinical trial, which was conducted January 1, 2008 through October 1, 2008 in the Thoracic Surgery Unit of Akdeniz University Hospital. A total of 70 patients who underwent thoracotomy (35 in the control group and 35 in the study group) were included in the study. Of the patients, 70% (n = 49) were male and 30% (n = 21) were female. Mean age was 51 ± 10 years (range = 25-65). The same analgesia method was used for all patients; the same surgical team performed each operation. Methods, including preemptive analgesia and placement of pleural or thoracic catheter for using analgesics, that were likely to affect pain level, were not used. The same analgesia medication was used for both patient groups. But the study group, additionally, was educated on how to deal with pain preoperatively and on the pharmacological methods to be used after surgery. An intramuscular diclofenac Na 75 mg was administered to the study group regardless of whether or not they reported pain in the first two postoperative hours. The control group did not receive preoperative education, and analgesics were not administered to them unless they reported pain in the postoperative period. The routine analgesics protocol was as follows: diclofenac Na 75 mg (once a day) intramuscular administered upon the complaint of pain following extubation in the postoperative period and 20 mg mepederin intravenously (maximum dose, 100 mg/day), in addition, when the patient expressed pain. Pain severity was assessed during the second, fourth, eighth, 16th, 24th, and 48th hours, and marked using the Verbal Category Scale and the Behavioral Pain Assessment Scale. Additionally, the total dose of daily analgesics was calculated. The demographic characteristics showed a
Mario I. Ortiz
Full Text Available To the Editor Mardani-Kivi et al presented results about a triple blinded randomized controlled trial with gabapentin in patients that underwent anterior cruciate ligament (ACL reconstruction (1. In their manuscript, the introduction section is very illustrative about the subject. With respect to methodology, it is well known that the physical diagnosis of ACL injury is particularly difficult in several patients, and partial ACL tears are also difficult to diagnose on physical examination. In this particular case, how did the authors obtain the diagnosis of ACL in the patients? Likewise, ACL reconstruction can be delayed several weeks or months until the swelling has decreased and there is an appropriate range of motion. For this reason, I want to ask: was the cause of the ACL injury homogeneous in all patients?; was the time delay of the surgery the same for everyone; and was the type of damage the same for all participants? Meperidine is an opioid with analgesic effects. The American Pain Society and the Institute for Safe Medication Practice (ISMP do not recommend meperidine use as pain relieving medication or they recommend it only in very special cases and with many precautions during its administration (2, 3. What was the rationale of the authors choosing meperidine as analgesic drug? In this same sense, authors did not indicate in their manuscript whether meperidine was administered by oral, intramuscular or intravenous pathways or patient-controlled analgesia. The time schedule of meperidine administration was not indicate in the manuscript; was meperidine administered q4h or q6h? How many doses were received by patients? I think it was a mistake to publish the demographic data of all patients (n=114. You had to eliminate the patients deleted in the presentation of the demographic characteristics of the patients (n=108, that is more correct. Table 2 and 3 were poorly prepared. Table 2 has missing data about the results at 24 hours in the
Preet Amol Singh
Full Text Available Objective: To evaluate the in vivo anti-inflammatory and analgesic potential of stem bark extract of Dillenia indica f. elongata (Miq. Miq. (D. indica f. elongata and its comparison with Shorea robusta Gaertn. (S. robusta and respective standard drugs in experimental animals. Methods: Analgesic models (hot plate, tail flick and formalin induced paw licking along with acute (carrageenan-induced and chronic (formalin-induced models of inflammation were evaluated for analgesic and anti-inflammatory potential of the plant extracts. Results: The results of the study showed that the ethyl acetate extracts of D. indica f. elongata (100 and 300 mg/kg and S. robusta (100 and 300 mg/kg possessed good central as well as peripheral analgesic activity as compared with pentazocine and indomethacin (10 mg/kg respectively. The extracts showed significant (P < 0.01 activity in carrageenan- and formalininduced chronic inflammation models by using indomethacin (8 mg/kg and diclofenac (13.5 mg/kg as standard drugs respectively. Conclusions: It can be concluded that the presence of major constituents like flavonoids, tannins and phenols in the ethyl acetate extracts of stem bark of D. indica f. elongata (100 and 300 mg/kg and S. robusta (100 and 300 mg/kg may be responsible for its analgesic and antiinflammatory activity.
Bashir, Samra; Gilani, Anwar H
Commercially available Aztec marigold (Tagetes erecta) flower extract (Af.Cr) was evaluated for the in vitro antioxidant activity and in vivo analgesic effect on acetic-acid-induced abdominal writhing. The results revealed the presence of pronounced antioxidant potential in Aztec marigold flowers and a dose-dependent (100 and 300 mg/kg) analgesic effect. The antioxidant and analgesic activities obtained seem to be in good accordance with the medicinal uses of Aztec marigold as an anti-inflammatory and analgesic. (c) 2008 John Wiley & Sons, Ltd.
Maione, Sabatino; Radanova, Lilyana; De Gregorio, Danilo; Luongo, Livio; De Petrocellis, Luciano; Di Marzo, Vincenzo; Imming, Peter
The molecular mechanism of action of dipyrone, a widely used antipyretic and non-opioid analgesic drug, is still not fully understood. Actions upon peripheral inflamed tissues as well as the central nervous system, especially upon the PAG-RVM axis, have been suggested. Dipyrone is a prodrug and its activity is due to its immediate conversion to its active metabolites. We tested the effect of two recently discovered metabolites of dipyrone, the arachidonoyl amides of 4-methylaminoantipyrine and 4-aminoantipyrine, on the neurons of the rostral ventromedial medulla (RVM), which are part of the descending pathway of antinociception. These compounds reduced the activity of ON-cells and increased the activity of OFF-cells. Both CB1 and TRPV1 blockade reversed these effects, suggesting that the endocannabinoid/endovanilloid system takes part in the analgesic effects of dipyrone. Copyright © 2015. Published by Elsevier B.V.
Borckardt, Jeffrey J; Reeves, Scott T; Frohman, Heather; Madan, Alok; Jensen, Mark P; Patterson, David; Barth, Kelly; Smith, A Richard; Gracely, Richard; George, Mark S
The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain, stress, and learned helplessness. Although the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as modulating pain, little is known about whether TMS over this area may affect perceived controllability. The present study explored the immediate effects of fast TMS over the left dorsolateral prefrontal cortex on the analgesic effects of perceived pain controllability. Twenty-four healthy volunteers underwent a laboratory pain task designed to manipulate perception of pain controllability. Real TMS, compared with sham, suppressed the analgesic benefits of perceived control on the emotional dimension of pain, but not the sensory/discriminatory dimension. Findings suggest that, at least acutely, fast TMS over the left dorsolateral prefrontal cortex may interrupt the perceived-controllability effect on the emotional dimension of pain experience. Although it is not clear whether this cortical area is directly involved with modulating perceived controllability or whether downstream effects are responsible for the present findings, it appears possible that left dorsolateral prefrontal TMS may produce analgesic effects by acting through a cortical perceived-control circuit regulating limbic and brainstem areas of the pain circuit. Despite evidence that prefrontal TMS can have analgesic effects, fast left prefrontal TMS appears to acutely suppress analgesia associated with perceived-control. This effect may be limited to the emotional dimension of pain experience. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
E S Adarsh
Full Text Available Background: Opioid analgesics used for analgesia are associated with sedation, respiratory depression and post-operative nausea and vomiting. Non-steroidal anti-inflammatory drugs such as diclofenac are a safe and effective alternative with opioid-sparing effect. Objective: To evaluate the effectiveness of pre-operative rectal diclofenac suppository (1 mg/kg in cleft palate repair for post-operative analgesia and reduction in post-operative opioid requirements. Study Design: A randomized clinical trial. Methods: After obtaining approval from the institutional ethical committee, 60 children were allocated by a computer-generated randomisation into two groups of 30 each; group D (Diclofenac group and group C (Conventional group. Children in group D and group C were similar in all aspects except for the fact that group D children received 1 mg/kg diclofenac suppository after induction. Pain was evaluated using modification of the objective pain scale by Hannallah and colleagues for 6 h post-operatively by an anaesthesiology resident or nursing staff who was blinded to the group. If the pain score was more than 3, rescue analgesic I.V. fentanyl 0.5 μgm/kg was administered. The pain scores at different intervals, number of doses and quantity of rescue analgesic required were noted. Results: We observed that pre-operative rectal diclofenac provided effective analgesia in the immediate post-operative period, as evidenced by reduced pain scores and reduced opioid requirement (P=0.00002. There was no evidence of any increased perioperative bleeding in the diclofenac group. Conclusion: Pre-operative rectal diclofenac reduces opioid consumption and provides good post-operative analgesia.
Su, Shulan; Hua, Yongqing; Wang, Yanyan; Gu, Wei; Zhou, Wei; Duan, Jin-ao; Jiang, Haifeng; Chen, Ting; Tang, Yuping
The Chinese herbs of myrrh and frankincense are often combined for treating some inflammatory pain diseases with synergistic therapeutic effects. In this study, we investigated the effects of individual herbal extracts and combined extract on anti-inflammatory and analgesic activities in vivo and analyzed the potential bioactive components from the combination extract by ultra-performance liquid chromatography coupled with mass spectrum (UPLC-MS/MS). The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin and carrageenan. In addition, we determined the levels of PGE(2) and nitrite in the edema paw. The analgesic activity was examined against oxytocin-induced dysmenorrhea in mice. The effects of the administration of dolantin or indomethacin were also studied for references. The components in combination extract (CWE) were analyzed by UPLC-MS/MS. The results showed that myrrh water extract (MWE) and the combined extract (CWE) at the 3.9 g/kg, and 5.2 g/kg showed inhibition of formalin-induced paw edema with inhibition rate of 30.44%, and 23.50%, respectively. The PGE(2) production was inhibited significantly by all samples (P<0.01 or P<0.05). CWE showed stronger suppression on carrageenan-induced mice paw edema at 2 and 3h after administration of drugs. The inhibitory effect of CWE on nitrite production was between that of MWE and water extract of frankincense (FWE) at 5.2 g/kg. The dysmenorrhea mice test showed MWE could remarkably reduce the writhing times (P<0.05) and prolong the latency period, while FWE showed no obvious effects on the writhing times. CWE significantly reduced the writhing times and prolong the latency period (P<0.01). These results demonstrated MWE, FWE, and CWE exhibited significant anti-inflammatory and analgesic activities. The findings suggest that CWE may be therapeutically more useful for mitigating inflammatory pain than individual herbal extract. In addition, 12 potential active compounds
Giordano, Tatiana; Steagall, Paulo V M; Ferreira, Tatiana H; Minto, Bruno W; de Sá Lorena, Sílvia Elaine Rodolfo; Brondani, Juliana; Luna, Stelio P L
To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy. Randomized, prospective and blinded clinical trial. 100 female cats. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.
Schmidt-Rondon, Eric; Wang, Zhenping; Malkmus, Shelle A; Di Nardo, Anna; Hildebrand, Keith; Page, Linda; Yaksh, Tony L
Mast cell (MC) degranulation has been implicated in the side effect profile of a variety of clinically useful agents. Thus, after intrathecal delivery, formation of space-occupying, meningeally-derived masses may be related to local MC degranulation. We systematically characterized degranulating effects of opioid and nonopioid analgesics on cutaneous flares in the dog and in primary human MC (hMC) cultures. Dogs were anesthetized with IV propofol and received intradermal (ID) injections (50μL). Flare diameters were measured at 30min. Drugs showing flare responses were tested after intramuscular (IM) cromolyn (10mg/kg), a MC stabilizer. Human primary MCs (human cord blood CD34+/CD45+ cells) were employed and β-hexosaminidase in cell-free supernatants were measured to assess degranulation. A significant skin flare for several classes of agents was observed including opioids, ziconotide, ketamine, ST-91, neostigmine, adenosine, bupivacaine, lidocaine, MK-801 and 48/80. Tizanidine, fentanyl, alfentanil, gabapentin and baclofen produced no flare. Flare produced by all ID agents, except adenosine, bupivacaine and lidocaine, was reduced by cromolyn. Naloxone had no effect upon opiate or 48/80 evoked flares. In hMC studies, 48/80 resulted in a concentration-dependent release of β-hexosaminidase. The rank order of drug-induced hMC β-hexosaminidase release was similar to that for flares. A variety of therapeutically useful drugs degranulate MCs. This action may account for side effects such as the intrathecal granuloma resulting from spinally-delivered opioids. This degranulating effect may be useful in predicting potential intrathecal toxicity in the development of novel agents. Copyright © 2017. Published by Elsevier Inc.
Choi, Soo Joo; Kim, Myung Hee; Jeong, Hui Yeon; Lee, Jeong Jin
Perioperative lidocaine infusion improves postoperative outcomes, mostly after abdominal and urologic surgeries. Knowledge of the effect of lidocaine on peripheral surgeries is limited. Presently, we investigated whether intraoperative lidocaine infusion reduced anesthetic consumption, duration of ileus, pain intensity, analgesic consumption and hospital stay after breast plastic surgeries. Sixty female patients, aged 20-60 years, enrolled in this prospective study were randomly and equally divided to two groups. One group (n = 30) received a 1.5 mg/kg bolus of lidocaine approximately 30 min before incision followed by continuous infusion of lidocaine (1.5 mg/kg/h) until skin closure (lidocaine group). The other group (n = 30) was untreated (control group). Balanced inhalation (sevoflurane) anesthesia and multimodal postoperative analgesia were standardized. End tidal sevoflurane concentration during surgery, time to the first flatus and defecation, visual analog pain scale (0-10), analgesic consumption and associated side effects at 24, 48, and 72 h after surgery, hospital stay, and patient's general satisfaction were assessed. Compared to the control group, intraoperative lidocaine infusion reduced by 5% the amount of sevoflurane required at similar bispectral index (P = 0.014). However, there were no significant effects of lidocaine regarding the return of bowel function, postoperative pain intensity, analgesic sparing and side effects at all time points, hospital stay, and level of patient's satisfaction for pain control. Low dose intraoperative lidocaine infusion offered no beneficial effects on return of bowel function, opioid sparing, pain intensity and hospital stay after various breast plastic surgeries.
Enomoto, Hiroyuki; Fujikoshi, Shinji; Funai, Jumpei; Sasaki, Nao; Ossipov, Michael H; Tsuji, Toshinaga; Alev, Levent; Ushida, Takahiro
Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP). Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials. Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP. The primary outcome measure for pain was the Brief Pain Inventory, average pain score. A secondary outcome measure, the Beck Depression Inventory-II, was used for depressive symptoms. The changes in score from baseline to endpoint were determined for each index. Path analyses were employed to calculate the proportion of analgesia that may be attributed to a direct effect of duloxetine on pain. A total of 851 patients (400 duloxetine and 451 placebo) were included in this analysis. Duloxetine significantly improved pain scores compared with placebo (p<0.001). It also significantly improved depressive scores compared with placebo (p=0.015). Path analyses showed that 91.1% of the analgesic effect of duloxetine could be attributed to a direct analgesic effect, and 8.9% to its antidepressant effect. Similar results were obtained when data were evaluated at weeks 4 and 7, and when patients were randomized to subgroups based on baseline pain scores, baseline depressive symptoms scores, and gender. Duloxetine significantly improved pain in patients with CLBP. Path analyses results suggest that duloxetine produced analgesia mainly through mechanisms directly impacting pain modulation rather than lifting depressive symptoms. This effect was consistent across all subgroups tested.
Elson A. Costa
Full Text Available Cheiloclinium cognatum (Hippocrateaceae has been used in folk medicine to treat fever and edema. In this paper, we report the anti-inflammatory and analgesic activities of the crude dichloromethane extract (DECc from C. cognatum root barks collected in Auguste de Saint Hilaire wood at Universidade Federal de Goiás. Doses of 0.1, 0.3 and 1.0 g/kg caused a dose-dependent inhibition of croton oil-induced ear edema in mice equivalent to 21, 30 and 51%, respectively. There was a significant increase in analgesic-meter-induced tail flick test equivalent to 105, 189 and 200% of increase tail flick reaction time. These results allowed to suggest that C. cognatum could be a source of new compounds which anti-inflammatory and analgesic activities.
Garza Villarreal, Eduardo A; Elvira Brattico; Lene Vase; Leif Østergaard; Peter Vuust
Listening to music has been found to reduce acute and chronic pain. The underlying mechanisms are poorly understood; however, emotion and cognitive mechanisms have been suggested to influence the analgesic effect of music. In this study we investigated the influence of familiarity, emotional and cognitive features, and cognitive style on music-induced analgesia. Forty-eight healthy participants were divided into three groups (empathizers, systemizers and balanced) and received acute pain indu...
Du, Kairong; Wang, Xue; Chi, Laiting; Li, Wenzhi
The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.
Full Text Available Abstract Background Pain and impaired mobility because of osteoarthritis (OA is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1 antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID, Tramadol - synthetic opiate, or Placebo for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. Results Acute hyperthermia developed after ABT-116 treatment (P P ≤ 0.01 and tramadol (P ≤ 0.001 led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01. Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P R ≥ ±0.40, P ≤ 0.005. Placebo treatment effects were evident with all variables studied. Conclusion Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying
Mogbojuri, Olufunke M; Adedapo, Adeolu A; Abatan, Matthew O
. tragacantha and indomethacin produced significant (p<0.05) inhibition of paw edema compared with the control using histamine and carrageenan methods of paw edema induction. There was significant (p<0.05) reduction in writhing movements at 100 mg/kg and 200 mg/kg of n-hexane, chloroform, and ethyl acetate leaf extracts of S. tragacantha and indomethacin (10 mg/kg) when compared to the control. This effect using tail flick test was not as effective when compared to the writhing test. The different leaf extracts of S. tragacantha exhibited anti-inflammatory and analgesic properties and they are also safe for medicinal use.
Full Text Available μ-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.
Full Text Available This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of glycine transporter 2 (GlyT2 in human GlyT2-expressing HEK293 cells and did not bind various major transporters or receptors of neurotransmitters in a competitive manner. Thus, GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. Intravenous, oral, and intrathecal injections of GT-0198 decreased the pain-related response in a model of neuropathic pain with partial sciatic nerve ligation. This result suggests that GT-0198 has an analgesic effect. The analgesic effect of GT-0198 was abolished by the intrathecal injection of strychnine, a glycine receptor antagonist. Therefore, GT-0198 is considered to exhibit its analgesic effect via the activation of a glycine receptor by glycine following presynaptic GlyT2 inhibition in the spinal cord. In summary, GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in vivo efficacy in behavioral models of neuropathic pain.
Lajili, Sirine; Deghrigue, Monia; Bel Haj Amor, Haifa; Muller, Christian D; Bouraoui, Abderrahman
Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities. This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/CH2Cl2 crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae). Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-α) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10-250 μg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200 mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200 mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200 mg/kg. Crude extract, F1 and F2 showed an interesting inhibition of TNF-α secretion with IC50 values of 25, 52 and 24 μg/mL, respectively, and a significant anti-inflammatory activity in vivo (p effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50 mg/kg. These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect.
Yimam, Mesfin; Lee, Young-Chul; Moore, Breanna; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Kim, Mi-Ran; Hyun, Eu-Jin; Chu, Min; Brownell, Lidia; Jia, Qi
Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema. A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively. Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.
Kim, Jong Chan; Byun, Sunghye; Kim, Seongsu; Lee, Seon-Yi; Lee, Joo Hyung; Ahn, Sowoon
Depending on the type of injury, the pain mechanisms are multifactorial. Preoperative pregabalin administrations as an adjunct to a multimodal postoperative pain management strategy have been tested in various surgical settings. The purpose of current study was to evaluate the effects of preoperative pregabalin administration on postoperative pain intensity and rescue analgesic requirement following video-assisted thoracoscopic surgery (VATS). Sixty adult patients undergoing VATS were randomly assigned either to receive pregabalin 150 mg (Pregabalin group) or placebo (Control group) 1 hour before anesthesia. Primary efficacy variable was pain intensity. Secondary efficacy variables were the requirement of rescue analgesics, total volume of intravenous patient-controlled analgesia (IV-PCA), and adverse effects induced by pregabalin or IV-PCA. Pain intensity scores at post-anesthesia care unit (PACU), 6 and 24 hours were lower significantly in the Pregabalin group compared with the Control group (mean [SD]; 5.6 [2.0] vs 6.8 [1.8]; mean difference: 1.2, 95% CI of difference: 0.2166-2.1835, P = .018, mean [SD]; 3.8 [1.9] vs 5.6 [1.4]; mean difference: 1.8, 95% CI of difference: 1.0074-2.7260, P = .001 and mean [SD]; 2.6 [1.6] vs 3.5 [1.5]; mean difference: 0.9, 95% CI of difference: 0.0946-1.7054, P = .029, respectively]. Also, the frequency of additional rescue drug administered at PACU (median [interquartile range]; 2 [2-3] vs 1 [1-2], P = .027) was significantly less in the Pregabalin group. The incidences of adverse effects related to pregabalin or IV-PCA were not different between the groups. A single administration of pregabalin 150 mg before VATS decreased postoperative pain scores and incidence of additional rescue analgesics in the immediate postoperative period without increased risk of adverse effects.
Bian, Zhao-Xiang; Zhang, Man; Han, Quan-Bin; Xu, Hong-Xi; Sung, Joseph J Y
To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms. JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method. NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg), as compared to that of NH rats (57.7 +/- 1.9 mmHg, P < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean DeltaAUC values were: 0.17 +/- 0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/- 0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and 0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared
Background: Ondansetron is used to reduce tramadol induced postoperative nausea and vomiting (PONV). Studies on patient-controlled analgesia (PCA) found that ondansetron reduces the analgesic efficacy of tramadol. Drug requirement in PCA and in conventional intravenous analgesia without PCA device may differ.
In this present study, the analgesic activity of the aqueous extract of the leaves of Dichrostachy cinerea was investigated in mice using acetic acid-induced writhing and hot plate test, while the anti-inflammatory activity was investigated in rats using the carrageenan and dextran- induced paw edema. The extract (400 ...
Kolaviron is a defatted ethanol extract from the seeds of Garcinia Kola. In the present study, the analgesic and anti-inflammatory properties of Kolaviron is investigated using both thermal and chemical models of pain assessment in mice and rats. Varying doses of Kolaviron were given 30 minutes prior to the induction of ...
Methanolic extract of leaves and soft stems of Erythrina variegata (EVLSS) was investigated for analgesic activity at the doses of 50, 100, 200 and 400 mg/kg body weight orally. All the doses of EVLSS significantly attenuated the writhing responses induced by intraperitoneal injection of acetic acid in mice.
Md. Sarwar Hossain
Full Text Available Objective: To examine the analgesic and anti-inflammatory activities of Xanthosoma sagittifolium L. (X. sagittifolium leaves. Methods: The fresh leaves of X. sagittifolium were extracted with methanol followed by fractionation using ethyl acetate fraction (EAF, n-hexane fraction, chloroform fraction and aqueous fraction. The analgesic activity was determined by acetic acid-induced writhing test and tail immersion test using Swiss albino male mice. Carrageenan-induced paw edema test was used to resolve the anti-inflammatory activity using Wistar albino male rats. Results: The results displayed that among these four samples, EAF had maximum analgesic efficacy (P < 0.001 measured by acetic acid-induced writhing test (71.37%. In case of tail immersion test, EAF also exerted maximum activity (5.03 s, P < 0.001 at 180 min compared to n-hexane fraction, chloroform fraction and aqueous fraction at maximum concentration. In case of anti-inflammatory test, EAF remained ascendancy in its activity (P < 0.001 and it inhibited 72.92% of paw edema at maximum concentration at 180 min with respect to remaining fractions. Conclusions: The above evidences suggest that EAF of X. sagittifolium leaves is a potential source of natural compounds having analgesic and anti-inflammatory activities.
Abdulkarim, Muthanna F; Abdullah, Ghassan Z; Chitneni, Mallikarjun; Salman, Ibrahim M; Ameer, Omar Z; Yam, Mun F; Mahdi, Elrashid S; Sattar, Munavvar A; Basri, Mahiran; Noor, Azmin M
During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery. A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel. After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae. The nanocream containing the newly synthesized POEs was successful for trans-dermal delivery of piroxicam.
Jadidi, Majid; Khatami, Mahfouzeh Sadat; Mohammad-Pour, Fatemeh; Bandavi, Afsaneh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Taherian, Abbas Ali; Miladi-Gorji, Hossein
This study examined the effects of low frequency magnetic field (MF) on tolerance to analgesic effect of morphine in rats. Rats were made tolerant to morphine by injecting morphine (10 mg/kg, s) once daily for 8 consecutive days. Rats were simultaneously exposed to an MF (50 Hz at 1, 50, and 100 μT for 30 min) before, immediately, or 30 min after injection of morphine, and also exposed to a 0.5, 6, 12, and 30 Hz at 100 μT for 30 min before injection of morphine. The percentage of maximum possible effect of morphine (% MPE) was measured on the 1st, 4th, and 8th days by hot plate test. We observed that MF radiation (50 Hz at 1 µT and 30 Hz at 100 µT) immediately before and MF radiation (50 Hz at 100 µT) after morphine injection prevented the development of morphine tolerance compared to control. Also, we found that exposure to MF (50 Hz at 1, 50, and 100 µT) 30 min after injection of morphine failed to maintain the analgesic effect of morphine. Our results showed that exposure to low frequency electromagnetic field (30 and 50 Hz) immediately before or after the injection of morphine may be a potential method for treating the development of morphine tolerance in rats. Bioelectromagnetics. 38:618-625, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Maĭsov, N I; Tolmacheva, N S
The effect of different groups of neurotropic substances was studied on labeled noradrenaline and gamma-aminobutyric acid (GABA) uptake by synaptosomes of the rat brain cortex. It has been shown that each group of the test compounds is characterized by specific qualitative and quantitative features of the action on the above processes. Thus, psychostimulants actively inhibit noradrenaline uptake without changing GABA uptake. On the contrary, neuroleptics exert a pronounced inhibitory effect on GABA uptake and insignificantly inhibit noradrenaline accumulation. Antidepressants are very potent while narcotic analgesic drugs are less potent inhibitors of the accumulation of both neuromediators. Morphine and nalorphine have no effect on these processes.
Full Text Available Background: Magnesium Sulfate (MgSO4 has been used as a pharmacologic agent in different situations for many years in the treatment of tachyarrhythmias, myocardial ischemia, preeclampsia, and tocolysis among others. The analgesic effect of MgSO4 for postoperative pain has been used since the 1990s. Postoperative pain is one of the most common complications in the perioperative period and can result in serious consequences in different organs if left untreated. Inguinal herniorrhaphy is among the most common surgeries and is almost always accompanied by severe pain. The object of this study is to determine the effect of a pre-induction infusion of MgSO4 on the reduction of postsurgical pain after herniorrhaphy. Methods: This double-blind, randomized clinical trial included 105 ASA class I and class II herniorrhaphy patients at Shariati Hospital in years 2004 and 2005. For statistical analysis, the 2 and T tests were used. The patients were divided into three groups based on block randomization. Patients in the following groups received: Group A, 200 ml of normal saline infusion (placebo; Group B, 25 mg/kg MgSO4 in 200 ml of normal saline; Group C, 50 mg/kg MgSO4 in 200 ml of normal saline. All groups were infused twenty minutes before induction of anesthesia using identical methods and dosage in all three groups. Heart rate and mean arterial pressure (MAP at pre- and postintubation and so at skin incision time were charted. Visual analog scale (VAS pain score, nausea, vomiting and the amount of morphine used before recovery room discharge and in six, twelve and twenty-four hours after recovery discharge was recorded. Results: The average age for the different groups was as follows: Group A: 33.6, Group B: 37.37, Group C: 32.74. Nausea and vomiting between the case and control groups were not statistically different (60% vs. 71.4%, p=0.0499, nor was the amount of Morphine used. On recovery room discharge, the VAS scores were 8.1, 7.2, and 5
Gao, Yong-Hui; Wang, Jun-Ying; Qiao, Li-Na; Chen, Shu-Ping; Tan, Lian-Hong; Xu, Qiu-Ling; Liu, Jun-Ling
anti-asialo-GM1 antibody, the increased thermal pain threshold following EA intervention was obviously reduced. Repeated EA interventions have a time-dependent cumulative analgesic effect in neuropathic pain rats, which is closely associated with its regulatory effects on NK cells, splenic IL-2, β-EP, and plasma IL-2, IL-1β, IFN-γ and TGF-β levels.
DEMİRKAYA, Kadriye; AKGÜN, Özlem Martı; ŞENEL, Buğra; ÖNCEL TORUN, Zeynep; SEYREK, Melik; LACİVİTA, Enza; LEOPOLDO, Marcello; DOĞRUL, Ahmet
ABSTRACT The most recently identified serotonin (5-HT) receptor is the 5-HT7 receptor. The antinociceptive effects of a 5-HT7 receptor agonist have been shown in neuropathic and inflammatory animal models of pain. A recent study demonstrated the functional expression of 5-HT7 receptors in the substantia gelatinosa (SG) of the trigeminal subnucleus caudalis, which receives and processes orofacial nociceptive inputs. Objective To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. Material and Methods Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 µl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0–12 min) and the late phase (Phase II: 12–30 min). Results LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. Conclusion Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain. PMID:27383702
Víctor Molina D.
Full Text Available Objective. To evaluate the pharmacological, clinical and toxicological effects of celecoxib and meloxicam for analgesia for 30 days in dogs with hip osteoarthritis. Materials and methods. Twenty-four patients were evaluated, 75% were females with an average age of 7.16 ± 2.06 years and twenty five percent were males with an average age of 7.83 ± 2.22 years. All patients had hip osteoarthritis and they were randomized into two groups; one group received oral celecoxib 5 mg/kg every 12 hours during one month and the second group received oral meloxicam 0.2 mg/kg every 24 hours during 1 month. The patients were evaluated for analgesia, and hematological, renal, liver, and coagulation tests on days 0, 10th and 30th after treatment initiation, and a gastric endoscopy on day 30. Statistical analysis was performed using a HSD Tukey test and c2 with a 5% level of statistical significance. Results. Both drugs reduced articular pain according to the Melbourne scale during the 30 days of treatment (p≤0.05. Hematological, renal, hepatic and coagulation tests were normal in both treatment groups. All patients presented chronic gastritis on endoscopy on day 30th. Conclusions. Both drugs decreased pain at day 30th without causing alterations in hematological, renal, hepatic or coagulation tests after 30 days of treatment. However, both drugs induced chronic gastritis.
Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza
Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery.
Wilsey, Barth L; Deutsch, Reena; Samara, Emil; Marcotte, Thomas D; Barnes, Allan J; Huestis, Marilyn A; Le, Danny
A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its nonpsychotropic metabolite, 11-nor-9-carboxy-THC, were related to percent change from baseline of several descriptors (eg, itching, burning, and deep pain). However, given the large number of multiple comparisons, false-discovery-rate-adjusted P-values were not significant. Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids. Such an appraisal of descriptors might contribute to the identification of distinct pathophysiologic mechanisms and, ultimately, the development of mechanism-based treatment approaches for neuropathic pain, a condition that remains difficult to treat. PMID:27621666
Conclusion: In our study, premedication with meperidine or no premedication was not associated with a reduction in abdominal pain during colonoscopy without sedation. The insertion time and cecal intubation rate showed no difference between patients with or without additional analgesic drugs prior to the procedure. However, as self-selection bias could not be ruled out, further randomized, placebo-controlled trials are needed to confirm our findings.
Ince, Ilker; Aksoy, Mehmet; Ahiskalioglu, Ali; Comez, Mehmet; Dostbil, Aysenur; Celik, Mine; Yilmaz, Ismayil; Mammadov, Renad; Dogan, Hasan; Boztok Ozgermen, Basak; Altuner, Durdu
This study investigated the effects of metamizole and paracetamol on pain and oxidative stress induced by scalpel incision and carrageenan in rats. Total of 144 rats were divided into groups of 12 animals. Six groups each were used for scalpel incision and carrageenan tests. Pain was inflicted by applying a scalpel incision or carrageenan. Pain-created groups by scalpel incision received metamizole (SIM) or paracetamol (SIP) at doses of 250 or 500 mg/kg. Pain-created groups by carrageenan received metamizole (CAM) or paracetamol (CAP) at doses of 250 or 500 mg/kg. Analgesic activity was determined by Basile Algesimeter. The COX-2 and MPO gene expressions were determined, and malondialdehyde and tGSH were measured in rat paws. In the scalpel incision test, pain was reduced in groups of SIM-250 and SIM-500 in the first hour by 65.2% and 91.3%, respectively, and in the third hour by 51.9% and 77.8%, respectively, compared with the SIC group. In SIP-250 and SIP-500 groups, pain was reduced in the first hour by 43% and 74%, respectively, and by 33.4% and 59.3%, respectively, in the third hour compared with the SIC group. In the carrageenan test, in groups CAM-250 and CAM-500, pain was reduced in the first hour by 72.3% and 86.1%, respectively, and by 65.8% and 71.4%, respectively, in the third hour compared with the CCG group. In groups CAP-250 and CAP-500, pain was reduced in the first hour by 52.8% and 69.4%, respectively, and by 28.6% and 25.8%, respectively, in the third hour compared with the CCG group. Metamizole inhibited COX-2 gene expression at a dose of 500 mg/kg in the carrageenan test. At doses of 250 and 500 mg/kg, metamizole reduced COX-2 and MPO gene expressions and oxidative stress induced by scalpel incision or carrageenan. But both doses of paracetamol were unable to suppress that parameters. Our results show that metamizole is more effective than paracetamol for treating surgical trauma-related pain, inflammation, and oxidative stress and hence may be
Lin, Chia-Shu; Wu, Shih-Yun; Wu, Long-Ting
Research on shared medical decision-making suggested that both the potency of a treatment and the probability of it being successful influence individual treatment preferences. Patients also need to consider the negative attributes of treatments, such as the occurrence of adverse effects or a slow start to the therapeutic effects. It remains unclear how these attributes influence individual treatment preferences. We investigated how the analgesic effect, the adverse effect, and the time-course effect influenced the preference of analgesic treatments. Forty-five healthy volunteers participated in three hypothetical analgesic decision-making tasks. They were instructed to imagine that they were experiencing pain and choose between two hypothetical analgesic treatments: the more potent radical treatment and the less potent conservative treatment. The potency of a treatment was countered by the following attributes: the probability of working successfully, the probability of inducing an adverse effect, and the time required for the treatment to reach its maximal effect. We found that (a) when the overall probability that a treatment would induce an adverse effect decreased, the participants changed their preference from a conservative treatment to a radical treatment; (b) when the time-course for a treatment to reach its maximal effect was shortened, the participants changed their preference from a conservative treatment to a radical treatment, and (c) individual differences in prior clinical pain and the degree of imagined pain relief were associated with preferences. The findings showed that the adverse effects and the time course of treatments guide the analgesic treatment preferences, highlighting the importance of sharing information about negative attributes of treatments in pain management. The findings imply that patients may over-emphasize the occurrence of adverse effect or a slow time-course of treatment effect. In terms of shared medical decision
Bedini, Andrea; Spampinato, Santi Mario
Chronic pain is a clinically relevant and yet unsolved conditions that is poorly treated with the currently available drugs, thus highlighting the urgent need of innovative analgesics. Although opiates are not very effective in the treatment of inflammatory and neuropathic pain, developing novel opioid receptor peptide agonists, as well as modulating the opioid receptor-mediated responses in a ligand-specific fashion, may represent an innovative and promising strategy to identify more efficacious and safer antalgic drugs. In this review, novel analogues of endomorphin 1 (a mu opioid receptor selective agonist able to induce analgesia in different animal models of pain - including neuropathic pain) and dermorphin (one of the most potent opioid peptide existing in nature) will be discussed as they are emerging as a promising starting point to develop novel opioid agonists: endomorphin 1 analogues, in fact, may determine antinociception in different models of neuropathic pain with reduced side effects as compared to classic opiates as morphine; dermorphin analogues may elicit analgesia in animal models of both inflammatory and neuropathic pain and with less severe adverse effects. Furthermore, such opioid peptides may allow to explore unprecedented modalities of ligand-receptor interactions, helping to characterize biased agonism at opioid receptors: exploiting functional selectivity at opioid receptor may lead to identify innovative analgesic with improved pharmacological responses and optimized side effects. Thus, innovative opioid peptides, as those outlined in this review, are promising candidates to develop more effective opioid analgesics to be employed as medications for chronic pain states, as inflammatory or neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Demirkaya, Kadriye; Akgün, Özlem Martı; Şenel, Buğra; Öncel Torun, Zeynep; Seyrek, Melik; Lacivita, Enza; Leopoldo, Marcello; Doğrul, Ahmet
To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 µl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0-12 min) and the late phase (Phase II: 12-30 min). LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain.
Toyama, Satoshi; Shimoyama, Naohito; Shimoyama, Megumi
Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN). Several chemotherapeutic agents used for the treatment of malignant diseases induce dose-limiting neuropathic pain that compromises patients' quality of life. Here, we examined the analgesic effect of orexin-A in a murine model of CIPN, and compared it with the effect of duloxetine, the only drug recommended for the treatment of CIPN pain in patients. CIPN was induced in male BALB/c mice by repeated intraperitoneal injection of oxaliplatin, a platinum chemotherapeutic agent used for the treatment of advanced colorectal cancer. Neuropathic mechanical allodynia was assessed by the von Frey test, and the effect on acute thermal pain was assessed by the tail flick test. Intracerebroventricularly administered orexin-A dose-dependently attenuated oxaliplatin-induced mechanical allodynia and increased tail flick latencies. Oxaliplatin-induced mechanical allodynia was completely reversed by orexin-A at a low dose that did not increase tail flick latency. Duloxetine only partially reversed mechanical allodynia and had no effect on tail flick latency. The analgesic effect of orexin-A on oxaliplatin-induced mechanical allodynia was completely antagonized by prior intraperitoneal injection of SB-408124 (orexin type-1 receptor antagonist), but not by prior intraperitoneal injection of TCS-OX2-29 (orexin type-2 receptor antagonist). Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is
Gruen, M E; Dorman, D C; Lascelles, B D X
A literature review identified six placebo-controlled studies of analgesics in client-owned cats with degenerative joint disease-associated pain. Five studies with 96 cats had available data. Caregiver responses on a clinical metrology instrument, Client-Specific Outcome Measure (CSOM), were compared to measured activity. Cats were categorised as 'successes' or 'failures' based on change in CSOM score and activity counts from baseline. Effect sizes based on CSOM score were calculated; factors that were associated with success/failure were analysed using logistic regression. Effect sizes ranged from 0.97 to 1.93. The caregiver placebo effect was high, with 54-74 per cent of placebo-treated cats classified as CSOM successes compared with 10-63 per cent of cats classified as successes based on objectively measured activity. 36 per cent of CSOM successes were also activity successes, while 19 per cent of CSOM failures were activity successes. No significant effects of cat age, weight, baseline activity, radiographic score, orthopaedic pain score or study type on CSOM success in the placebo groups were found. The caregiver placebo effect across these clinical trials was remarkably high, making demonstration of efficacy for an analgesic above a placebo difficult. Further work is needed to determine whether a potential placebo-by-proxy effect could benefit cats in clinical settings. British Veterinary Association.
Tigerstedt, I; Leander, P; Tammisto, T
The efficacy of mild analgesics after 160 various superficial operations was studied by comparing intravenous lysine-acetylsalicylate (LAS) 1.8 g, Litalgin 4 ml (metamizole = dipyrone 2.0 g+ pitophenone 8.0 mg) or paracetamol 0.5 g to oxycodone 4 mg. At 15 min postdrug, oxycodone 4 mg had the best peak effect but this significant (P less than 0.05) difference to mild analgesics disappeared at 30 min, and thereafter all test analgesics showed an equally low effect. Two-thirds of the patients anaesthetized without peroperative analgesics needed pain relief when recovering from superficial surgery. The need for pain relief was lowest after varicose vein operations 40% of the patients as compared to about 70% after other types of superficial surgery. In 42% of the patients requiring pain relief, the test analgesics alone gave sufficient pain relief. The rest needed an additional 5 mg of oxycodone, on average, to be comfortable. The combined use of mild analgesics and oxycodone for adequate pain relief did not seem to reduce the postdrug sedation as compared to oxycodone alone. The results indicate that in traditional clinical dosages LAS, dipyrone or paracetamol can substitute about 5 mg oxycodone but offer sufficient analgesia only in about 40% of the patients recovering from superficial surgery.
Full Text Available Background : Intraoperative depth of anesthesia may affect postoperative pain relief. This prospective, randomized, and observer-blinded study assessed the effect of intraoperative depth of anesthesia on the postoperative pain and analgesic requirements in patients undergoing laparoscopic cholecystectomy. Materials and Methods : A total of 80 patients were randomly divided into two groups of 40 each. A standard technique for anesthesia was followed in all patients. Depth of anesthesia was monitored by bispectral index (BIS and adjusted with 0.5 to 1.5% isoflurane in group S by addition of propofol in group B, if required, to maintain a BIS value of 45 to 40. Postoperative analgesia was provided by tramadol 1 mg/kg every 6 hours and rescue analgesia by morphine boluses. Postoperative pain was assessed by Visual analogue scale score at 0, 8, 16, and 24 hours. Results : The demographic characteristics were comparable in both groups. The mean BIS value in Group S was 63.32 ± 11.43 and 45.06 ± 15.31 in Group B, well in the range of 40 to 60, reflecting adequate hypnotic effect for general anesthesia. The mean arterial pressure was low in group B throughout the surgery (P<0.05-0.001. The pain score were lower in group B at 0 and 8 hours postoperatively when compared with group S (P<0.05. The rescue analgesic requirement was less in group B, compared with group S (P<0.05. Conclusion : Maintaining BIS to a value of 45 to 40 throughout the surgery results in better postoperative pain relief and decreased requirement of rescue analgesic without any untoward effect.
Pleticha, Josef; Heilmann, Lukas F; Evans, Christopher H; Asokan, Aravind; Samulski, Richard Jude; Beutler, Andreas S
Gene therapy with adeno-associated virus (AAV) has advanced in the last few years from promising results in animal models to >100 clinical trials (reported or under way). While vector availability was a substantial hurdle a decade ago, innovative new production methods now routinely match the scale of AAV doses required for clinical testing. These advances may become relevant to translational research in the chronic pain field. AAV for pain targeting the peripheral nervous system was proven to be efficacious in rodent models several years ago, but has not yet been tested in humans. The present review addresses the steps needed for translation of AAV for pain from the bench to the bedside focusing on pre-clinical toxicology. We break the potential toxicities into three conceptual categories of risk: First, risks related to the delivery procedure used to administer the vector. Second, risks related to AAV biology, i.e., effects of the vector itself that may occur independently of the transgene. Third, risks related to the effects of the therapeutic transgene. To identify potential toxicities, we consulted the existing evidence from AAV gene therapy for other nervous system disorders (animal toxicology and human studies) and from the clinical pharmacology of conventional analgesic drugs. Thereby, we identified required preclinical studies and charted a hypothetical path towards a future phase I/II clinical trial in the oncology-palliative care setting.
Shah, Madeha; Parveen, Zahida; Khan, Muhammad Rashid
Saponins are the main constituents of genus Sapindus and have the therapeutic potential for inflammatory disorders. In this study the antioxidant, anti-inflammatory, analgesic and antipyretic potential of the stem bark of soap nut (Sapindus mukorossi) methanol extract and its derived fractions has been investigated. Powder of stem bark of the S. mukorossi was extracted with methanol (SMM) and fractionated in order of n-hexane (SMH), chloroform (SMC), ethyl acetate (SME), n-butanol (SMB) and the remaining as aqueous fraction (SMA). Quantitative estimation for the total phenolic and total flavonoid content was carried out in all the extract/fractions. Further, various in vitro antioxidant assays were also performed. Anti-inflammatory (Carrageenan induced paw edema), analgesic (hot plate latency test) and antipyretic (rectal temperature) were determined in Sprague-Dawley rat. Quantitative estimation of total phenolic contents in extract/fractions varied between 252.3 ± 2.41 mg of GAE/g - 594.16 ± 4.3 mg of GAE/g while the total flavonoids estimated were from 11.02 ± 1.3 mg of RUE/g to 96.9 ± 3.2 mg of RUE/g. Standard antioxidant assays such as scavenging of DPPH, hydroxyl radical, nitric oxide, phosphomolybdenum assay, reducing power, inhibition of β-carotene bleaching, iron chelation activity and inhibition of heat induced protein denaturation indicated the antioxidant potential of the extract/fractions. Carrageenan induced paw edema of rat was effectively inhibited by SMA at 300 mg/kg administration to rat (84.19 ± 1.48%) after 3 h and analgesia (latency time) in hot plate test (55.78 ± 1.22%) after 120 min. SMA at 300 mg/kg distinctly decreased the rectal temperature in brewer's yeast (Saccharomyces cerevisiae) induced pyrexia in rat. The resulted obtained in this study suggested the therapeutic importance of stem bark of S. mukorossi in inflammatory related disorders.
Zhao, Ya-Qun; Wang, Hai-Yan; Yin, Jun-Bin; Sun, Yan; Wang, Yong; Liang, Jin-Chuan; Guo, Xiao-Ju; Tang, Ke; Wang, Yu-Tong
The non-steroidal anti-inflammatory drug celecoxib has long been used for reducing pain, in spite of moderate gastrointestinal side effects. In previous studies, it has been shown that celecoxib can inhibit formalin-induced spontaneous pain and secondary hyperalgesia. Injecting formalin into a rodent's hind paw not only induces acute pain behaviors, but also produces long-lasting hyperalgesia. Whether celecoxib can also have long-lasting effects is still unknown. Our results show that pretreatment with an intraperitoneal injection of celecoxib at one hour before formalin injection induced inhibition on the spontaneous flinch and licking behaviors in the second phase but not the first phase. Meanwhile, FOS expressions were also reduced with celecoxib pretreatment. Consecutive administration of celecoxib also protects the hind paw from hypoalgesia and relieves formalin-induced, long-lasting hyperalgesia in the ipsilateral hind paw. These analgesic effects may be related to suppression of the activation of neurons and astrocytes indicated by FOS and GFAP expressions. Based on the above findings, celecoxib demonstrated analgesic effects not only on acute spontaneous pain behavior but also on long-lasting hyperalgesia induced by formalin injection. The inhibition of neurons and astrocytes by celecoxib may be possible reasons for its analgesia.
Mohammad Abdullah Al Masud
Full Text Available The present study was designed to evaluate the prescribing pattern of analgesics in post-operative patients in a surgical unit. Total number of 180 prescriptions containing analgesics was collected randomly. The only drug in the operation day that was used was pethidine (90.6%. Patients (9.4% did not receive any analgesics in the operation day. Associated analgesics in the operation day were either tramadol (42.2 % or ketorolac (54.4%. Only 3.3% did not receive any such drugs. In first post-operative day most of the patients received single drug tramadol (48.3%, ketorolac (38.9% and pethidine (0.6%. In second, third, forth and fifth post-operative day most patients received tramadol (47.8% (44.4%, (41.4% and (33.2% respectively. In sixth post-operative day most of the patients (81.1% did not receive any analgesics. In this study tramadol was found to be widely used post-operative analgesics with minimal side effects and better adherence to this drug by the patient.
Mohammad Abdullah Al Masud
Full Text Available The present study was designed to evaluate the prescribing pattern of analgesics in post-operative patients in a surgical unit. Total number of 180 prescriptions containing analgesics was collected randomly. The only drug in the operation day that was used was pethidine (90.6%. Patients (9.4% did not receive any analgesics in the operation day. Associated analgesics in the operation day were either tramadol (42.2 % or ketorolac (54.4%. Only 3.3% did not receive any such drugs. In first post-operative day most of the patients received single drug tramadol (48.3%, ketorolac (38.9% and pethidine (0.6%. In second, third, forth and fifth post-operative day most patients received tramadol (47.8% (44.4%, (41.4% and (33.2% respectively. In sixth post-operative day most of the patients (81.1% did not receive any analgesics. In this study tramadol was found to be widely used post-operative analgesics with minimal side effects and better adherence to this drug by the patient.
Oztekin, Deniz Seher; Oztekin, Ilhan; Issever, Halim; Göksel, Onur; Cinar, Bayer; Canik, Sevim
Critical care nurses and physicians are familiar with the principles of patient controlled analgesia and the opioid analgesics' regimens and observations necessary for pain control in the postoperative cardiac surgical patients. The objective of the study was to compare the effects of morphine, fentanyl, meperidine, remifentanil and tramadol which were administered by patient controlled analgesia and continuous intravenous infusion combination on the various parameters. This study was designed as prospective randomised trial. Fifty patients undergone open heart surgery with sternotomy were entered equally into five randomized groups. Visual analog scale was used by researcher nurse to assess the patient' pain status. Respiratory rate, heart rate and blood gases (pO2, pCO2, SaO2), radial arterial blood pressures were measured in the first 24 hrs postoperatively. Bolus requirements were determined by physicians and side effects of the analgesics were documented. Fentanyl group showed statistically higher levels of mean pO2 (p=0.002). Meperidine had the lowest number of bolus doses (p=0.001). There were no significant differences between the groups for pain management except higher visual analog scales on tramadol. Headache, stomach-ache and, palpitations were observed in our patients. Remifentanil, meperidine, fentanyl and morphine showed similar effect with each other for pain relief except tramadol.
M. A. Cimmino; P. Trezzi; Maio, T
Objective: Pure analgesics are only rarely used by Italian clinicians and this holds true also for rheumatologists. This work is concerned with an evaluation of the use of analgesics in a rheumatological outpatient clinic during the period 1989-1999. Methods: The records of 1705 patients consecutively seen at the clinic were downloaded on a specifically built website. Results: 4469 visits were considered. In 260 of them (5.8%), analgesics were prescribed to 234 (13.7%) patients. The number of...
Erkert, Ronald S; MacAllister, Charles G; Payton, Mark E; Clarke, Cyril R
To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered i.v. at typical clinical doses in horses with navicular syndrome. 12 horses with navicular syndrome that were otherwise clinically normal. Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCI; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome.
Navvabi Rigi Shahindokht
Full Text Available Abstract Background Primary dysmenorrhea is a common and sometimes disabling condition. In recent years, some studies aimed to improve the treatment of dysmenorrhea, and therefore, introduced several therapeutic measures. This study was designed to compare the analgesic effect of iron chip containing heat wrap with ibuprofen for the treatment of primary dysmenorrhea. Methods In this randomized (IRCT201107187038N2 controlled trial, 147 students (18–30 years old with the diagnosis of primary dysmenorrhea were enrolled considering the CONSORT guideline. Screening for primary dysmenorrhea was done by a two-question screening tool. The participants were randomly assigned into one of the intervention groups (heat Patch and ibuprofen. Data regarding the severity and emotional impact of the pain were recorded by a shortened version of McGill Pain Questionnaire (SF-MPQ. Student's t test was used for statistical analysis. Results The maximum and minimum pain severities were observed at 2 and 24 hours in both groups. The severity of sensual pain at 8, 12, and 24 hours was non-significantly less in the heat Patch group. There was also no significant difference between the groups regarding the emotional impact of pain at the first 2, 4, 8, 12 and 12 hours of menstruation. Conclusions Heat patch containing Iron chip has comparable analgesic effects to ibuprofen and can possibly be used for primary dysmenorrhea. Trial registration IRCT201107187038N2
Willy, Mary E; Graham, David J; Racoosin, Judith A; Gill, Rajdeep; Kropp, Garner F; Young, Jessica; Yang, Jeff; Choi, Joyce; MaCurdy, Thomas E; Worrall, Chris; Kelman, Jeffrey A
The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO. Wiley Periodicals, Inc.
Liu, He; Zhang, Hong-Xing; Hou, Hui-Yan; Lu, Xian-Fu; Wei, Jing-Qiu; Wang, Chun-Guang; Zhang, Li-Cai; Zeng, Yin-Ming; Wu, Yong-Ping; Cao, Jun-Li
Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the sciatic nerve selectively blocked the sensory but not the motor
further various other modalities of analgesia. Spinal morphine. Effectiveness. There is no doubt that morphine provides 12-24 hours of effective postoperative analgesia.1. Adverse effects. Adverse effects include pruritus, nausea and vomiting and respiratory depression.1 Of these, respiratory depression is the most feared.
ElMouedden, M.; Meert, T.F.
The intramedulary injection of osteosarcoma cells in the mouse femur has served as a laboratory model to study bone cancer pain. However, the efficacy of different classes of analgesics has not fully been analyzed in this model. Therefore, the acute antinociceptive properties of different classes of
Wang, Pei; Zhang, Peng; Wu, Gui-Wen; Hu, Shang-Qing; Li, Jing; Sun, Jun-Jun; Wang, Ya-Feng; Zhao, Min-Yi; Hu, Ni-Juan; Zhu, Jiang
To observe the analgesic effect of deqi induced by needling at Sanyinjiao (SP 6) on primary dysmenorrheal (PD) patients with cold damp stagnation syndrome (CDSS). A total of 64 PD patients with CDSS experiencing abdominal pain (≥40 mm in visual analogue scale ，VAS) were randomly assigned into deqi -expectation(DE) group( n ＝15) and no- deqi -expectation(NDE) group( n ＝49). On the first day of abdominal pain attack, bilateral SP 6 were punctured respectively with thicker needles with deeper insertion for deqi -expectation patients and thin filiform needles with shallow insertion for no- deqi -expectation patients. The needles were removed after 30 minutes, a deqi scale was used to evaluate the deqi condition. According to the results, patients in the DE group were further divided into deqi DE group and no- deqi DE group, patients in the NDE group were also divided into deqi NDE group and no- deqi NDE group. The VAS was used to evaluate the patients' abdominal pain severity before treatment and 0, 10, 20, 30 min after acupuncture needle withdrawal. The rate of deqi in the DE group was higher than that in the NDE group( P <0.05). The VAS scores of abdominal pain in the four groups were decreased at all time-points after needle withdrawal compared with those before treatment ( P <0.01), while the VAS score in the deqi DE group were lower than in the no- deqi NDE group 30 min after needle withdrawal ( P <0.05). The intervention method of thick needle, deep insertion and some manipulation is easier in inducing deqi than that of thin needle, shallow insertion and no manipulation. The analgesic effect of deqi is better than that of no- deqi for PD patients with CDSS.
Full Text Available A series of schiff base derivatives of 4-aminophenazone (4APZ-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one with different aldehydes were synthesized. The synthetic compounds were screened for their anti-inflammatory, analgesic and antipyretic activities. The characterization of synthesized compounds was carried out by 1H NMR, 13C NMR and MS. Carrageenan-induced paw oedema (CIPO and histamine induced paw oedema (HIPO methods were used to determine the anti-inflammatory activity of commercial sample of 4APZ and its synthesized schiff bases in mice. The anti-inflammatory activity was in the order of 4APZAB > 4APZBB > 4APZCB > 4APZVn and all the test compounds exhibited considerable dose dependent inhibition of the paw oedema. The effect of the compounds on membrane stabilization was also determined which showed that compounds 4APZ (120 and 240 mg/kg doses, 4APZAB (160 mg/kg and 4APZVn (600 mg/kg produced highly significant inhibition (P 4APZBB > 4APZVn > 4APZCB. Moreover, phenobarbitone-induced sleeping time (PIST in mice was also studied but only 600 mg/kg of 4APZVn significantly increased the duration of induced sleep which also suggested its sedative property. Brewer’s yeast was used to induce fever in rabbits and analysed the compounds for their antipyretic activity. Different doses of 4APZ for different time durations (240 mg/kg-after 1 h, 120 and 240 mg/kg doses-after 2 h produced highly significant (P < 0.001 inhibition of hyperpyrexia. Other compounds showed good antipyretic activity after 2, 3 and 4 h.
Andersen, L Ø; Husted, H; Kristensen, B B
High-volume wound local infiltration analgesia is effective in knee arthroplasty, but the analgesic efficacy of subcutaneous wound infiltration has not been evaluated.......High-volume wound local infiltration analgesia is effective in knee arthroplasty, but the analgesic efficacy of subcutaneous wound infiltration has not been evaluated....
used.5 The optimal dose (balancing effective analgesia and a low incidence of adverse effects) most probably .... In open and laparoscopic abdominal surgery, as well as in ambulatory surgery, intravenous perioperative ... impact on postoperative analgesia in patients undergoing tonsillectomy, hip arthroplasty and coronary ...
Full Text Available Barth L Wilsey,1,2 Reena Deutsch,3 Emil Samara,4 Thomas D Marcotte,3 Allan J Barnes,5 Marilyn A Huestis,5,6 Danny Le1,2 1VA Northern California Health Care System, Mather, CA, 2Department of Physical Medicine and Rehabilitation, University of California, Sacramento, CA, 3Department of Psychiatry, University of California, San Diego, La Jolla, CA, 4PharmaPolaris International, Davis, CA, 5Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, Baltimore, MD, 6University of Maryland School of Medicine, Baltimore, MD, USA Abstract: A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its nonpsychotropic metabolite, 11-nor-9-carboxy-THC, were related to percent change from baseline of several descriptors (eg, itching, burning, and deep pain. However, given the large number of multiple comparisons, false-discovery-rate-adjusted P-values were not significant. Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids. Such an
Osman, Walla'a A; Labib, Dina A; Abdelhalim, Mona O; Elrokh, Elsayed M
Olive oil was used in the past as a remedy for many diseases due to its unlimited benefits in health. This study was carried out to assess the analgesic, anti-pyretic and anti-inflammatory activities of extra virgin olive oil (EVOO) at a dose of 8 mL/kg body weight and to compare it with ibuprofen (IBU) as an individual drug therapy and in combination with two different doses of IBU (therapeutic dose 100 mg/kg and low dose 40 mg/kg), on different animal models in albino mice. A total of 132 adult healthy male Swiss albino mice were used in this study. The analgesic effect was assessed using acetic acid-induced writhing test. The antipyretic effect was evaluated by brewer's yeast-induced pyrexia, while the anti-inflammatory activity was assessed by two different models; the carrageenan-induced paw edema and the carrageenan-induced peritonitis in which the levels of total leukocyte count (TLC), neutrophil count, prostaglandin E2 (PGE2) and interferon gamma (INF-γ) were measured in the peritoneal exudates. The results revealed significant protection in all the treated groups; however, the combination of EVOO with IBU at its therapeutic dose showed superiority over the two compounds when used separately. Using EVOO with the therapeutic dose of IBU showed synergistic effect in controlling the cardinal signs of acute inflammation rather than using non-steroidal anti-inflammatory drugs alone. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
Okokon, Jude E; Udoh, Anwanga E; Frank, Samuel G; Amazu, Louis U
Objective To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods The crude leaf extract (39–111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results The extract caused a significant (P<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant. PMID:23569885
Full Text Available Abstract Background Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. Methods The chronic constrictive injury (CCI model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC group, CCI group, and CCI with electroacupuncture (EA stimulation group. EA was applied to bilateral Zusanli (ST36 and Yanglingquan (GB34 in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. Results After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold, which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK signaling”. Conclusions These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.
Gao, Hua-Li; Xiao, Lian-Bo; Zhai, Wei-Tao; He, Yong; Zhu, Fei; Zheng, Lin; Han, Xiu-Wei
To compare the analgesic effect between multimodal and patient-controlled intravenous analgesia(PCIA) in patients with rheumatoid arthritis(RA) in the perioperative period of knee joint replacement. From June 2015 to June 2016, 40 RA patients undergoing total knee arthroplasty were randomly divided into two groups. There were 20 patients in PCIA group, including 3 males and 17 females, with an average age of(59.6±2.3) years old, who received controlled instillation of sufentanil analgesia controlled by an intravenous analgesia pump. There were 20 patients in multiple model analgesia group, including 2 males and 18 females, with an average age of(56.3±1.3) years old, who were treated with continuous femoral nerve block, local injection of knee joint and combined buprenorphine patches. The VAS score and the incidence of adverse reactions and HSS score were compared between the two groups after operation. The advantages and disadvantages of the two modes of analgesia were evaluated. On the 6 th and 24 th hours after surgery, the VAS scores of the multimodal analgesia group were significantly lower than those of the PCIA group( P multimodal analgesia group than those in PCIA group( P multimodal analgesia group was significantly higher than that in the PCIA group( P multimodal analgesia group were better than those in PCIA group ( P multimodal analgesia group was significantly better than that of PCIA group( P Multimodal analgesia is an ideal analgesic plan for total knee arthroplasty TKA patients with RA in perioperative period, which has good effects and little adverse reaction.
Zhao, Min-Yi; Zhang, Peng; Li, Jing; Wang, Lin-Peng; Zhou, Wei; Wang, Yan-Xia; She, Yan-Fen; Ma, Liang-Xiao; Wang, Pei; Hu, Ni-Juan; Lin, Chi; Hu, Shang-Qin; Wu, Gui-Wen; Wang, Ya-Feng; Sun, Jun-Jun; Jiang, Si-Zhu; Zhu, Jiang
The aim of this multicentre randomised controlled trial was to investigate the contribution of de qi to the immediate analgesic effect of acupuncture in patients with primary dysmenorrhoea and the specific traditional Chinese medicine diagnosis cold and dampness stagnation . Eighty-eight patients with primary dysmenorrhoea and cold and dampness stagnation were randomly assigned to de qi (n=43) or no de qi (n=45) groups and underwent 30 min of SP6 acupuncture. The de qi group received deep needling at SP6 with manipulation using thick needles; the no de qi group received shallow needling with no manipulation using thin needles. In both groups the pain scores and actual de qi sensation were evaluated using a visual analogue scale for pain (VAS-P) and the acupuncture de qi clinical assessment scale (ADCAS), respectively. Both groups showed reductions in VAS-P, with no signficant differences between groups. ADCAS scores showed 43/43 and 25/45 patients in de qi and no de qi groups, respectively, actually experienced de qi sensation. Independent of original group allocation, VAS-P reductions associated with actual de qi (n=68) were greater than those without (28.4±18.19 mm vs 14.6±12.28 mm, p=0.008). This study showed no significant difference in VAS-P scores in patients with primary dysmenorrhoea and cold and dampness stagnation immediately after SP6 acupuncture designed to induce or avoid de qi sensation. Both treatments significantly reduced VAS-P relative to baseline. Irrespective of group allocation, patients experiencing actual de qi sensation demonstrated larger reductions in pain score relative to those without, suggesting greater analgesic effects. Chinese Clinical Trial Registry (ChiCTR-TRC-13003086); Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Purpose: To evaluate synergy in the analgesic effects of a combination therapy of carbamazepine (CBZ) and gabapentin (GBP) in diabetic neuropathic pain. Methods: Neuropathic pain was produced in rats by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. CBZ, GBP, and their combination were orally ...
Maihöfner, Christian; Ringler, Ralf; Herrndobler, Franz; Koppert, Wolfgang
One of the most distressing symptoms of many neuropathic pain syndromes is the enhanced pain sensation to tactile or thermal stimulation (hyperalgesia). In the present study we used functional magnetic resonance imaging (fMRI) and explored brain activation patterns during acute impact pain and mechanical hyperalgesia in the human ultraviolet (UV)-B model. To investigate pharmacological modulation, we examined potential differential fMRI correlates of analgesic and antihyperalgesic effects of two intravenous cyclooxygenase inhibitors, i.e. parecoxib and acetylsalicylic acid (ASA). Fourteen healthy volunteers participated in this double-blinded, randomized and placebo-controlled crossover study. Tactile stimuli and mechanical impact hyperalgesia were tested at the site of a UV-B irradiation and acute mechanical pain was tested at a site distant from the irradiated skin. These measurements were conducted before and 30 min after a 5-min intravenous infusion of either saline (placebo), parecoxib 40 mg or ASA 1000 mg. Acute mechanical pain and mechanical hyperalgesia led to widespread activations of brain areas known to comprise the human pain matrix. Analgesic effects were found in primary (S1) and secondary (S2) somatosensory cortices, parietal association cortex (PA), insula, anterior parts of the cingulate cortex and prefrontal cortices. These brain areas were also modulated under antihyperalgesic conditions. However, we observed a greater drug-induced modulation of mainly PA and inferior frontal cortex during mechanical hyperalgesia; during acute mechanical pain there was a greater modulation of mainly bilateral S2. Therefore, the results of the present study suggest that there is a difference in the brain areas modulated by analgesia and antihyperalgesia.
Graversen, Carina; Olesen, Søren S; Olesen, Anne E; Steimle, Kristoffer; Farina, Dario; Wilder-Smith, Oliver H G; Bouwense, Stefan A W; van Goor, Harry; Drewes, Asbjørn M
AIM To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain. METHODS This was a double-blind, placebo-controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75 mg–300 mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on a visual analogue scale. In addition, brief pain inventory-short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi-channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated. RESULTS Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5–7.5 Hz), difference of −3.18, 95% CI −3.57, −2.80; P = 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients was seen in the parietal region, with a classification accuracy of 85.7% (P = 0.009). Individual changes in EEG indices were correlated with changes in pain diary (P = 0.04) and BPI pain composite scores (P = 0.02). CONCLUSIONS Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine. PMID:21950372
Jamison, Robert N; Mao, Jianren
Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Henriksen, Marius; Hansen, Julie B; Klokker, Louise; Bliddal, Henning; Christensen, Robin
Evidence of comparative effectiveness of different treatment approaches is important for clinical decision-making, yet absent for most recommended treatments of knee osteoarthritis pain. The objective of this study was to estimate the comparative effectiveness of exercise versus orally administered analgesics for pain in patients with knee osteoarthritis. The Cochrane Database of systematic reviews was searched for meta-analyses of randomized controlled studies comparing exercise or analgesics with a control group (placebo or usual care) and with pain as an outcome. Individual study estimates were identified and effect sizes were calculated from group differences. We combined study-level effects on pain with a random effects meta-analysis and compared effect sizes between exercise trials and trials with analgesic interventions. We included six Cochrane reviews (four pharmacology, two exercise). From these, 54 trials were eligible (20 pharmacology, 34 exercise), with 9806 participants (5627 pharmacology, 4179 exercise). The pooled effect size of pharmacological pain interventions was 0.41 (95% CI: 0.23-0.59) and for exercise 0.46 standardized mean difference (95% CI: 0.34-0.59). There was no statistically significant difference between the two types of intervention (difference: 0.06 standardized mean difference [95% CI: -0.28-0.16; p = 0.61]). This meta-epidemiological study provides indirect evidence that for knee osteoarthritis pain, the effects from exercise and from oral analgesics are comparable. These results may support shared decision-making where a patient for some reason is unable to exercise or who consider exercise as unviable and analgesics as a more feasible choice. PROSPERO registration: CRD42013006924.
Holsgaard-Larsen, A; Clausen, B; Søndergaard, J; Christensen, R; Andriacchi, T P; Roos, E M
To investigate the effect of a neuro-muscular exercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis (OA). We hypothesized that knee joint loading during walking would be reduced by NEMEX and potentially increased by PHARMA. Single-blind, randomized controlled trial (RCT) comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee OA were randomly allocated (1:1) to one of two 8-week treatments. Primary outcome was change in knee load during walking (Knee Index, a composite score from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes were frontal plane peak knee adduction moment (KAM), Knee Injury and Osteoarthritis Outcome Scores (KOOS) and functional performance tests. Ninety three participants (57% women, 58 ± 8 years with a body mass index [BMI] of 27 ± 4 kg/m2 (mean ± standard deviation [SD])) were randomized to NEMEX group (n = 47) or PHARMA (n = 46); data from 44 (94%) and 41 (89%) participants respectively, were available at follow-up. 49% of the participants in NEMEX and only 7% in PHARMA demonstrated good compliance. We found no difference in the primary outcome as evaluated by the Knee Index -0.07 [-0.17; 0.04] Nm/%BW HT. Secondary outcomes largely supported this finding. We found no difference in the primary outcome; knee joint load change during walking from a NEMEX program vs information on the recommended use of analgesics and anti-inflammatory drugs. ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012). Ethical Committee: S-20110153. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Shemesh, Maoz; Zilberman, Meital
Over the last decades, wound dressings have developed from the traditional gauze dressing to tissue-engineered scaffolds. A wound dressing should ideally maintain a moist environment at the wound surface, allow gas exchange, act as a barrier to micro-organisms and remove excess exudates. In order to provide these characteristics, we developed and studied bioresorbable hybrid structures which combine a synthetic porous drug-loaded top layer with a spongy collagen sublayer. The top layer, prepared using the freeze-drying of inverted emulsions technique, was loaded with the analgesic drugs ibuprofen or bupivacaine, for controlled release to the wound site. Our investigation focused on the effects of the emulsion's parameters on the microstructure and on the resulting drug-release profile, as well as on the physical and mechanical properties. The structure of the semi-occlusive top layer enables control over vapor transmission, in addition to strongly affecting the drug release profile. Release of the analgesic drugs lasted from several days to more than 100 days. Higher organic:aqueous phase ratios and polymer contents reduced the burst release of both drugs and prolonged their release due to a lower porosity. The addition of reinforcing fibers to this layer improved the mechanical properties. Good binding of the two components, PDLGA and collagen, was achieved due to our special method of preparation, which enables a third interfacial layer in which both materials are mixed to create an "interphase". These new PDLGA/collagen structures demonstrated a promising potential for use in various wound healing applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Sanz, Macarena G; Sellon, Debra C; Cary, Julie A; Hines, Melissa T; Farnsworth, Kelly D
To compare the analgesic efficacy of administration of butorphanol tartrate, phenylbutazone, or both drugs in combination in colts undergoing routine castration. Randomized controlled clinical trial. 36 client-owned colts. Horses received treatment with butorphanol alone (0.05 mg/kg [0.023 mg/lb], IM, prior to surgery and then q 4 h for 24 hours), phenylbutazone alone (4.4 mg/kg [2.0 mg/lb], IV, prior to surgery and then 2.2 mg/kg [1.0 mg/lb], PO, q 12 h for 3 days), or butorphanol and phenylbutazone at the aforementioned dosages (12 horses/group). For single-drug-treated horses, appropriate placebos were administered to balance treatment protocols among groups. All horses were anesthetized, and lidocaine hydrochloride was injected into each testis. Physical and physiological variables, plasma cortisol concentration, body weight, and water consumption were assessed before and at intervals after surgery, and induction of and recovery from anesthesia were subjectively characterized. Observers assessed signs of pain by use of a visual analogue scale and a numerical rating scale. Significant changes in gastrointestinal sounds, fecal output, and plasma cortisol concentrations were evident in each treatment group over time, compared with preoperative values. At any time point, assessed variables and signs of pain did not differ significantly among groups, although the duration of recumbency after surgery was longest for the butorphanol-phenylbutazone-treated horses. With intratesticular injections of lidocaine, administration of butorphanol to anesthetized young horses undergoing routine castration had the same apparent analgesic effect as phenylbutazone treatment. Combined butorphanolphenylbutazone treatment was not apparently superior to either drug used alone.
Hansen, Tine Maria; Olesen, Anne Estrup; Simonsen, Carsten Wiberg
BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective...
Quantification of polyphenols and evaluation of antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava.
de Araújo, Aurigena Antunes; Soares, Luiz Alberto Lira; Assunção Ferreira, Magda Rhayanny; de Souza Neto, Manoel André; da Silva, Giselle Ribeiro; de Araújo, Raimundo Fernandes; Guerra, Gerlane Coelho Bernardo; de Melo, Maria Celeste Nunes
Vast numbers of plant species from northeastern Brazil have not yet been phytochemically or biologically evaluated. The goal of this work was to obtain, characterize and show the antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava. The plant material (100g) was dried, and the crude extracts were obtained by using turbo-extraction (10%; w/v) with water or acetone:water (7:3, v/v) as the extraction solvent. High-performance liquid chromatography (HPLC) methods were used to screen the crude extracts for hydrolysable tannins (gallic acid) and condensed tannins (catechins). The antibacterial activity was evaluated by agar-diffusion and microdilution methods against Gram-positive strains (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis INCQS 00016, Enterococcus faecalis ATCC 29212 and a clinical isolate of methicillin-resistant Staphylococcus aureus) as well as Gram-negative strains (Escherichia coli ATCC 25922, Salmonella enteritidis INCQS 00258, Shigella flexneri and Klebsiella pneumoniae). To evaluate the anti-inflammatory activity, a leukocyte migration model was used. Analgesic activity was determined by the hot plate test and the acetic acid-induced abdominal writhing test. Data were analyzed by analysis of variance (ANOVA) at a significance level of 5%. Parapiptadenia rigida presented the highest amount of total polyphenols (35.82 ± 0.20%), while the greatest catechin content was found in the acetone-water extract of Psidium guajava (EAWPg; 1.04 μg/g). The largest amounts of catechins were found in the aqueous extract of Libidibia ferrea (EALf; 1.07 μg/g) and the acetone-water extract of Parapiptadenia rigida (EAWPr; 1.0 μg/g). All extracts showed activity against Gram-positive bacteria. The aqueous and acetone-water extracts of Psidium guajava showed the greatest inhibition zones in the agar diffusion tests. In the evaluation of the minimum
Conclusion: Combining paracetamol with ibuprofen enhances analgesic/anti-inflammatory activity over their individual component but potentiation of analgesic activity of diclofenac was not seen when paracetamol was added to it.
Full Text Available Paracetamol also known as acetaminophen, is a widely used analgesic and antipyretic agent. We report the synthesis and biological evaluation of adamantyl analogues of paracetamol with important analgesic properties. The mechanism of nociception of compound 6a/b, an analog of paracetamol, is not exerted through direct interaction with cannabinoid receptors, nor by inhibiting COX. It behaves as an interesting selective TRPA1 channel antagonist, which may be responsible for its analgesic properties, whereas it has no effect on the TRPM8 nor TRPV1 channels. The possibility of replacing a phenyl ring by an adamantyl ring opens new avenues in other fields of medicinal chemistry.
Full Text Available Abstract Background Electrical acupuncture (EA has been utilized in acute pain management. However, the neuronal mechanisms that lead to the analgesic effect are still not well defined. The current study assessed the intensity [optimal EA (OI-EA vs. minimal EA (MI-EA] effect of non-noxious EA on supraspinal regions related to noxious heat pain (HP stimulation utilizing an EA treatment protocol for acute pain and functional magnetic resonance imaging (fMRI with correlation in behavioral changes. Subjects underwent five fMRI scanning paradigms: one with heat pain (HP, two with OI-EA and MI-EA, and two with OI-EA and HP, and MI-EA and HP. Results While HP resulted in activations (excitatory effect in supraspinal areas known for pain processing and perception, EA paradigms primarily resulted in deactivations (suppressive effect in most of these corresponding areas. In addition, OI-EA resulted in a more robust supraspinal sedative effect in comparison to MI-EA. As a result, OI-EA is more effective than MI-EA in suppressing the excitatory effect of HP in supraspinal areas related to both pain processing and perception. Conclusion Intensities of EA plays an important role in modulating central pain perception.
Huang, Shi-Rong; Shi, Yin-Yu; Zhan, Hong-sheng
To explore an effective method for electroacupuncture treatment of pain in waist and lower extremities due to prolapse of lumbar intervertebral disc. All 98 cases of such disease were randomly divided into a treatment group (n = 53) and a control group (n = 45). The treatment group were treated with local single-point electroacupuncture stimulation, and the control group with routine electroacupuncture stimulation for 8 sessions. The pain in waist and lower extremities in the two groups were continuously evaluated with short-form of McGill pain questionnaire (SF-MPQ). After first treatment, SF-MPQ scores in the two groups were significantly different from those before treatment (P prolapse of lumbar intervertebral disc.
Srebro, Dragana; Vučković, Sonja; Prostran, Milica
Previously we described the antinociceptive effect of magnesium sulfate and dizocilpine (MK-801) in the visceral and somatic rat models of pain. In the somatic model of pain, we established the influence of selective inhibitors of neuronal and inducible nitric oxide synthase on the antihyperalgesic effects of magnesium sulfate and dizocilpine. Therefore, the objective of the present study was to determine in the rat model of visceral pain whether same mechanisms are involved in the antinociceptive action of magnesium sulfate and dizocilpine. Analgesic activity was assessed using the acetic acid-induced writhing test in rats. Subcutaneous injection of either magnesium sulfate (15 mg/kg) or dizocilpine (0.01 mg/kg) decreased the number of writhes by about 60 and 70%, respectively. The role of nitric oxide on the effects of magnesium sulfate and dizocilpine was evaluated using selective inhibitor of neuronal (N-ω-Propyl-L-arginine hydrochloride (L-NPA)) and inducible (S-methylisothiourea (SMT)) nitric oxide synthase, which per se did not affect the number of writhes. We observed that the antinociceptive effect of magnesium sulfate or dizocilpine did not change in the presence of L-NPA (2 and 10 mg/kg, i.p.) and SMT (0.015 and 10 mg/kg, i.p.). We conclude that, nitric oxide produced by neuronal and inducible nitric oxide synthase does not modulate the effects of magnesium sulfate and dizocilpine in the visceral inflammatory model of pain in the rat.
Ismail, Hammad; Mirza, Bushra
Lactuca sativa (lettuce) has been traditionally used for relieving pain, inflammation, stomach problems including indigestion and lack of appetite. Moreover, the therapeutic significance of L. sativa includes its anticonvulsant, sedative-hypnotic and antioxidant properties. In the present study, the MC (methanol and chloroform; 1:1) and aqueous extracts of seed and leaf along with cell suspension exudate were prepared. These extracts were explored for their analgesic, anti-inflammatory, antidepressant and anticoagulant effects by hot plate analgesic assay; carrageenan induced hind paw edema test, forced swimming test and capillary method for blood clotting respectively in a rat model. The results were analyzed using one-way Analysis of Variance (ANOVA) followed by Turkey multiple comparison test. Interestingly, the extracts and the cell suspension exudate showed dual inhibition by reducing pain and inflammation. The results indicated that the aqueous extracts of leaf exhibited highest analgesic and anti-inflammatory activities followed by leaf MC, cell suspension exudate, seed aqueous and seed MC extracts. The current findings show that aqueous and MC extracts of seed have the least immobility time in the forced swimming test, which could act as an anti-depressant on the central nervous system. The leaf extracts and cell suspension exudate also expressed moderate anti-depressant activities. In anticoagulant assay, the coagulation time of aspirin (positive control) and MC extract of leaf was comparable, suggesting strong anti-coagulant effect. Additionally, no abnormal behavior or lethality was observed in any animal tested. Taken together, L. sativa can potentially act as a strong herbal drug due to its multiple pharmaceutical effects and is therefore of interest in drug discovery and development of formulations.
Barbosa, Joana; Faria, Juliana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused
Moyano, Jairo; García, Maria; Caicedo, Maria
Background. Dexamethasone is sometimes used as a coanalgesic because of its anti-inflammatory properties. Objective. To evaluate opioid use, postoperative pain intensity, and side effects after a single dose of dexamethasone in patients undergoing arthroscopic knee surgery. Methods. In this randomized controlled study patients were randomized to receive either 10 mg of intravenous dexamethasone (DM group) or 0.9% normal saline (NS group) during the intraoperative period. Primary outcomes were pain intensity and total morphine and codeine use after surgery. Results. Seventy-eight patients were included in the study. The DM group showed statistically significant higher pain intensity at the fourth postoperative hour (DM: 3.96/10, standard deviation [SD] 0.54; NS: 2.46/10, SD 0.45; p = 0.036). No statistically significant difference in total opioid use (morphine plus codeine) was identified with 15.9 (SD 1.97) codeine tablets used in DM group and 20 (SD 2.14) in NS group (p = 0.25). Discussion. Pain intensity tended to decrease in both groups suggesting morphine as the main source of analgesia. Conclusions. Intravenous dexamethasone during the intraoperative period has no clinical impact on postoperative pain intensity during the first 48 h after arthroscopic knee surgery. This trial is registered with R000020892.
Full Text Available Background. Dexamethasone is sometimes used as a coanalgesic because of its anti-inflammatory properties. Objective. To evaluate opioid use, postoperative pain intensity, and side effects after a single dose of dexamethasone in patients undergoing arthroscopic knee surgery. Methods. In this randomized controlled study patients were randomized to receive either 10 mg of intravenous dexamethasone (DM group or 0.9% normal saline (NS group during the intraoperative period. Primary outcomes were pain intensity and total morphine and codeine use after surgery. Results. Seventy-eight patients were included in the study. The DM group showed statistically significant higher pain intensity at the fourth postoperative hour (DM: 3.96/10, standard deviation [SD] 0.54; NS: 2.46/10, SD 0.45; p=0.036. No statistically significant difference in total opioid use (morphine plus codeine was identified with 15.9 (SD 1.97 codeine tablets used in DM group and 20 (SD 2.14 in NS group (p=0.25. Discussion. Pain intensity tended to decrease in both groups suggesting morphine as the main source of analgesia. Conclusions. Intravenous dexamethasone during the intraoperative period has no clinical impact on postoperative pain intensity during the first 48 h after arthroscopic knee surgery. This trial is registered with R000020892.
Elzaki, Wail M; Ziada, Hassan M; Abubakr, Neamat H; Ibrahim, Yahia E
This study aimed to evaluate the secondary outcomes of gender and arch and their impact on pain reduction following initial endodontic therapy. 185 medications, including placebo were prepared, and 170 participants completed the trial. Group 1, received a single dose of Paracetamol alone (G-1), Group 2 received combined Ibuprofen/Paracetamol (G-2). Group 3 received combined Mefenamic acid/Paracetamol (G-3), group 4 received combined Diclofenac K/Paracetamol (G-4) and Group 5 received a placebo (G-5). There were no statistically significant differences in pain reduction between males and females whilst there were statistically significant differences between them and the placebo group. All combinations of Paracetamol performed better in pain reduction than the placebo among females, while there were no statistically significant differences among males. In conclusion, there were no differences in pain reduction between males and females, and arch for the tested analgesics taken immediately following initial endodontic therapy in teeth with irreversible pulpitis. © 2017 Australian Society of Endodontology Inc.
Villarreal, Eduardo A Garza; Brattico, Elvira; Vase, Lene; Østergaard, Leif; Vuust, Peter
Listening to music has been found to reduce acute and chronic pain. The underlying mechanisms are poorly understood; however, emotion and cognitive mechanisms have been suggested to influence the analgesic effect of music. In this study we investigated the influence of familiarity, emotional and cognitive features, and cognitive style on music-induced analgesia. Forty-eight healthy participants were divided into three groups (empathizers, systemizers and balanced) and received acute pain induced by heat while listening to different sounds. Participants listened to unfamiliar Mozart music rated with high valence and low arousal, unfamiliar environmental sounds with similar valence and arousal as the music, an active distraction task (mental arithmetic) and a control, and rated the pain. Data showed that the active distraction led to significantly less pain than did the music or sounds. Both unfamiliar music and sounds reduced pain significantly when compared to the control condition; however, music was no more effective than sound to reduce pain. Furthermore, we found correlations between pain and emotion ratings. Finally, systemizers reported less pain during the mental arithmetic compared with the other two groups. These findings suggest that familiarity may be key in the influence of the cognitive and emotional mechanisms of music-induced analgesia, and that cognitive styles may influence pain perception.
Eduardo A Garza Villarreal
Full Text Available Listening to music has been found to reduce acute and chronic pain. The underlying mechanisms are poorly understood; however, emotion and cognitive mechanisms have been suggested to influence the analgesic effect of music. In this study we investigated the influence of familiarity, emotional and cognitive features, and cognitive style on music-induced analgesia. Forty-eight healthy participants were divided into three groups (empathizers, systemizers and balanced and received acute pain induced by heat while listening to different sounds. Participants listened to unfamiliar Mozart music rated with high valence and low arousal, unfamiliar environmental sounds with similar valence and arousal as the music, an active distraction task (mental arithmetic and a control, and rated the pain. Data showed that the active distraction led to significantly less pain than did the music or sounds. Both unfamiliar music and sounds reduced pain significantly when compared to the control condition; however, music was no more effective than sound to reduce pain. Furthermore, we found correlations between pain and emotion ratings. Finally, systemizers reported less pain during the mental arithmetic compared with the other two groups. These findings suggest that familiarity may be key in the influence of the cognitive and emotional mechanisms of music-induced analgesia, and that cognitive styles may influence pain perception.
Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A
Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies
Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna
Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408
Tuk, Jacco G C; van Wijk, Arjen J; Mertens, Ine C; Keleş, Zühal; Lindeboom, Jérôme A H; Milstein, Dan M J
The aim of this study was to evaluate the analgesic effects of low-level laser therapy (LLLT) on preinjection sites in patients scheduled for third molar removal. This double-blind randomized controlled trial included 163 healthy patients undergoing third molar extractions. The study participants were randomly divided into an LLLT and a placebo group. Objective and subjective data sets were obtained from physiologic feedback (heart rate and sweat response) and a questionnaire, respectively. In the LLLT group, each targeted injection site was irradiated twice with 198 mW continuous wave for 30 seconds with a 0.088 cm(2) focal spot at an applied energy of 5.94 J and fluence of 67.50 J/cm(2). Measurements were recorded from 4 time-points during data acquisition. There was no significant difference between the LLLT and placebo groups in pain experience scores associated with the injected sites for maxillary or mandibular third molar extractions. Mean heart rates before and during injection were lower in the LLLT group than in the placebo group for both maxillary and mandibular regions. No statistically significant differences were observed for any remaining parameters. The present data indicated that preinjection LLLT did not effectively decrease the pain felt during local anesthetic injections before third molar surgery. Copyright © 2017 Elsevier Inc. All rights reserved.
de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel
Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals' nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3-L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals' nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression.
Full Text Available In Reply Dr. Ortiz and Dr. Romero-Quezada evaluated our study precisely and authors are grateful for their great survey on our article. There were some questions and concerns that we are going to answer. We wish it could help others to come up with better ideas and conclusions. 1. ACL tear may occur in two scenarios and we believe that there is not a third one: 1st- the ACL injury functionally disables the patient and becomes symptomatic; in this scenario the patient would suffer from giving way and the “Lachman test” is definitely positive (3+ or 4+ (1. Intra-operatively (post anesthesia “Pivot shift test” is almost positive in all cases. 2nd- ACL injury does not conflict with the patient’s routine and social activity and giving way are usually negative and Lachman test can be negative, 1+ and in the most severe condition 2+ positive. Partial ACL tear may be reported in MRI, however authors believe these cases do not benefit from a surgical intervention, and conservative treatment should be performed. 2. Although most of our patients were suffered from sports trauma, mechanisms of ACL tears were not the same in all patients. The duration between traumas to surgeries in all patients enrolled in this study were at least 6 weeks which were included the proceeding from acute trauma phase to performing physical therapy and accomplishing full range of motion pre-operatively. Since the present study was not about surgical technique and pre or post rehab protocols and programs, authors avoided such additional issues. 3. About Pethidine issue, this drug is the main protocol one in our hospital to provide analgesics for post-operative pain, so authors routinely decided to utilize the pethidine as analgesics such as recent relative article (2. We used the pethidine intravenously and by patient’s demand; if a patients requested for pain killers, we provided him/her with 0.5 mg-per-Kg pethidine which was injected intravenously. The time and
Full Text Available "nA multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and µ-opioid agonist tramadol, 100 mg (Group T and piroxicam 20 mg (Group P given IM alone- single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10, nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P>0.05. Pain intensity decreased markedly over time in both groups. Mean±SEM pain degrees were as follows: P=7.7±0.5, T=8.2±0.8 after 0 hours; P=5.4±0.6, T=6.1±0.5 after 6 hours; P=3.3±0.4, T=3.4±0.7 after 12 hours; P=1.1±0.4, T=1.3±0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.
Farshchi, Amir; Ghiasi, Golbarg
A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and mu-opioid agonist tramadol, 100 mg (Group T) and piroxicam 20 mg (Group P) given IM alone--single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10), nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P > 0.05). Pain intensity decreased markedly over time in both groups. Mean +/- SEM pain degrees were as follows: P = 7.7 +/- 0.5, T = 8.2 +/- 0.8 after 0 hours; P=5.4 +/- 0.6, T = 6.1 +/- 0.5 after 6 hours; P=3.3 +/- 0.4, T = 3.4 +/- 0.7 after 12 hours; P = 1.1 +/- 0.4, T = 1.3 +/- 0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy) could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.
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.
Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro
Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.
Majumdar, Susruta; Grinnell, Steven; Le Rouzic, Valerie; Burgman, Maxim; Polikar, Lisa; Ansonoff, Michael; Pintar, John; Pan, Ying-Xian; Pasternak, Gavril W
Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile.
Jørgensen, Mette Rose; Pedersen, Anne Marie Lynge
OBJECTIVE: To investigate the effectiveness of repeated topical application of oral capsaicin gel in two different concentrations for relief of burning/stinging sensations in patients with burning mouth syndrome (BMS). MATERIAL AND METHODS: This randomized double-blind cross-over study included 22...... female patients with BMS. The patients were randomized for topical application of either 0.01% or 0.025% oral capsaicin gel on the dorsal part of tongue three times daily for 14 days, followed by 14 days wash-out period, and finally treatment with the other concentration of oral gel three times daily......-effects. CONCLUSIONS: Topical capsaicin might be an alternative for the short-term treatment of BMS. However, further studies are needed to investigate especially the gastro-intestinal side-effects which may limit its long-term use....
Zanuzzo, Felipe S; Teixeira-Neto, Francisco J; Teixeira, Lívia R; Diniz, Miriely S; Souza, Vivian L; Thomazini, Camila M; Steagall, Paulo V M
The analgesic and antihyperalgesic effects of dipyrone, meloxicam or a dipyrone-meloxicam combination were compared in dogs undergoing elective ovariohysterectomy. In a double-blinded, prospective, randomised design, 40 bitches premedicated with intramuscular pethidine (4 mg/kg) and anaesthetised with isoflurane received one of four intravenous treatments (n = 10 per group) before ovariohysterectomy: control (physiological saline), meloxicam (0.2 mg/kg), dipyrone (25 mg/kg) or dipyrone-meloxicam (25 mg/kg and 0.2 mg/kg, respectively). Glasgow composite measure pain scale (GCMPS) and mechanical nociceptive thresholds (MNT) were assessed before anaesthesia and at 1, 2, 3, 4, 6, 8, 12 and 24 h postoperatively. Rescue analgesia (0.5 mg/kg morphine) was administered intramuscularly if the GCMPS was ≥3. The GCMPS and MNT did not differ among groups. The frequency of rescue analgesia was significantly (P meloxicam (70%) or dipyrone-meloxicam (40%). There was a significant reduction in the total number of rescue treatments in the dypyrone (n = 5) and dipyrone-meloxicam (n = 5) groups when compared with the control (n = 17) and meloxicam (n = 19) groups. Meloxicam and dipyrone-meloxicam significantly reduced the percentage of animals exhibiting severe pain during MNT measurements (30% and 0%, respectively) compared with the control group (50%). Dipyrone produced superior analgesia (reduced morphine consumption), while meloxicam produced better antihyperalgesia (fewer episodes of severe pain) in contrast to controls. When used in tandem, the beneficial effects were combined. Copyright © 2015 Elsevier Ltd. All rights reserved.
Kwon, Sunoh; Lee, Yangseok; Park, Hi-Joon; Hahm, Dae-Hyun
Biomechanical phenomenon called "needle grasp" through the winding of connective tissue has been proposed as an action mechanism of acupuncture manipulation. The aim of the present study is to verify whether the needle grasp force affects the pain-relieving activity of acupuncture in the tail-flick latency (TFL) and the rat paw formalin tests. In order to make different roughness on the acupuncture needle surface, the needles with 0.2 mm-diameter were scratched using silicon carbide sandpapers with the grit numbers of 600 (mild coarse) and 200 (extra coarse). The surface roughness and rotation-induced torque of the scratched needles were then measured by atomic force microscope and Acusensor®, respectively. Rat abdominal wall tissues including insertion site of acupuncture needle were excised after 5 unidirectional rotations of the needles having various degrees of roughness, and the morphological changes of connective tissues were analyzed using hematoxylin and eosin (H-E) staining. Finally, the effects of coarse needle surface on anti-nociception induced by twirling manipulation were tested in rat TFL and formalin test. It was observed that the rougher the needle surface, the stronger the needle grasp force and thickness of subcutaneous connective tissue while rotating. TFL increased in proportion to surface roughness of the ground needles 10 min after acupuncture into the Zusanli acupoint (ST36) on rat's legs. In the rat formalin test, the rougher needle also significantly exerted the larger analgesic effect during both early and late phases compared to non-ground normal needle. Surface roughness of the acupuncture needle enhanced an anti-nociceptive activity of acupuncture therapy in rats, which partially supports the mechanical signaling theory through connective tissues in acupuncture manipulation.
Shirvani, Armin; Shamszadeh, Sayna; Eghbal, Mohammad Jafar; Marvasti, Laleh Alim; Asgary, Saeed
The objectives of this study were to assess the efficacy of preemptive oral administration of single dose of non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the local anesthetic success in adults with irreversible pulpitis and to find the possible covariates that could predict treatment effect. A systematic search using electronic databases up to March 2015 was conducted. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated using random and fixed-effect inverse variance method. Subgroup and meta-regression analyses were conducted to assess the potential source of heterogeneity. Results showed that preemptive analgesics are more effective than placebo in increasing anesthetic success (OR = 0.30, CI% 0.24-0.39, p = 0.000) [Q = 55.860 (p = 0.001)]. In the subgroup analysis, administration of NSAIDs as monotherapy, ibuprofen as mono- vs. combination therapy, oxicam type drugs as monotherapy, and acetaminophen as combination therapy were significantly more effective in increasing anesthetic success OR = 0.25, CI% 0.16-0.38, p = 0.00, Q = 40.539 (p = 0.003); OR = 0.44, CI% 0.26-0.75, p = 0.00, Q = 12.833 (p = 0.011); OR = 0.48, CI% 0.30-0.74, p = 0.002, Q = 15.898 (p = 0.14); OR = 0.30, CI% 0.16-0.38, p = 0.001, Q = 7.506 (p = 0.02); OR = 0.10, CI% 0.16 0.38, p = 0.001, Q = 5.075 (p = 0.07), respectively. However, there was no significant difference in increasing anesthetic success between treatment and placebo arms when acetaminophen was administrated alone. In meta-regression analysis, an association between different types of NSAIDs (indomethacin, diclofenac potassium, and oxicam-type drugs) and articaine with treatment effect was observed. The administration of preemptive analgesics can induce superior intraoperative analgesia for patients with irreversible pulpitis. However, strategies such as co-administration of certain types of analgesics and anesthetic solution might be predictors
Full Text Available Background: Different Tanacetum species have been widely used in traditional medicine as a remedy for the pain and inflammation since ancient times. Because of the few studies conducted on the mechanism of Tanacetum parthenium (TP, this study has been conducted to determine the effects of TP on pain relief and its action mechanism. Materials and Methods: In this experimental study, 100 male mice (25-35 g were randomly grouped into receivers of distilled water, morphine (0.5 mg/kg, ibuprofen (100 mg/kg, different doses of the extract including 10, 20, 30 and 40 mg/kg of the extract. In order to study the pain relief effect of this herb, two groups were also received naloxon (0.5 mg/kg and naloxon together with the 40 mg/kg of the extract. Animals were injected with 0.9% acetic acid for visceral pain induction. 15 minutes after each injection antinociceptive effects were recorded by counting the number of writhes for 30 minutes. Achieved data were analyzed by SPSS statistical software, Kruskal-Wallis and Dunn post hoc test.Results: 40 mg/kg of the extract of TP caused a significant reduction in the pain response. Group receiving a dose of 40 mg/kg extract had higher antinociceptive effects than the group receiving ibuprofen (p<0.001 but it didn't have any significant difference with the group receiving morphine. Group receiving naloxone had a statistical significant difference with the group receiving 40 mg/kg extract with naloxone and the group receiving 40 mg/kg extract (p<0.001.Conclusion: Antinociceptive activity of TP extract is due to the activation of opioid system, however further studies are needed to be conducted for finding out the suitable position or the role of the antispasmodic effect of TP.
Aslaniants, Zh K; Melik-Eganov, G R; Evstratov, A V; Ivanov, M P; Batrakov, S G; Korobov, N V; Iasnetsov, V V
The protein fraction isolated from blood of seal, Phoca groenlandica, has been found to produce hyperalgesic effect on rats exposed to thermic or electrocutaneous nociceptive stimulation, but fail to affect writhes provoked by intraperitoneal injection of acetic acid solution on mice. When combined with morphine, the fraction lowered completely its narcotic analgetic action in the above mentioned tests. On the contrary, these same proteins combined with promedol or fentanil enhanced and prolonged analgetic effect of the latter. Tested in vitro the protein showed neither opioid nor anti-opioid activity. Therefore it is reasonable to suppose that neurophysiological activity of the isolated fraction is due to the peptides formed on enzymatic hydrolysis of proteins in vivo rather than these proteins as such.
Chen, Jun; Wang, Xuan; Qu, Yan-Ge; Chen, Zhi-Peng; Cai, Hao; Liu, Xiao; Xu, Fei; Lu, Tu-Lin; Cai, Bao-Chang
Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folk medicine for improving blood circulation, relieving rheumatic pain, reducing swelling and treating cancer. This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration. Most strychnine was removed from TAF and the resulted modified total alkaloid fraction (MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesic and anti-inflammatory activity of TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared. In contrast to TAF, most strychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showed significant analgesic activity in all the chemical-, thermal- and physical- induced nociception models, which indicated the presence of both centrally and peripherally mediated activities. MTAF also showed significant anti-inflammatory activity against xylene-induced ear edema. But TAF and strychnine demonstrated little activity in all those pharmacological tests. Brucine showed to be effective in acetic acid-induced writhing and xylene-induced ear edema test. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration. The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. The relatively higher pharmacological activity of MTAF compared to brucine
Evaluation of the analgesic, anti-inflammatory, anti-oxidant, phytochemical and toxicological properties of the methanolic leaf extract of commercially processed Moringa oleifera in some laboratory animals.
Adedapo, Adeolu Alex; Falayi, Olufunke Olubunmi; Oyagbemi, Ademola Adetokunbo
Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. The commercially processed M. oleifera was extracted using methanol as its solvent. Phytochemical analysis as well as the anti-oxidant properties of this supplement were also investigated. Acute toxicity was carried out in fasted mice. Carrageenan and histamine tests were used to assess anti-inflammatory effects in rats, while analgesic activities were assessed using the acetic acid-induced writhing test and formalin-induced paw lick test in mice. In the anti-oxidant tests, 1,1-diphenyl-2-picrylhydrazyl, ferrous reducing activity power, 2,21-azinobis-(3-ethylbenthialozine)-6-sulphonic acid and total polyphenolic (TPP) assays were deployed at concentrations of 10 mg/mL and 20 mg/mL. The phytochemical analysis showed that the extract contained flavonoids, terpenoids, glycosides, tannins and saponins. In the acetic acid-induced writhing test, the extract significantly reduced the number of writhes at 100 and 200 mg/kg but not so much at 50 mg/kg. In the formalin-induced paw lick test, the effect was similar to that of the acetic writhing test. The analgesic effects were comparable to that of indomethacin used at 10 mg/kg. In the anti-inflammatory test, the extract reduced the formation of oedema especially at a dose of 200 mg/kg. In the anti-oxidant test, the extract was found to possess a free radical-scavenging property and is concentration related. The use of this extract for medicinal and nutritional purposes may have thus been justified; however, caution must be exercised in its use to prevent the toxic effect.
Niki, Yuriko; Kanai, Akifumi; Hoshi, Keika; Okamoto, Hirotsugu
Trigeminal nerve block is widely used for trigeminal neuralgia (TN), though with much painful procedure and potential serious complications. The pain of TN occurs most frequently in the second and the third divisions of the trigeminal nerve, which are distributed in intraoral mucous membrane as well as face skin. Here, we examined the response to intraoral application of 8% lidocaine (LDC) in patients with oral TN pain in a double-blind, placebo (PBO)-controlled crossover study. Twenty-four outpatients with oral TN pain were randomized to receive intraoral application of either 8% LDC or saline PBO to the painful area. Following 7-days period, patients were crossed over to receive the alternative treatment. The pain was assessed with a numerical rating scale (NRS) before and 15 minutes after treatment. Patients used a descriptive scale to grade pain outcome and were asked to note any recurrence and the latency for recurrence after therapy. Intraoral LDC, but not PBO, significantly decreased the NRS from 5 (4, 8) (median [25, 75 percentiles]) to 1 (0, 4) (P = 0.001). Of the 24 patients, 19 described marked or moderate relief of pain after LDC but only three described the same after PBO application. The effect of LDC and PBO persisted for 2.8 (0.3, 3.0) and 0 (0, 0) hours, respectively. Intraoral application of 8% LDC produced prompt analgesia without serious side effects in patients with TN who presented with severe intraoral pain. Wiley Periodicals, Inc.
Full Text Available Xiaoming Liu, Hongjun Liu, Lihua Dai, Bingjie Ma, Ke Ma Pain Management Center, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: Chemokine CXCL12 and its receptor CXCR4 have been reported to play a critical role in neurogenesis and neuronal differentiation. Recently, some reports have implicated this chemokine signaling in the pathogenesis of many kinds of pain. However, its role in neuropathic pain (NP is still largely unclear. This study explored the distribution and function of CXCR4 in spinal cord (SC dorsal horn (DH in a rat L5 spinal nerve ligation (SNL model. Methods: Rats received repeated intrathecal injection of CXCR4 antagonist AMD3100. Behavioral assessments were conducted using a traditional “up–down” method. The spinal CXCL12 contents were measured by enzyme linked immunosorbent assay. The expression and distribution of CXCR4 in the SC were determined by immunoflurescence and Western blot. GlyRα3 expressions were also measured by Western blot or immunofluorescence. Results: SNL induced CXCL12–CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (P<0.01. CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (P<0.01 vs the SNL group on Day 14 and Day 21. Conclusion: CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP. Keywords: neuropathic pain, CXCL12, CXCR4, GlyRα3, L5 spinal nerve ligation
Somberg, John C; Molnar, Janos
Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 ± 1.65 (37%) with Cream I (from 8.44 ± 1.19 to 5.33 ± 2.0, P Cream II (from 8.42 ± 1.27 to 5.50 ± 1.96, P Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren gel (P creams, which were effective and provided pain relief in the majority of the patients studied.
Wu, Long-Jun; Xu, Hui; Ko, Shanelle W; Yoshimura, Megumu; Zhuo, Min
Substance P (SP) is a neuropeptide well known for its contribution to pain transmission in the spinal cord, however, less is known about the possible modulatory effects of SP. A new study by Gu and colleagues, published in Molecular Pain (2005, 1:20), describes its potential role in feed-forward inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition seems to function through a direct excitation of GABAergic interneurons by substance P released from primary afferent fibers and has a distinct temporal phase of action from the well-described glutamate-dependent feed-forward inhibition. It is believed that through this inhibition, substance P can balance nociceptive output from the spinal cord. PMID:16297242
Full Text Available Abstract Substance P (SP is a neuropeptide well known for its contribution to pain transmission in the spinal cord, however, less is known about the possible modulatory effects of SP. A new study by Gu and colleagues, published in Molecular Pain (2005, 1:20, describes its potential role in feed-forward inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition seems to function through a direct excitation of GABAergic interneurons by substance P released from primary afferent fibers and has a distinct temporal phase of action from the well-described glutamate-dependent feed-forward inhibition. It is believed that through this inhibition, substance P can balance nociceptive output from the spinal cord.
Lunn, Troels H; Frokjaer, Vibe G.; Hansen, Torben B
has not previously been investigated. The authors hypothesized that perioperative escitalopram would reduce pain after TKA in high pain catastrophizing patients. METHODS: A total of 120 pain catastrophizing patients (selected using the pain catastrophizing scale as preoperative screening tool......-defined mobilizations and at rest from 2 to 48 h and from days 2 to 6, morphine equivalents, anxiety, depression, and side effects. RESULTS: Pain upon ambulation (mean [95% CI]) 24 h after surgery in the escitalopram versus placebo group was 58 (53 to 64) versus 64 (58 to 69), the mean difference being -5 (-13 to 3), P...... in the escitalopram group. No other between-group differences were observed. CONCLUSIONS: Escitalopram did not reduce pain upon ambulation 24 h after TKA in high pain catastrophizing patients. Future studies on optimal timing, dose, and duration of selective serotonin reuptake inhibitor treatment might be warranted....
Full Text Available Objective: In our study, we aimed to compare epidural morphine and fentanyl analgesia and the side effects in post-thoracotomy pain management. Material and Methods: Forty patients, planned for elective thoracotomy were included. Bupivacain- morphine was administered through an epidural catheter to the patients in Group-M while bupivacain-fentanyl was given in Group-F. Pain assessment was carried out with the Visual Analogue Scale (VAS and VAS-I and VAS-II were assessed in 0, 4, 16 and 24th hour in the postoperative unit. Adverse effects were recorded after the 24th hour. Statistical analyses were performed by using Two-sample independent-t test, Mann Whitney-U test, Wilcoxon-signed ranks test and Pearson chi-squared tests. Results: Although, the VAS-I and VAS-II scores were lower in Group-M than Group-F, the difference was not significant statistically (p>0.05. When other hours were compared with initial states, beginning from the 4th hour, in both groups there was a statistically significant drop in VAS-I and VAS-II scores at all times (p<0.001. Comparing the complications between the groups, in Group-M nausea-vomiting (p<0.015 and bradycardia (p<0.012 were found significantly more frequently than in Group-F. Conclusion: We concluded that, in pain management after thoracic surgery, either morphine or fentanyl may be chosen in thoracal epidural analgesia but, especially in the early postoperative hours, close follow-up is necessary due to the risk of bradycardia development.
Perniola, Andrea; Magnuson, Anders; Axelsson, Kjell; Gupta, Anil
It remains unclear whether analgesia from intraperitoneal local anesthetics is via local or central mechanisms. This double-blind clinical trial tests the hypothesis that intraperitoneal local anesthetic is superior to continuous IV infusion for pain management. Primary outcome was morphine consumption during 0 to 24 h. Informed consent was obtained from 60 patients, age 30 to 75 yr, American Society of Anesthesiologists physical status I to II, undergoing abdominal hysterectomy. A computer-generated program randomized patients in parallel arms to group IV: continuous infusion of lidocaine 50 mg/h (10 ml) IV and saline 10 ml/h intermittently intraperitoneal; group IP: injection of lidocaine 50 mg/h (10 ml) once every hour intraperitoneally and continuous infusion of saline 10 ml/h intravenously; and group P (placebo): saline 10 ml/h both intravenously and intermittent intraperitoneal injection. Postoperative morphine consumption, pain intensity, recovery, home discharge, and lidocaine concentrations were measured. Morphine consumption during 0 to 24 h was lower in group IP versus group IV, mean difference -22.6 mg (95% CI, 11.4 to 33.8; P lidocaine in group IP was significantly lower than group IV, 0 to 4.5 h postoperatively (P = 0.03) with no evidence of systemic toxicity. Pain intensity and other recovery parameters were similar between the groups. The lower supplemental morphine consumption and plasma lidocaine concentration in group IP would confirm that the effects of local anesthetics are likely to be predominant via local intraperitoneal receptors or anti-inflammatory effects and not via central mechanisms alone.
Tamagaki, Shinji; Suzuki, Takahiro; Hagihira, Satoshi; Hayashi, Yukio; Mashimo, Takashi
It has been reported that the effect of intrathecally administered α2 adrenergic receptor (α2 AR) agonists is enhanced in mice that are chronically tolerant to systemic morphine. However, contributory factors have not been identified. Here we examined whether repeated systemic morphine affected the analgesic potency of intrathecal dexmedetomidine and the expression of subtype A, B and C α2 AR (α2A, α2B and α2C AR) in the dorsal root ganglion and dorsal horn in mice. After subcutaneous injection of morphine or saline for two weeks, dexmedetomidine was administered intrathecally to evaluate its antinociceptive effect. Also, the α2 AR subtypes and µ-opioid receptor mRNA expression in lumbar dorsal root ganglion was quantified using PCR, and α2A and α2C AR in lumbar dorsal root ganglion and dorsal horn were examined by immunohistochemistry. Daily morphine enhanced the antinociceptive effect of intrathecal dexmedetomidine, increased all the α2 AR subtypes but decreased the µ-opioid receptor mRNA expression in dorsal root ganglion and increased immunoreactivity of α2A and α2C AR in dorsal root ganglion and dorsal horn. These results suggest that systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of the α2A, α2B and α2C AR in lumbar dorsal root ganglion and dorsal horn. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.
Marzok, Mohamed A; El-khodery, Sabry A
To compare anti-nociceptive and sedative effects of tramadol, a combination of tramadol-lidocaine, and lidocaine alone for perineal analgesia in donkeys. Experimental 'blinded' randomized cross-over study. Six healthy adult donkeys. Treatments were tramadol (TR) (1.0 mg kg(-1) ), tramadol-lidocaine (TRLD) (0.5 and 0.2 mg kg(-1) respectively) and lidocaine (LD) (0.4 mg kg(-1) ) given into the epidural space. The volume of all treatments was 0.02 mL kg(-1) . Nociception was tested at the perineal region by pin prick, followed, if no reaction, by pressure from a haemostat clamp. Times to onset, degree and duration of anti-nociception of the perineal region were recorded. Response was tested immediately after drug administration and at: 2, 5, 10, 15, 30, 45, and 60 minutes post-administration and then at 30 minute intervals thereafter until a response re-occurred. Physiologic data and degree of sedation and ataxia were recorded pre-administration and at intervals for 240 minutes post-administration. Results were analyzed using anova, Kruskal-Wallis tests, and Wilks' Lambda test as relevant. Significance was taken as p < 0.05. Times (minutes, mean ± SD) to onset and duration of anti-nociception, respectively were; TR 13 ± 1.6 and 220 ± 4.6; TRLD 6 ± 0.8 and 180 ± 8.5; LD 4 ± 1.4 and 75 ± 4. Onset and duration times were significantly longer with TR than the other two treatments. TR never produced complete anti-nociception, whereas the TRLD and LD induced complete anti-nociceptive effects. Duration was significantly longer with TRLD than with LD alone. Epidural injections of TR and TRLD induced mild sedation. Epidural combination of TRLD produced an anti-nociceptive effect in the perineum, which was rapid in onset and had a longer duration of action than LD alone. An epidural single dose of TRLD combination would appear to provide an acceptable analgesic effect in the perineal region of donkeys. © 2014 Association of Veterinary
Full Text Available Humans have a long hystory of stimulating and mind-altering substances use. Depressive drugs, including morphine and other narcotics, barbiturates and ethanol, are strongly addictive for susceptible individuals. The phenomenon is most striking in the case of opiates. Morphine is an alkaloid of opium. Named after the Roman god of dreams, Morpheus, the compound has potent analgesic properties toward all types of pain. By supstitution of two hydroxylic groups of morphine many natural and semysyntetic derivatives with different pharmacological activity and analgesic action are obtained. Determinations and quantifications of narcotic analgesics in drug addicts are important in forensic medicine and clinical toxicology. With development of highly sensitive chromatography technique (HPLC-GC, GH-MS, more and more substances are determined, including opioid drugs: morphine, codeine, dyhydrocodeine, and heroin and 6-monoacetyl morphine. Hair analysys by HPLC/MS spectroscopy is an effective forensic tool for determining the use of abused drugs. The “fingerprint” for heroin in the mixture with the other substances(1-10 components is determined by 1D-TOCSY NMR.
Full Text Available Liliane J Dableh, James L HenryDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, CanadaAbstract: Chronic neuropathic pain that may arise from various nerve injuries or insults remains notoriously difficult to manage. The neuronal isoform of the enzyme nitric oxide synthase (nNOS has been shown to be involved in the spinal transmission of nociception in animal models of chronic pain. The aim of this study is to evaluate the effect of single dose and repeated administration of a selective nNOS inhibitor. Rats were unilaterally implanted with a 2-mm polyethylene cuff around the sciatic nerve. Paw withdrawal thresholds were measured using von Frey filament stimulation. Rats were given 10, 20, or 30 mg/kg of 7-nitroindazole (7-NI, or vehicle, on days 2, 5, and 7 after model induction, respectively. Paw withdrawal thresholds were measured before and at 30 and 60 min after injection. 7-NI significantly increased paw withdrawal thresholds at 60 min at the 20 and 30 mg/kg dosages. In the second part of this study, rats were given 20 mg/kg 7-NI daily for five days starting immediately after cuff implantation (days 0 to 4, and the cuff was removed on day 4. Withdrawal thresholds were measured intermittently over a 24-day observation period. No differences in withdrawal thresholds were observed between drug and vehicle-treated rats. Therefore, early and repeated administration of 7-NI did not affect the development or progression of the model. In conclusion, inhibition of nNOS had an analgesic but not a pre-emptive effect in this model of peripheral neuropathic pain.Keywords: neuronal nitric oxide synthase, nitric oxide, 7-nitroindazole, neuropathic pain, peripheral nerve injury, nociception
Further Evaluation of Delta Opioid Agonists as Candidate Adjuncts to Mu Opioid Analgesics: A Comparison of Interactions between Fentanyl and either Ketamine or the Delta Agonist SNC162 in Rhesus Monkeys
Banks, Matthew L.; Folk, John E.; Rice, Kenner C.; Negus, S. Stevens
Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine +fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu
Harton, Lisa R; Richardson, Janell R; Armendariz, Alexander; Nazarian, Arbi
Sex differences in the analgesic effects of morphine have been previously reported in various models that represent the sensory component of pain. However, pain sensation is a complex process that consists of both sensory and affective components. It is presently unclear whether the analgesic effects of morphine between the sensory and affective components of pain are sexually dimorphic. Moreover, differences in morphine dose-response in the two components of pain have not been examined in male and female rats. Therefore, we examined the analgesic effects of morphine on the sensory and affective components of formalin-induced pain behaviors in male and female rats. To discern the sensory component, rats were pretreated with varying doses of morphine and then intraplantar formalin-induced paw flinches were measured. Morphine reduced the number of formalin-induced paw flinches at a treatment dose of 4.0mg/kg. Morphine analgesia was similar across the sexes in the early (phase 1) and late phase (phase 2) of the formalin test. To examine the affective component, rats were pretreated with varying doses of morphine, and then intraplantar formalin-induced conditioned place aversion (CPA) was examined. Formalin produced CPA, which was blocked by morphine at doses of 1.0mg/kg and higher in male and female rats. Lastly, formalin-induced cFos expression and the effects of systemic morphine were examined in the superficial dorsal horn of the spinal cord. Intraplantar formalin produced robust expression of cFos; however, morphine did not attenuate the cFos expression. These results demonstrate a notable dissociation of the analgesic effects of morphine by detecting a fourfold shift in the minimum effective dose between the sensory and affective components of formalin-induced spontaneous pain, that were similar between male and female rats. The findings further suggest disparate mechanisms involved in systemic morphine-induced analgesia in the two components of formalin
Hunt, James R; Grint, Nicola J; Taylor, Polly M; Murrell, Joanna C
To evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery. Prospective, randomized, blinded clinical study. Forty dogs and 48 cats. Animals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg(-1) with either dexmedetomidine (dex) 250 μg m(-2) or acepromazine (acp) 0.03 mg kg(-1), followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall-Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005). Cats premedicated with dex were more sedated than cats premedicated with acp (p buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia. A combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent. © 2012 The Authors. Veterinary Anaesthesia and Analgesia © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Holsgaard-Larsen, A; Clausen, B; Søndergaard, J
OBJECTIVE: To investigate the effect of a NEuro-Muscular EXercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis. We hypothesized that knee joint...... loading during walking would be reduced by NEMEX and potentially increased by PHARMA. DESIGN: Single-blind, RCT comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee osteoarthritis were randomly allocated (1:1) to one of two 8-week treatments...
Keppel Hesselink JM
Full Text Available Jan M Keppel Hesselink Department of Pharmacology, University of Witten/Herdecke, Witten, Germany Abstract: The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957–1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. Keywords: palmitoylethanolamide, sociology, science, paradigm, peroxisome proliferator-activated receptor-alpha, nutraceutical
Sertié, J A A; Woisky, R G; Wiezel, G; Rodrigues, M
Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.
Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.
Full Text Available The effects of the ethanol and dichloromethane extracts from the pericarp of Garcinia mangostana Linn.(G. mangostana on nociceptive response using writhing and hot plate tests in mice and the antipyretic activity in yeastinduced fever in rats, were examined. Anti-inflammatory activity using carrageenin-induced paw edema in rats was also investigated. The ethanol extract (400, 800 mg/kg, p.o. significantly suppressed the writhings induced by acetic acid. The dichloromethane extract (200, 400 and 800 mg/kg, p.o. also decreased acetic acid-induced writhing in mice. Neither theethanol extract nor dichloromethane extract had significant effects on antinociceptive response in the hot plate test. No significanteffects on yeast-induced fever were observed after oral administration of the ethanol and dichloromethane extractsin rats. Either oral administration (800 mg/kg of the ethanol extract or dichloromethane extract significantly decreased therat paw edema induced by carrageenin. These results suggest that the ethanol and dichloromethane extracts from the fruithull of G. mangostana possess analgesic and anti-inflammatory actions but no antipyretic action and one mechanism of action of the anti-inflammatory activity of the extracts may involve in cyclooxygenase (COX inhibition.
Full Text Available Delta (DOR and mu opioid receptors (MOR can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED50 for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED50 had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment.
Isabela Ciniello Araujo
Full Text Available O propofol é um agente anestésico intravenoso usado para indução e manutenção da anestesia, mas produz analgesia limitada, havendo a necessidade do uso concomitante de analgésicos. Avaliou-se o efeito analgésico do butorfanol na dor somática em gatos anestesiados com doses fracionadas de propofol. Foram utilizados 16 animais, distribuídos aleatoriamente em dois grupos. Os animais do grupo controle foram pré-tratados com 0,2mg/kg de acepromazina por via IM e, após 15 minutos, receberam 6mg/kg de propofol por via IV. Os animais do grupo tratamento foram pré-medicados com uma combinação de acepromazina (0,2mg/kg e butorfanol (0,8mg/kg, administrados na mesma seringa por via IM, e, após 15 minutos, receberam 6mg/kg de propofol por via IV. Em ambos os grupos, a manutenção da anestesia foi feita com administrações de propofol, na dose de 3mg/kg, por via IV, sempre que necessário, durante 60 minutos. A necessidade de readministração de propofol foi verificada pela resposta apresentada ao pinçamento cutâneo, através de uma pinça de Kocher. Avaliaram-se também as freqüências cardíaca e respiratória, pressão arterial média, saturação de oxiemoglobina e temperatura retal. A administração de butorfanol causou apenas redução nas freqüências cardíaca e respiratória e na saturação de oxiemoglobina, em comparação com o grupo controle,sem exercer influência significativa sobre o período hábil, a dose total administrada e o período de recuperação do propofol. Concluiu-se que a adição de butorfanol não produziu analgesia somática em gatos anestesiados com doses fracionadas de propofol.Propofol is an intravenous anesthetic agent used for induction and maintenance of anesthesia but produces limited analgesia, and concomitant use of analgesics is necessary. The analgesic effect of butorphanol in somatic pain in cats anesthetized with intermittent doses of propofol was evaluated. Sixteen animals were randomly
Wang, Yong-Jie; Zuo, Zhen-Xing; Zhang, Mei; Feng, Zhi-Hui; Yan, Min; Li, Xiang-Yao
Both pharmacologic and genetic approaches have been used to study the involvement of the muscarinic acetylcholine system in the regulation of chronic pain. Previous studies suggest that the M2 and M4 subtypes of muscarinic acetylcholine receptors (mAChRs) are important targets for the development of chronic pain. (5R,6R)6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1] octane (PTAC) has agonist effects on muscarinic M2 and M4 receptors and antagonist effects on muscarinic M1, M3, and M5 receptors. However, its analgesic effects have been less studied. Male C57B L/6 mice were anesthetized, and left common peroneal nerve (CPN) ligation was performed to induce neuropathic pain. Before and after the application of PTAC systemically or specifically to the anterior cingulate cortex (ACC), the withdrawal thresholds to mechanical stimulation and static weight balance were measured, and the effects of PTAC on the conditioned place preference (CPP) were further evaluated. Western blotting was used to examine the expression of M1 and M2 in the striatum, ACC, and ventral tegmental area. The application of PTAC ([i.p.] intraperitoneal injection) increased the paw withdraw threshold in both the early (0.05 mg/kg, mean difference [95% confidence interval, CI]: 0.19 [0.05-0.32]; 0.10 mg/kg: mean difference [95% CI]: 0.34 [0.22-0.46]) and the late phases (0.05 mg/kg: mean difference [95% CI]: 0.45 [0.39-0.50]; 0.1 mg/kg: mean difference [95% CI]: 0.44 [0.37-0.51]) after nerve injury and rebalanced the weight distribution on the hind paws of mice (L/R ratio: before, 0.56 ± 0.03. 0.05 mg/kg, 1.00 ± 0.04, 0.10 mg/kg, 0.99 ± 0.03); however, it failed to induce place preference in the CPP (0.05 mg/kg, 2-way analysis of variance, P > .05; 0.2 mg/kg, 2-way analysis of variance, P > .05,). At the same doses, the analgesic effects at D3-5 lasted longer than the effects at D14-16. This may be due to the down-regulation of the M2 and M1 in tested brain regions. These observations
José Ferreira Sarmento-Neto
Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.
Treculia africana was claimed to be useful in the treatment of mental illness. The present work was carried out to evaluate the neurobiology and analgesic properties of Treculia africana in mice. The neurobiology and analgesic properties of Treculia africana was investigated by using head dip, elevated plus maze, Y-maze, ...
The analgesic activity of the water extracts (50,100 and150 mg/Kg body weight) of the root bark, stem bark, leaves, fruits and seeds of Carissa edulis were evaluated in mice using the mechanical method (tail-chip method) and chemical method (acetic acid induced writhing). The plant was found to have analgesic activity, ...
The acetic acid-induced writhing, formalin, and tail clip tests were used to evaluate analgesic activity while the 2,4-dinitrophenol (DNP)-, d-amphetamine-, and ... that the aqueous whole plant extract of Drymaria cordata possesses analgesic and antipyretic properties mediated through peripheral and central mechanisms.
This study evaluated the analgesic activity of the metabolic leaf extract of Jatropha curcas (Linn) in vivo using analgesic models viz: Hot plate method in mice, tail flick or immersion method in rat and acetic acid-induced writhing reflex model in mice. In all the models, acetylsalicylic acid (ASA) was used as the reference drug.
Passik, Steven D; Webster, Lynn
Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.
The analgesic and anti-inflammatory effects of the methanolic extract of the leaves of Jatropha curcas were investigated in mice and rats respectively. The phytochemical screening of the extract was also carried out. The analgesic effect was determined by acetic acid – induced writhing test in mice. While the anti- ...
Topical Analgesic Nanolipid Vesicles Formulation of Capsaicinoids Extract of Bhut Jolokia (Capsicum chinense Jacq): Pharmacodynamic Evaluation in Rat Models and Acceptability studies in Human Volunteers.
Sarwa, Khomendra Kumar; Mazumder, Bhaskar; Suresh, Preeti K; Kaur, Chanchal Deep
Capsicum fruit is used for treating skeletomuscular disorders as a counterirritant analgesic around the globe. But its concentration-dependent irritation and concomitant withdrawal of therapy by the patients hampers its therapeutic usefulness. In the present study, a novel nanolipid approach based on elastic phospholipid vesicles was employed to encapsulate a semipurified extract of Bhut Jolokia for topical drug delivery application. The working hypothesis was that encapsulation of irritant extract into nanolipid vesicles may prevent the initial rejection of formulation and the elastic vesicles may facilitate deeper skin penetration over a shorter time period. Surface response methodology was adopted to study the effect of selected independent formulation variables on dependent variables like vesicle size and entrapment efficacy. The prepared formulations were characterized for various physicochemical parameters. The efficacy of the newly developed nonolipid vesicle formulation loaded with semipurified extract of Bhut Jolokia was tested on carrageenan and formaldehyde-induced inflammation as well as Freund's adjuvant-induced arthritis model. The novel formulations were tested on human volunteers in a Phase I clinical trial and were found to be acceptable. The study indicates that this strategy holds immense potential for topical delivery of the bioactive from Bhut Jolokia and can pave the way for its clinical applications.
Avez-Couturier, Justine; Wood, Chantal
There are a number of different types of analgesics in paediatrics. They must be used in accordance with the situation, the type of pain and the characteristics of the child. In all cases, strict compliance with the posology and the instructions for use is essential to avoid any risk of error. Finally, pharmacological, physical and psychological treatments are employed in a complementary manner, for the biopsychosocial management of the child's care. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Malairajan, P; Geetha Gopalakrishnan; Narasimhan, S; Jessi Kala Veni, K
In the present study of some of the Indian medicinal plants Sida acuta whole plant (Malvaeae), Stylosanthes fruticosa (whole plant) (Papilionaceae), Toona ciliata (heart wood) (Meliaceao), Bougainvilla spectabilis (leaves) (Nyctaginaceae), Ficus glomerata (bark, leaves) (Moraceae) and Polyalthia longifolia (leaves) (Annonaceae). The different plants were used in folklore medicine in the treatment of toothache and strengthening of gums, anthelmintic, kidney diseases, analgesic, anti-inflammatory, hepatoprotective, antihyperglycaemic, antihyperglycaemic and anticancer. The extract was prepared using powdered material with ethanol, concentrated under vacuo and were evaluated for analgesic activity by analgesiometer at three dose level (100, 300 and 500mg/kg). Analgesic activity was significant with Toona ciliata (heart wood) ethanolic extract when compared with other extracts and its activity was confirmed by tail immersion method.
McDonnell, John G
The transversus abdominis plane (TAP) block is an effective method of providing postoperative analgesia in patients undergoing midline abdominal wall incisions. We evaluated its analgesic efficacy over the first 48 postoperative hours after cesarean delivery performed through a Pfannensteil incision, in a randomized controlled, double-blind, clinical trial.
The n-butanol leaf fraction of Vernonia glaberrima was evaluated for its toxicity, analgesic and anti-inflammatory effects. The leaves of V. glaberrima were collected, identified and extracted with methanol using maceration method and the resulting crude methanol extract was then partitioned using different solvents of ...
Full Text Available Freya Waddington, Mark Naunton, Jackson Thomas Faculty of Health, University of Canberra, Canberra, ACT, Australia Introduction: Analgesic nephropathy is a disease resulting from the frequent use of combinations of analgesic medications over many years, leading to significant impairment of renal function. The observation of a large number of cases of renal failure in patients abusing analgesic mixtures containing phenacetin led to the initial recognition of the nephrotoxicity from the use of analgesics. Phenacetin was subsequently exclusively blamed for this disease. However, the role of a single analgesic as a sole cause of analgesic nephropathy was challenged, and a number of researchers have since attempted to determine the extent of involvement of other analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs, aspirin, and paracetamol. Case presentation: We present the case of an 83-year-old woman with a history of NSAID-induced nephropathy with poor pain control and reluctance to use paracetamol. We attempt to briefly review the evidence of paracetamol being implicated in the development of analgesic-induced nephropathy. Conclusion: There is a lack of concrete data regarding causative analgesics, including paracetamol. Patients should therefore not be withheld paracetamol, an effective and commonly recommended agent, for fear of worsening renal function. Keywords: kidney, paracetamol, nephropathy, phenacetin
Boyer, Edward W; Wines, James D
Access to prescription opioid analgesics has made Internet pharmacies the object of increased regulatory scrutiny, but the effectiveness of regulatory changes in curtailing availability of opioid analgesics from online sources has been not assessed. As part of an ongoing investigation into the relationship between the Internet and substance abuse, we examined the availability of prescription opioid analgesics from online pharmacies. From a pharmacy watch Web site, we constructed a data set of postings entered every 3 months beginning November 1, 2005, that were related to the purchase of prescription opioid analgesics. Trained examiners assessed whether the final post described accessibility of pain medications that was increasing or decreasing. We identified 45 threads related to the availability of opioid analgesics from Internet pharmacies. Of the 41 (91%) threads describing the declining availability of opioid analgesic agents from Internet pharmacies, 34 (82%) received posts on November 1, 2007. Despite the subjective nature of the research question, there was high interobserver agreement between coders (kappa= .845) that availability of opioid analgesics from online pharmacies had decreased. This finding was supported by a dramatic rise in the number of pageviews (an accepted measure of Web site visitor interest in a page's content) of Web pages describing decreased availability of opioid analgesics. These data suggest striking decreases in the availability of prescription opioid analgesic pharmaceuticals. This self-reported change in drug availability may be related to increased regulation of and law enforcement operations directed against Internet pharmacies.
Staahl, Camilla; Drewes, Asbjørn Mohr
Treatment of pain is one of the major challenges in clinical medicine. However, it is often difficult to evaluate the effect of a treatment, as the many symptoms of the underlying diseases often confound this assessment. Furthermore, as the pain mechanisms in many diseases are poorly understood, the limited successful trial and error approach is most often used in the selection of analgesics. Hence, there is a need for new methods in the characterization and treatment of pain. Human experimental pain models offer the possibility to explore the pain system under controlled settings. The models can also be used to screen the analgesic profiles of drugs targeted to treat pain. This review gives a brief introduction to the methods used to evoke and assess pain in the skin, muscle and viscera. New methods using multimodal stimulation and activation of central pain mechanisms can to a higher degree mimic the clinical situation, and such methods are recommended in the future screening of analgesics. Examples of the use of experimental pain models in the testing of analgesics are given. With these models the therapeutic spectrum may be defined from a differentiated knowledge on the effect of drugs on the pain system. Such information may be used in the future guidelines for trials and clinical use of analgesics.
In CNS depressant test, diazepam (1 mg/kg) was used as reference drug while indomethacin (10 mg/kg) and loperamide(2 mg/kg) were used as standard drugs in analgesic and antidiarrheal tests, respectively. Results: In hole cross method, EALS showed the most effective depressant effect, viz, 1.17±0.17 for 200 mg/kg ...
Full Text Available Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK, a member of mitogen-activated protein kinase (MAPK family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS-induced phosphorylated JNK (pJNK expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.
Full Text Available Xiao Jing Wang, Sze H Wong, Roshan Givergis, Emil W Chynn Park Avenue LASEK, New York, NY, USA Background: To evaluate the analgesic efficacy of bromfenac sodium ophthalmic solution 0.09% compared with ketorolac tromethamine ophthalmic solution 0.5% in laser epithelial keratomileusis (LASEK or epithelial keratomileusis (epi-LASEK, sometimes referred to as epi-LASIK. Methods: Eighty eyes (from 40 patients, 18 men and 22 women undergoing bilateral simultaneous LASEK or epi-LASEK were randomized to receive ketorolac in one eye and bromfenac in the other. Mean age was 33.13 ± 9.34 years. One drop of bromfenac or ketorolac was instilled in each eye 15 minutes and one minute prior to surgery, and two and four hours following surgery. Patients were instructed to instill the medications on-label each day through postoperative day 4. The subjects completed pain and visual blurriness assessments from day of surgery to postoperative day 4. Uncorrected visual acuity was tested on postoperative days 1 and 6. Results: For each of the five days, pain scores for bromfenac-treated eyes were significantly less than that for ketorolac-treated eyes (P < 0.01. Of the 40 patients, 32 (80% said bromfenac provided better postoperative analgesia than ketorolac. There was no statistically significant difference in visual blurriness scores between the two groups (P > 0.1. Uncorrected visual acuity did not vary significantly between the treatment groups (P > 0.1. No serious adverse events were noted. Conclusion: Bromfenac is subjectively superior to ketorolac in reducing postoperative pain following LASEK or epi-LASEK. The subjects tolerated the drugs well with no serious adverse outcomes and no difference in uncorrected visual acuity. Keywords: LASEK, epi-LASEK, epi-LASIK, ketorolac, bromfenac, postoperative pain, nonsteroidal anti-inflammatory drugs
Our results provided evidence that saponins are implicated in the analgesic and anti-inflammatory effects observed in our earlier studies on the crude methanol extract of Ficus platyphylla stem bark, thus supporting the isolation and development of the saponin components of this medicinal plant as analgesics and ...
The non-opioid analgesics possess antipyretic and anti-inflammatory activity and thus are often employed for such purpose of controlling inflammation as well as antipyretic. The non-opioid analgesics are freely available devoid of causing dependence but their potential harmful effects can sometimes be serious. The need
Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan
Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953
Wiese, Ashley J; Muir, William W; Wittum, Thomas E
To estimate the prevalence and characteristics of pain in dogs and cats examined by an emergency service at a veterinary teaching hospital and evaluate the response of dogs and cats with signs of pain to analgesic treatment. Cross-sectional study. 317 dogs and 112 cats. A questionnaire was used to categorize the characteristics of pain. The location, cause, and signs of pain were determined by obtaining a thorough history and conducting a physical examination. Pain was categorized by type (superficial somatic, deep somatic, or visceral), mechanism (inflammatory, neuropathic, or both), severity (mild, moderate, or severe), and duration. Evidence for primary or secondary hypersensitivity and hyposensitivity to manipulation was determined. The response to single or multiple analgesic drug administration was assessed. 179 (56%) dogs and 60 (54%) cats had signs of pain. In most of these dogs and cats, pain was classified as acute (dogs had deep somatic pain; most cats had visceral pain. Inflammation was the most common mechanism. One hundred nineteen (66%) dogs and 41 (68%) cats were treated with analgesic drugs. Analgesic treatment was considered effective in 73 (61%) dogs and 31 (76%) cats. Results suggest that moderate to severe acute somatic pain caused by inflammation is common in dogs and cats examined by an emergency service and that a combination of multiple analgesic drugs is more effective than any single analgesic drug in the treatment of pain in these dogs and cats.
Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen
The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.
Abodola, M A; Lutfi, M F; Bakhiet, A O; Mohamed, A H
Prosopis chilensis is used locally in Sudan for inflammatory conditions of joints; however, literature lacks scientific evidence for anti-inflammatory effect of this plant. To evaluate anti-inflammatory and analgesic effects of prosopis chilenses. Edema inhibition percent (EI %) and hot plate method were used to evaluate anti-inflammatory and analgesic effects of Prosopis chilenses in Wistar albino rats. Anti-inflammatory and analgesic effects of Prosopis chilenses were compared to indomethacin and acetylsalicylic acid respectively. Ethanolic extract of prosopis chilensis at a dose of 200 and 100mg/kg body weight achieved peak EI% (EI% = 96.1%) and (EI% = 94.4%) three and four hours after oral dosing respectively. The maximum EI% for indomethacin was 97.0% and was recorded after 4 hours following oral administration of the drug at a dose of 5 mg/kg body weight. Prosopis chilensis extracts at doses of 100 and 200 mg/kg body weight significantly increased the rats' response time to hot plate compared to acetylsalicylic acid at a dose rate of 100mg/kg body weight (P<0.05). The current results suggest potential anti-inflammatory and analgesic effects of prosopis chilenses. Relevance of these effects to prosopis chilenses phy-to-constituents was discussed.
Andersen, Lasse Østergaard; Kehlet, H
In recent years, there has been an increasing interest in local infiltration analgesia (LIA) as a technique to control postoperative pain. We conducted a systematic review of randomized clinical trials investigating LIA for total knee arthroplasty (TKA) and total hip arthroplasty (THA) to evaluate...... were selected for inclusion in the review. In THA, no additional analgesic effect of LIA compared with placebo was reported in trials with low risk of bias when a multimodal analgesic regimen was administered perioperatively. Compared with intrathecal morphine and epidural analgesia, LIA was reported...... to have similar or improved analgesic efficacy. In TKA, most trials reported reduced pain and reduced opioid requirements with LIA compared with a control group treated with placebo/no injection. Compared with femoral nerve block, epidural or intrathecal morphine LIA provided similar or improved analgesia...
Ferda Yılmaz İnal
Full Text Available Aim: Although laparoscopic inguinal hernia (IH repair in adults is widely accepted, its advantages in pediatric age group are questionable. We aimed to compare the effects of open inguinal hernia repair and laparoscopic inguinal hernia repair on length of anaesthesia, postoperative pain and analgesic consumption in boys who underwent unilateral inguinal hernia repair. Methods: Forty patients aged between 7 and 14 years who underwent open and laparoscopic inguinal hernia repair were included in this study. The patients were randomly divided into two groups: unilateral open inguinal hernia repair group (OR n=20 and unilateral laparoscopic inguinal hernia repair group (LR n=20. All patients underwent general anesthesia. The duration of anaesthesia and the duration of surgery were recorded. The Patient Controlled Analgesia (PCA device was set at a 0.01 mg/kg bolus dose, 10 minutes lockout interval and 4 hour limit of 4 mg morphine. The patients, who received morphine PCA for 24 hours postoperatively, were monitored with continuous oximetry. The Visual Analogue Scale (VAS was used to measure pain (0 cm: no pain, 10 cm: worst possible pain. We recorded the side effects of morphine, such as respiratory depression, nausea, vomiting, urinary retention, pruritus. SpO2 level and Ramsay Sedation Scale (RSS, Numerical Rating Scale (NRS, and Visual Analogue Scale (VAS scores at intervals 1, 2, 4, 12, 24 hours as well as amount of analgesics consumed and number of requests within 24 hours postoperatively were recorded. Time to first walking was recorded. Results: In group OR, the mean duration of anaesthesia and surgery were 39.85 minutes and 28.85 minutes, respectively. In group LR, the mean duration of anaesthesia and surgery were 26.11 and 20.53 minutes, respectively. VAS scores and time to first walking were similar in both groups. There was no significant difference in amount of analgesics consumed and number of request between the two groups. In group OR
Venkata Kishan Pokuri
Conclusion: T. chebula significantly increased pain threshold and pain tolerance compared to placebo. Both the study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug in patients suffering from osteoarthritis, rheumatoid arthritis and other painful conditions.
Sah, Sangeeta Pilkhwal; Mathela, Chandra S; Chopra, Kanwaljit
Valeriana wallichii (Family Valerianaceae), popularly named as Indian valerian, exists as three chemotypes. Aim of the study was to evaluate the effect of V. wallichii chemotype (patchouli alcohol) extract (DCME) and essential oil (VPAEO) on experimental models of nociception and to elucidate its possible mechanism of action. Analgesic effect was evaluated using acetic acid induced writhing and tail flick model. DCME and VPAEO (40 and 80 mg/kg, p.o.) significantly inhibited the number of writhings as compared to vehicle treated group. None of the doses of DCME and VPAEO exhibited any effect in tail flick model suggesting only peripheral analgesic activity. When studied for mechanism of action in acetic acid induced writhing, subeffective dose of essential oil significantly potentiated the effect of aspirin while no potentiation was seen in case of extract. These data suggest that essential oil VPAEO exerted peripheral analgesic via inhibition of prostaglandin synthesis.
were compared with the standard drugs: aspirin. (100 mg/kg), paracetamol (100 mg/kg) and indomethacin (50 mg/kg) to determine the acetic- acid induced writhing response in mice. The extract concentrations and standard drugs were administered to seven groups of six mice per group. Extract Preparation. The leaves of ...
Full Text Available Neuropathic pain elevates spinal anandamide (AEA levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH, is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1 channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA and palmitoylethanolamide (PEA, and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX, and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats.
Thereza C. M. de Lima
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.
de Lima, T C; Morato, G S; Takahashi, R N
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.
Wang, Jing-Jie; Chen, Guang-Jun; Chen, Wen; Du, Jin; Luo, Ai-Lun; Huang, Yu-Guang
To examine the analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 (COX-2) in the spinal dorsal horn. Forty-eight Sprague-Dawley rats were equally divided into three groups: control group, sham-operated group, and zymosan group. According to Meller's method, zymosan (1.25 mg) was injected intraplantarly to induce paw inflammation in zymosan group; an equal volume of PBS was administered in the sham-operated group. Mechanical withdrawal threshold (MWT) and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine calpain activity in the spinal dorsal horn with Western blot analysis. Another sixty-four Sprague-Dawley rats were divided into three groups: sham-operated group, zymosan-induced paw inflammation with intraperitoneal dimethyl sulphoxide (DMSO) treatment group, and zymosan-induced paw inflammation with intraperitoneal calpain inhibitor ALLN treatment group. MWT and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine the COX-2 expression in the spinal dorsal horn with Western blot analysis. MWT significantly decreased in the rats with zymosan-induced paw inflammation, while the maximum thickness of paw significantly increased, compared with control and sham-operated rats (P horn was dramatically activated after zymosan injection (P horn compared with DMSO treatment (P effective to attenuate zymosan-induced paw inflammatory pain. Calpain activation may be one aspect of the signaling cascade that increases the COX-2 expression in the spinal cord and contributes to mechanical hyperalgesia after peripheral inflammatory injury.
Zeinab Ahmed Elseify
Full Text Available Background : Adequacy of postoperative analgesia is one of the most important factors that determine early hospital discharge and patients′ ability to resume their normal activities postoperatively. The optimal non-opioid analgesic technique for postoperative pain management would reduce pain and enhance patient satisfaction, and it also facilitates earlier mobilization and rehabilitation by reducing pain-related complications after surgery. The aim of this study was to evaluate the analgesic efficacy of intravenous paracetamol and parecoxib when used alone, or in combination. Methods : Sixty American Society of Anesthesiology (ASA physical status I and II adult patients who were scheduled for anterior cruciate ligament reconstruction were included in this study. Patients were allocated into three groups: group I patients received 1g intravenous paracetamol after induction and another 1 g 4 h later, group II received 40 mg parecoxib after induction, while group III received combination of both drugs (paracetamol 1 g and parecoxib 40 mg. Pain during rest and mobility was assessed in the immediate postoperative period, 2 h and 8 h successively using visual analog scale (VAS. Patient satisfaction was rated according to satisfaction score. Results : Total morphine requirements were lower in group III patients (6.9±2.7 mg in comparison to group I patients (12.6±3.6 mg or group II patients (9.8±2.8 mg. The least VAS scores were recorded during knee movement (3.8±1.1 in group III patients compared to group I (6.0±1.8 and group II patients (4.8±1.9. Eight hours postoperatively, group III patients were more satisfied regarding the postoperative pain management. Conclusion : Combination of intravenous paracetamol and parecoxib provided better analgesia and higher patient satisfaction than each drug when used separately.
Lucarini, Rodrigo; Bernardes, Wagner A; Ferreira, Daniele S; Tozatti, Marcos G; Furtado, Ricardo; Bastos, Jairo K; Pauletti, Patrícia M; Januário, Ana H; Silva, Márcio L Andrade E; Cunha, Wilson R
Despite several pharmacological applications of Rosmarinus officinalis L. (Lamiaceae), studies on its analgesic and anti-inflammatory properties have been scarce. The aim of this work was to use in vivo models to evaluate the analgesic and anti-inflammatory activities of the aqueous extracts obtained from leaves (AEL) and stems (AES) of Rosmarinus officinalis, as well as its isolated compound--rosmarinic acid (RA). We also prepared and assessed the acetyl ester derivative of RA. The analgesic activity was evaluated using abdominal constriction and formalin tests. For the evaluation of the anti-inflammatory effects, carrageenin-induced paw edema in rats were used. The extracts were used at doses of 100, 200 and 400 mg kg⁻¹ compounds were tested at 10, 20 and 40 mg kg⁻¹. Orally administered AEL, AES and RA were not significantly active at any of the doses tested during the abdominal constriction test; the acetyl ester derivative of RA displayed significant analgesic activity. In the carrageenin-induced paw edema assay, the acetyl derivative of RA at all the tested doses produced significant anti-inflammatory effects and reduced the number of paw licks in the second phase of the formalin test. The results suggest that the analgesic effects of the acetyl derivative of RA operate via a peripheral-mediated mechanism. The acetyl ester derivative of RA is potentially applicable as a new lead compound for the management of pain and inflammation.
Hou, Xinran; Weng, Yingqi; Ouyang, Bihan; Ding, Zhuofeng; Song, Zongbin; Zou, Wangyuan; Huang, Changsheng; Guo, Qulian
Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats. The analgesic effect of TSA was blocked by co-administration of CTAP, a specific MOR antagonist, confirming the involvement of mu-opioid receptor (MOR). A reduction of MOR expression was observed in the lumbar spinal cord of BCP rats and TSA treatment was able to partially reverse it. In vitro study in PC12 cells also demonstrated the dose-dependent enhancement of MOR expression by TSA treatment. Taking all into consideration, we could draw the conclusion that HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.
Kristensen, S; Schmidt, E B; Schlemmer, A; Rasmussen, C; Johansen, M B; Christensen, J H
This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA). Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end. In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B5 (p < 0.001) compared with controls. The n-3 PUFA-supplemented group showed improvement in outcome measures for disease activity, although the difference between the groups was not statistically significant. However, use of NSAIDs and paracetamol was significantly reduced in the n-3 PUFA group compared to the control group. Finally, there was a significant decrease in leukotriene B4 formation in the n-3 PUFA group compared with controls.
Zuo, Jian; Xia, Yan; Mao, Kun-Jun; Li, Xiang; Chen, Jian-Wei
Securidaca inappendiculata Hassk. is an traditional Chinese medicine curing rheumatoid arthritis, but there is a lack of reports on material base research. To find the active fraction of S. inappendiculata contributing the most to antirheumatic activity. Prior to assays in vivo, mice were treated with different fractions from S. inappendiculata for 5 d at doses relative to 10, 5, and 2.5 g/kg of crude drug. Hot plate test and carrageenan-induced paw edema test were used to investigate analgesic and anti-inflammatory activities. PGE2 levels in inflammatory paws were determined by a colorimetric method. Carbon clearance test in vivo and lymphocyte transformation test in vitro were employed to assess the immune regulation activity. HPLC was used to explore the main compounds in the active fraction. All the fractions, especially the dichloromethane fraction (SID), alleviated inflammation. High dose of SID (112 mg/kg) inhibited paw swelling by 63.1%, and decreased PGE2 level to 38 ng/mL. The ethyl acetate fraction (SIE) and SID suppressed the carbon clearance rate (K = 0.044, 0.038 for high dose) efficiently. All fractions hindered the transformation and proliferation of lymphocyte, and prolonged the reaction time of rats in the hot plate test. The concentrations of two typical xanthones: 2-hydroxyl-1,7-dimethoxyl-xanthone and 1,7-dihydroxyl-xanthone in SID were 0.93% and 1.19%, respectively, by HPLC analysis. SID exhibited significant anti-inflammatory, analgesic, and immunodepressive effects in vivo and vitro, and deemed as the main material base for the antirheumatic activity.
Box jellyfish (Carybdea alata) in Waikiki. The analgesic effect of sting-aid, Adolph's meat tenderizer and fresh water on their stings: a double-blinded, randomized, placebo-controlled clinical trial.
Thomas, C S; Scott, S A; Galanis, D J; Goto, R S
The study measured the analgesic effects of three popular Hawaii remedies for stings from the box jellyfish, Carybdea alata. Analysis of data showed that aerosol sprays of Sting-Aid (an aluminum sulfate solution), Aldolph's meat tenderizer dissolved in water, and fresh water neither increased nor decreased the pain of box jellyfish stings more than the control (seawater).
Stiglitz, D K; Amaratunge, L N; Konstantatos, A H; Lindholm, D E
Preventive analgesia is defined as the persistence of the analgesic effects of a drug beyond the clinical activity of the drug. The N-methyl D-aspartate receptor plays a critical role in the sensitisation of pain pathways induced by injury. Nitrous oxide inhibits excitatory N-methyl D-aspartate sensitive glutamate receptors. The objective of our study was to test the efficacy of nitrous oxide as a preventive analgesic. We conducted a retrospective analysis of data from a subset of patients (n = 100) randomly selected from a previous major multicentre randomised controlled trial on nitrous oxide (ENIGMA trial). Data analysed included postoperative analgesic requirements, pain scores and duration of patient-controlled analgesia during the first 72 postoperative hours. There was no significant difference in postoperative oral morphine equivalent usage (nitrous group 248 mg, no nitrous group 289 mg, mean difference -43 mg, 95% confidence interval 141 to 54 mg). However, patients who received nitrous oxide had a shorter duration of patient-controlled analgesia use (nitrous group 35 hours, no nitrous group 51 hours, mean difference -16 hours, 95% confidence interval -29 to -2 hours, P = 0.022). There was no difference in pain scores between the groups. The shorter patient-controlled analgesia duration in the nitrous oxide group suggests that intraoperative nitrous oxide may have a preventive analgesic effect.
Faiz Hossain, Chowdhury; Al-Amin, Mohammad; Rahman, Kazi Md Mahabubur; Sarker, Aurin; Alam, Md Mahamudul; Chowdhury, Mahmudul Hasan; Khan, Shamsun Nahar; Sultana, Gazi Nurun Nahar
The rhizome of Curcuma amada has been used as a folk medicine for the treatment of rheumatic disorders in the northern part of Bangladesh and has also used for the treatment of inflammation and fever in the Ayurvedic and Unani systems of medicine. Aim of the study was to investigate the analgesic principle of the MeOH extract of the rhizome of Curcuma amada by an in vivo bioassay guided chromatographic separation and purification, and the structure elucidation of the purified compound by spectroscopic methods. Dried powder of Curcuma amada rhizomes was extracted with MeOH. The analgesic activity of the crude extract and its chromatographic fractions as well as the purified compound itself was evaluated by the acetic acid induced writhing method and the formalin induced licking test in Swiss albino mice. The MeOH extract was separated by chromatographic methods and the pure active compound was purified by crystallization in hexanes. The structure of the pure compound was then elucidated by spectroscopic methods. The MeOH extract of Curcuma amada exhibited 41.63% and 45.53% inhibitions in the acetic acid induced writhing method at doses of 200mg/kg and 400mg/kg, respectively. It also exerted 20.43% and 28.50% inhibitions in early phase at doses of 200mg/kg and 400mg/kg, respectively, and 30.41% and 42.95% inhibitions in late phase at doses of 200mg/kg and 400mg/kg, respectively in the formalin induced licking test. Vacuum Liquid Chromatography (VLC) of crude extract yielded five fractions and Fr. 1 was found to have the most potent analgesic activity with inhibitions of 36.96% in the acetic acid induced writhing method and 47.51% (early phase), 39.50% (late phase) in the formalin induced licking test at a dose of 200mg/kg. Column chromatography of Fr. 1 on silica gel generated seven fractions (SF. 1-SF. 7). SF. 2 showed the most potent activity with inhibition of 49.81% in the acetic acid induced writhing method at a dose of 100mg/kg. Crystallization of SF. 2 yielded
Tyler, Matthew A; Lam, Kent; Ashoori, Faramarz; Cai, Chunyan; Kain, Joshua J; Fakhri, Samer; Citardi, Martin J; Cattano, Davide; Luong, Amber
Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results. To compare the efficacy of perioperative intravenous acetaminophen (IVAPAP) with that of placebo in improving early postoperative pain after endoscopic sinus surgery (ESS). A prospective, randomized clinical trial including 62 patients undergoing ESS for chronic rhinosinusitis in a single tertiary referral hospital. Participants were randomized to receive 1 g of IVAPAP or 100 mL of placebo consisting of saline infusions immediately before the start of surgery and 4 hours after the initial dose. The primary outcome was postoperative pain measured by visual analog scale (VAS) scores up to 24 hours after surgery by blinded observers. Secondary endpoints included postoperative opioid (intravenous and oral) use and adverse events in the 24-hour postoperative period. Of the 62 enrolled adult participants, 60 were randomized (31 to IVAPAP intervention and 29 to placebo). The mean (SD) age of participants was 53.7 (14.7) years and 35 (58%) of the participants were men and 25 (42%) were women. Within the first hour, mean pain scores were reduced in the IVAPAP group compared with the control group, reaching a maximum difference of 7.7 mm on a VAS scale favoring the treatment group with a true difference possibly as high as 22 mm, and the data are compatible with a clinically meaningful difference. At 12- and 24-hours, average pain scores were less in the placebo group and the data are compatible with a clinically meaningful difference of 5.8 (-5.2 to 16.8) and 8.2 (-1.9 to 18.4), respectively, favoring the placebo group. However, at all time points the CIs included the null value and were wide, thus preventing definitive conclusions. Inspection of the secondary outcomes favored IVAPAP, but the wide range of the CIs and inclusion of the null value prevent definitive
Full Text Available Shells are by-products of oil production from Camellia oleifera which have not been harnessed effectively. The purpose of this research is to isolate flavonoid from shells of Camellia oleifera and evaluate its anti-inflammatory and analgesic effects. The flavonoid was identified as bimolecular kaempferol structure by UV, MS, 1H NMR and 13C NMR spectra, which is a new biflavonoid and first found in Camellia oleifera. It showed dose-dependent anti-inflammatory activity by carrageenin-induced paw oedema in rats and croton oil induced ear inflammation in mice, and analgesic activity by hot plate test and acetic acid induced writhing. The mechanism of anti-inflammation of biflavonoid is related to both bradykinin and prostaglandins synthesis inhibition. The biflavonoid showed both central and peripheral analgesic effects different from aspirin, inhibition of the synthesis or action of prostaglandins may contribute to analgesic effect of biflavonoid. The biflavonoid significantly decreased malonaldehyde (MDA and increased superoxidase dismutase (SOD and Glutathione peroxidase (GSH-Px activity in serum (p < 0.01, revealed strong free radical scavenging activity in vivo. It indicates the biflavonoid can control inflammation and pain by eliminating free radical so as to inhibit the mediators and decrease the prostaglandins. The biflavonoid can be used as a prospective medicine for inflammation and pain.
The research work was aimed at investigating physiological, biochemical, analgesic and anesthetic indices of dogs anesthetized with propofol-ketamine and maintained with repeat bolus and constant infusions of propofol...
Li, Ruili; Zhao, Chao; Yao, Minna; Song, Ying; Wu, Yin; Wen, Aidong
Coumarins from Radix angelicae pubescentis (CRAP) are a major active component that are isolated from dried roots of Angelica biserrata Yuan et Shan, which has been used clinically to cure headaches for a long period of time, and it is an effective treatment for pain. The aim of the present study was to investigate the analgesic effect of CRAP on a spared nerve injury (SNI) model of neuropathy. Antinociceptive effects of CRAP were assessed in Sprague-Dawley male rats using a spared nerve injury model of neuropathic pain. Inflammatory factors were determined by Enzyme-linked immunosorbent assay (ELISA). Transient receptor potential cation channel 1 (TRPV1) and Phosphorylated extracellular regulated protein kinases (pERK) were detected by Immunofluorescence and Western blotting, respectively. The high performance liquid chromatography (HPLC) analysis showed the presence of osthole and columbianadin in Radix angelicae pubescentis. CRAP induced the dose-dependent effect of on attenuating the development of mechanical hypersensitivity. Molecular profiling revealed that CRAP reduced the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and significantly attenuated the expression of TRPV1 and pERK in damaged DRG neurons. This results demonstrate that CRAP possess remarkable antinociceptive activities which may be due to osthole and columbianadin at least in part, supporting the folkloric usage of the plant to treat various pain diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Matsumoto, Kenjiro; Horie, Syunji; Ishikawa, Hayato; Takayama, Hiromitsu; Aimi, Norio; Ponglux, Dhavadee; Watanabe, Kazuo
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.
De Santis S
Full Text Available Stefano De Santis,1 Cristina Borghesi,1 Serena Ricciardi,2 Daniele Giovannoni,1 Alberto Fulvi,2 Maria Rita Migliorino,2 Claudio Marcassa3 1Palliative Care and Cancer Pain Service, Oncological Pulmonary Unit, 2Oncological Pulmonary Unit, San Camillo-Forlanini Hospitals, Rome, 3Cardiologia Fondazione Maugeri IRCCS, Novara, Italy Introduction: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale and neuropathic pain (Douleur Neuropathique 4 were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form, Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline; 46 (82.1% patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001, Brief Pain Inventory Short Form (P=0.0002, Symptom Distress Scale (P<0.0001, Hospital Anxiety and Depression Scale depression (P=0.0006 and anxiety (P<0.0001 subscales, and bowel function (P=0.0003. At study end, 37 (66.0% patients were satisfied/very satisfied with the new analgesic treatment
Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective
Madadi, Parvaz; Enato, Ehijie F O; Fulga, Shir; Umeoduagu, Chinonye C; MacLeod, Stuart M; Koren, Gideon; Einarson, Thomas R
We conducted a systematic literature review with two objectives: (1) to assess reported patterns of analgesic use in African children and compare these observed patterns to the analgesics given in the WHO Essential Medicines List for Children (EMLc); and (2) to summarise outcomes related to effectiveness, adverse events, cost and accessibility of these analgesics. Eligible participants were children (≤12 years) living in any African country who received an analgesic administered with the intention of relieving pain in any setting. Thirty-four peer-reviewed, observational studies representing 7772 African children were accepted. Studies were conducted in 25 different regions of 12 countries. Pain was attributed to surgery, burns, sickle cell anaemia and conditions requiring palliation in 32% of children, and was unspecified in the other 68%. Of the three EMLc analgesics, paracetamol and ibuprofen were widely employed, constituting ∼60% of all analgesics, while morphine was used in 20 children (0.2%). There were 455 suspected adverse drug reactions which included 17 deaths. Analgesic use reported in African children appears to fall short of WHO standards.
Full Text Available Background. Inflammation and pain are closely related to humans’ and animals’ health. Resveratrol (RSV is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain.
Full Text Available Flupirtine (Flu, a triaminopyridine derivative, is a centrally acting, non-opiate analgesic agent. In this study, effects of Flu on K+ currents were explored in two types of motor neuron-like cells. Cell exposure to Flu decreased the amplitude of delayed rectifier K+ current (IK(DR with a concomitant raise in current inactivation in NSC-34 neuronal cells. The dissociation constant for Flu-mediated increase of IK(DR inactivation rate was about 9.8 μM. Neither linopirdine (10 μM, NMDA (30 μM, nor gabazine (10 μM reversed Flu-induced changes in IK(DR inactivation. Addition of Flu shifted the inactivation curve of IK(DR to a hyperpolarized potential. Cumulative inactivation for IK(DR was elevated in the presence of this compound. Flu increased the amplitude of M-type K+ current (IK(M and produced a leftward shift in the activation curve of IK(M. In another neuronal cells (NG108-15, Flu reduced IK(DR amplitude and enhanced the inactivation rate of IK(DR. The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K+ channels in motor neurons. Flu-induced block of IK(DR is unlinked to binding to NMDA or GABA receptors and the effects of this agent on K+ channels are not limited to its action on M-type K+ channels.
Ishola, Ismail O; Awodele, Olufunsho; Olusayero, Abayomi Micheal; Ochieng, Charles O
Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in traditional African medicine for the treatment of neuralgia, rheumatism, and arthritic pain. This study sought to investigate the analgesic and anti-inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in rodents. The analgesic activity was evaluated using the mouse writhing, formalin, and hot-plate tests while the anti-inflammatory action was investigated using the carrageenan-induced rat paw edema and xylene-induced ear edema tests. Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent (Pmuricata possesses analgesic effect through interaction with opioidergic pathway and anti-inflammatory property through inhibition of chemical mediators of inflammation.
Eissa, S I; Farrag, A M; Galeel, A A A
As a part of ongoing studies in developing new potent anti-inflammatory and analgesic agents, a series of novel 6-methoxy naphthalene derivatives was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their anti-inflammatory activities using carrageenin-induced rat paw edema model, analgesic activities using acetic acid induced writhing model in mice and anti-pyretic activity using yeast induced hyperpyrexia method as well as ulcerogenic effects. Among the synthesized compounds, thiourea derivative (6a, e) exhibited higher anti-inflammatory activity than the standard drug naproxen in reduction of the rat paw edema (88.71, 89.77%) respectively. All of the non-carboxylic tested compounds were found to have promising anti-inflammatory, analgesic and antipyretic activity, while were devoid of any ulcerogenic effects. © Georg Thieme Verlag KG Stuttgart · New York.
Mimica Matanović, Suzana
Non-opioid and opioid agents are the two main categories of analgesics. Non-opioid agents include non-steroidal anti-inflammatory drugs (NSAIDs), which further include salicylates and selective cyclooxygenase-2 inhibitors, and other non-opioid agents, e.g. acetaminophen and metamizole. Opioid agents include strong agonists, mild to moderate agonists, opioids with mixed receptor actions and miscellaneous opiods (e.g. tramadol). Other drug classes that are used as ”secondary“ analgesics are als...
Full Text Available In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25, the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A, could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC. We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.
Panhoca, Vitor Hugo; Lizarelli, Rosane de Fatima Zanirato; Nunez, Silvia Cristina; Pizzo, Renata Campi de Andrade; Grecco, Clovis; Paolillo, Fernanda Rossi; Bagnato, Vanderlei Salvador
Low-level laser therapy (LLLT) has been widely applied in pain relief in several clinical situations, including temporomandibular disorders (TMD). However, the effects of LED therapy on TMD has not been investigated. This study aims to evaluate the effects of red and infrared LEDs on: (1) tissue temperature in ex vivo and (2) pain relief and mandibular range of motion in patients with TMD. Thirty patients between 18 and 40 years old were included and randomly assigned to three groups. The two experimental groups were: the red LED (630 ± 10 nm) group and the infrared LED (850 ± 10 nm) group. The irradiation parameters were 150 mW, 300 mW/cm(2), 18 J/cm(2), and 9 J/point. The positive control group received an infrared laser (780 nm) with 70 mW, 1.7 W/cm(2), 105 J/cm(2), and 4.2 J/point. LED and laser therapies were applied bilaterally to the face for 60 s/point. Five points were irradiated: three points around the temporomandibular joint (TMJ), one point for the temporalis, and one near the masseter. Eight sessions of phototherapy were performed, twice a week for 4 weeks. Pain induced by palpating the masseter muscle and mandibular range of motion (maximum oral aperture) were measured at baseline, immediately after treatment, 7 days after treatment, and 30 days after treatment. There was an increase in tissue temperature during both the red and the infrared LED irradiation in ex vivo. There was a significant reduction of pain and increase of the maximum oral aperture for all groups (p ≥ 0.05). There was no significant difference in pain scores and maximum oral aperture between groups at baseline or any periods after treatment (p ≥ 0.05). The current study showed that red and infrared LED therapy can be useful in improving outcomes related to pain relief and orofacial function for TMD patients. We conclude that LED devices constitute an attractive alternative for LLLT.
Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg; Hansen, Lars Tambour; Kehlet, Henrik
Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized (1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache, visual disturbances, and adverse reactions. Pain upon ambulation (visual analog scale, mean [95% confidence interval]) 24 hours after surgery in group A vs B vs C was as follows: 41 [37-46] vs 41 [36-45] vs 42 [37-47], P = 0.93. Sedation (numeric rating scale, median [range]) 6 hours after surgery was as follows: 3.2 [0-10] vs 2.6 [0-9] vs 2.3 [0-9], the mean difference A vs C being 0.9 [0.2-1.7], P = 0.046. No between-group differences were observed in overall pain or morphine use the first 48 hours and from days 2-6. Sleep quality was better during the first 2 nights in group A and B vs C. Dizziness was more pronounced from days 2-6 in A vs C. More severe adverse reactions were observed in group A vs B and C. In conclusion, gabapentin may have a limited if any role in acute postoperative pain management of opioid-naive patients undergoing total knee arthroplasty and should not be recommended as a standard of care.
Full Text Available Analgesic activity of extract of papaya leaves (Carica papaya L. to male mice has been evaluated. Twenty five of mice (20-30 g, 2-3 months old were divided randomly into five groups. The first group was given sodium CMC as negative control, the second until fourth groups received ethanolic extract of Carica papaya leaves in the doses of 100, 300, and 600 mg/kgBW, respectively and the fifth group was given paracetamol 65 mg/kg BW. All interventions were administered as single dose by oral route on given day. Acetic acid 1% (w/v was used as the pain inductor. Analgesic activity was measured by counting the percentage of writhing movements as a measure of the analgesic effect produced by each intervention. Data were analyzed with one way ANOVA to compare analgesic activity between treatment groups. The results showed that the analgesic effect of the extract on the doses of 100, 300, and 600 mg/kg BW was significantly different with control group (P
Nierula, Birgit; Martini, Matteo; Matamala-Gomez, Marta; Slater, Mel; Sanchez-Vives, Maria V
Seeing one's own body has been reported to have analgesic properties. Analgesia has also been described when seeing an embodied virtual body colocated with the real one. However, there is controversy regarding whether this effect holds true when seeing an illusory-owned body part, such as during the rubber-hand illusion. A critical difference between these paradigms is the distance between the real and surrogate body part. Colocation of the real and surrogate arm is possible in an immersive virtual environment, but not during illusory ownership of a rubber arm. The present study aimed at testing whether the distance between a real and a virtual arm can explain such differences in terms of pain modulation. Using a paradigm of embodiment of a virtual body allowed us to evaluate heat pain thresholds at colocation and at a 30-cm distance between the real and the virtual arm. We observed a significantly higher heat pain threshold at colocation than at a 30-cm distance. The analgesic effects of seeing a virtual colocated arm were eliminated by increasing the distance between the real and the virtual arm, which explains why seeing an illusorily owned rubber arm does not consistently result in analgesia. These findings are relevant for the use of virtual reality in pain management. Looking at a virtual body has analgesic properties similar to looking at one's real body. We identify the importance of colocation between a real and a surrogate body for this to occur and thereby resolve a scientific controversy. This information is useful for exploiting immersive virtual reality in pain management. Copyright © 2017. Published by Elsevier Inc.
Full Text Available Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum, a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha. The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders.
Kwon, H.; Song, H.Y. [Chungnam National University, Taejon (Korea); Khang, G.S. [Chonbuk National University, Chonju (Korea); Lee, H.B. [Korea Research Institute of Chemical Technology, Taejon (Korea)
The fundamental properties of transdermal therapeutic patch as narcotic analgesics agent has been investigated. From the study of drug and ethanol release patterns from the fentanyl base (FB) patches through diffusion cell and hairless mouse skin, it was observed that the FB release patterns were largely affected by the content of vinyl acetate (VA) of ethylene-co-vinyl acetate (EVA) membrane, and volume fraction of ethanolic solution. Additionally, a variety of control membrane as a function of VA content were examined for swelling following equilibration with ethanolic solutions. Generally, ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. In vitro skin permeation analysis of the control membrane showed that ethanol flux was linearly related to the ethanol volume fraction. This result was shown that drug permeability increased with increasing as the content of VA. But, the FB flux from saturated aqueous ethanol solutions increases until 80% ethanol volume fraction. Over 80% ethanol volume fraction, the FB flux through skin samples is independent of ethanol volume. These results showed that the decrease in skin permeation due to dehydration nis the dominant effect. 26 refs., 8 figs.
Full Text Available Introduction: A way to assess compliance with analgesics in an outpatient palliative care clinic is essential since often the patient is too ill or weak to come to hospital for weekly follow-ups. A pilot study was conducted using Short Messaging Service via mobile phone as a follow-up tool. Context: A predominantly outpatient palliative care clinic of a 300 bedded multidisciplinary hospital. Materials and Methods: Sixty patients attending the palliative care clinic were enrolled in the study. Analgesic drugs, co-analgesics, and adjuvants were prescribed on an outpatient basis. If possible, patients were admitted for 1 or 2 days. A simple scoring system was devised and taught to the patients and their attenders. A short message service had to be sent to the author′s mobile number. The period was fixed at 2 weeks by which the patients and attenders were familiar with the drugs and pain relief as well. Drowsiness was a worrisome complaint. The mobile number of the patient was called and attender instructed to skip one or two doses of morphine and reassurance given. If required, attender was asked to bring patient to the hospital or come to the hospital for a different prescription as the situation warranted. Results: Out of 60 patients, 22 were admitted initially for dose titration and all others were outpatients. Three patients were lost to follow-up and one patient died after 7 days. 93% of patients responded promptly. Random survey was done in 10 patients to confirm their SMS response and the results were analyzed. Conclusion: Mobile phones are available with all strata of people. It is easy to train patients to send an SMS.This technology can be used to follow- up palliative care patients and help them comply with their treatment regimen.
dos Santos, Gilson Gonçalves; Dias, Elayne Vieira; Teixeira, Juliana Maia; Athie, Maria Carolina Pedro; Bonet, Ivan José Magayewski; Tambeli, Cláudia Herrera; Parada, Carlos Amilcar
Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation in the anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50µL/paw) was locally administered in the hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von Frey test, before and 3h after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression was intrathecally administered once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti-hyperalgesic effect by cGMP activation and KATP opening. Copyright © 2014 Elsevier B.V. All rights reserved.
Ravn, Pernille; Foster, David J. R.; Kreilgaard, Mads
scaling for weight provided the best description of the plasma concentration-time profile of morphine. Changes in the EPTo and 2HA responses with time during the placebo treatment were best described by a linear model and a quadratic model, respectively. The model discrimination process showed clear...... pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo....
Full Text Available This work has been done for the investigation of the anti-inflammatory and analgesic activity of methanol extract of dried leaves of Murraya koenigii Linn by oral administration at dose of 100, 200 and 400 mg/kg body weight, to healthy animals. Extract was studied for its anti-inflammatory activity by using carrageenan-induced hind paw edema in albino rats and the mean increase in paw volume and % inhibition in paw volume were measured plethysmometrically at different time intervals after carrageenan (1% w/v injection. Extract was also evaluated for analgesic activity using Eddy′s hot plate method and formalin induced paw licking method in albino rats. The methanol extract showed significant (P < 0.001 reduction in the carrageenan-induced paw edema and analgesic activity evidenced by increase in the reaction time by eddy′s hot plate method and percentage increase in pain in formalin test. The methanol extract showed anti-inflammatory and analgesic effect in dose dependent manner when compared with the control and standard drug, diclofenac sodium (10mg/kg, p.o. These inhibitions were statistically significant (P < 0.05. Thus our investigation suggests a potential benefit of Murraya koenigii in treating conditions associated with inflammatory pain.
Morales-Muñoz, C; Sánchez-Ramos, J L; Díaz-Lara, M D; González-González, J; Gallego-Alonso, I; Hernández-Del-Castillo, M S
Total knee replacement is usually a very painful procedure. A single-dose of femoral nerve block has been shown to provide similar analgesia to an epidural, with fewer side effects, but limited in time. To compare the analgesia provided by dexamethasone used at perineural level in the femoral nerve block after total knee replacement with the one used at intravenous level, and with that of a control group. A prospective, randomised, double-blind controlled trial was conducted on 81 patients randomly assigned to one of three groups: 1)IV dexamethasone (8mg); 2)perineural dexamethasone (8mg), and 3)placebo. All patients received 20ml of ropivacaine 0.5% for femoral nerve block. The primary outcome was the duration of the sensory-analgesic block of the femoral nerve block. The secondary outcomes included pain intensity measurements, patient satisfaction, and incidence of complications. Randomisation was effective. Analgesia duration was significantly higher (P<.0001) in the perineural dexamethasone group (mean 1152.2min, 95% confidence interval [95% CI]: 756.9-1547.6) in comparison with the control group (mean 186min, 95%CI: 81.2-292) and dexamethasone IV group (mean 159.4min, 95%CI: 109.8-209). Postoperative pain, complications and side effects were also lower in this group. Dexamethasone prolongs sensory block of single dose of femoral nerve block using ropivacaine. It also provides better analgesia and patient satisfaction, with fewer side effects. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N or naproxen sodium-codeine phosphate (Group NC before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS. Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p 0.05. CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.
Full Text Available Background and objectives: Esmolol is known to have no analgesic activity and no anaesthetic properties; however, it could potentiate the reduction in anaesthetic requirements and reduce postoperative analgesic use. The objective of this study is to evaluate the effect of intravenous esmolol infusion on intraoperative and postoperative analgesic consumptions as well as its effect on depth of anaesthesia. Methods: This randomized-controlled double blind study was conducted in a tertiary care hospital between March and June 2010. Sixty patients undergoing septorhinoplasty were randomized into two groups. History of allergy to drugs used in the study, ischaemic heart disease, heart block, bronchial asthma, hepatic or renal dysfunction, obesity and a history of chronic use of analgesic or β-blockers were considered cause for exclusion from the study. Thirty patients received esmolol and remifentanil (esmolol group and 30 patients received normal saline and remifentanil (control group as an intravenous infusion during the procedure. Mean arterial pressure, heart rate, and bispectral index values were recorded every 10min. Total remifentanil consumption, visual analogue scale scores, time to first analgesia and total postoperative morphine consumption were recorded. Results: The total remifentanil consumption, visual analogue scale scores at 0, 20 and 60 min, total morphine consumption, time to first analgesia and the number of patients who needed an intravenous morphine were lower in the esmolol group. Conclusions: Intravenous infusion of esmolol reduced the intraoperative and postoperative analgesic consumption, reduced visual analogue scale scores in the early postoperative period and prolonged the time to first analgesia; however it did not influence the depth of anaesthesia.
Sarkar, Chayna; Das, Biswadeep; Baral, P
with opioid analgesics only. No gastroprotective was used when NSAIDs were prescribed alone or in combination with paracetamol. Our present study indicate that all the analgesics were prescribed in oral dosage forms but analgesics prescribed in generic name (5%) and from essential drug lists (37.8%) were very less. There was an inclination to prescribe the older non-opioid analgesics. Selection of analgesics was quite rational in our study but some lacunae were observed. A total of 38.9% analgesics were FDCs and most common FDC analgesics were ibuprofen + paracetamol. Avoiding unnecessary FDCs may help in reducing prescribing costs because FDCs usually cost more than single ingredient preparations. It is best to avoid combination therapy with more than one non-opioid analgesic; there is little evidence of extra benefit to the patient and the incidence of side effects generally is additive. Prescribing generic names aids in avoiding confusion and minimizing the costs. In the present study, coprescription of gastroprotective agents with analgesic use was low compared to a previous study but when opioid analgesics were prescribed, concurrent use of gastroprotective agents were irrational as opioid analgesics usually decrease the secretion of hydrochloric acid. It is also surprizing that, no gastroprotective was used when NSAIDs were prescribed alone, irrespective of sex, age, dose or duration or type of NSAID treatment in our study. There is a clear need for the development of prescribing guidelines and educational initiatives to encourage the rational and appropriate use of analgesics in dentistry. 2004 John Wiley & Sons, Ltd.
Logashina, Yulia A; Mosharova, Irina V; Korolkova, Yulia V; Shelukhina, Irina V; Dyachenko, Igor A; Palikov, Victor A; Palikova, Yulia A; Murashev, Arkadii N; Kozlov, Sergey A; Stensvåg, Klara; Andreev, Yaroslav A
The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino acid peptide cross-linked by two disulfide bridges named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as a therapeutic approach as Ms 9a-1 produces significant analgesic and anti-inflammatory effects in mice models of pain. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Saraghi, Mana; Hersh, Elliot V.
Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain. PMID:24423420
Rezaee-Asl, Masoume; Sabour, Mandana; Nikoui, Vahid; Ostadhadi, Sattar; Bakhtiarian, Azam
Leonurus cardiaca, commonly known as motherwort, is a member of the Lamiaceae family. It has a number of interesting biological activities, for example, sedative and hypotensive, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of the present study was to investigate the effect of alcoholic extract of aerial part of Leonurus cardiaca on nociceptive response using formalin, tail flick, and hot plate tests in mice. The acute treatment of mice with an ethanolic extract at doses of 500 and 250 mg/kg by intraperitoneal administration produced a significant antinociceptive in the first and second phases of formalin test, respectively. The hot plate and tail flick tests showed an increase in the antinociceptive effect at dose 500 mg/kg. These results suggest that Leonurus cardiaca possesses central and peripheral antinociceptive actions.
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.
Zeb, Anwar; Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul
Isodon rugosus Wall. ex Benth. is extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache, and generalized body pain. The current study is designed to scientifically verify the purported uses of I. rugosus as analgesic agent and to figure out its possible mechanism of action. Bioactive compounds responsible for analgesic activity were identified using GC and GC-MS analysis. Analgesic potentials were evaluated using acetic acid induced writhing, hot plate test, and formalin induced paw licking test. In acetic acid induced writhing chloroform fraction (Ir.Chf) exhibited 53% analgesia while formalin test displayed 61% inhibition at phase-I and 45% at phase-II respectively at a dose of 100 mg/kg. Similarly, in hot plate test Ir.Chf displayed average reaction time of 7 min at 15, 30, 45, and 60 min intervals. The possible mechanism of action was found to be the central pathway via opioidergic receptors as the mice showed morphine like analgesic activity at pre-administration of naloxone (opioid antagonist) in hot plate and formalin tests. In GC-MS analysis, 83 compounds were identified among which eight compounds including benzyl alcohol, sebacic acid, myristic acid, phytol, sugiol, Tocopherol, α-Amyrin, and stigmasterol were sorted out as previously reported analgesic compounds. Current study revealed that analgesic potential of I. rugosus can attributed to the presence of analgesic compounds. It may also be concluded that opioids receptors are involved in the analgesic mechanism of I. rugosus due to effective antagonism of nalaxone.
Beena K Parikh
Full Text Available Background: Transversus abdominis plane (TAP block is suitable for lower abdominal surgeries. Blind TAP block has many complications and uncertainty of its effects. Use of ultrasonography increases the safety and efficacy. This study was conducted to evaluate the analgesic efficacy of ultrasound (USG-guided TAP block for retroperitoneoscopic donor nephrectomy (RDN. Methods: In a prospective randomized double-blind study, 60 patients undergoing laparoscopic donor nephrectomy were randomly divided into two groups by closed envelope method. At the end of surgery, USG-guided TAP block was given to the patients of both the groups. Study group (group S received inj. Bupivacaine (0.375%, whereas control group (group C received normal saline. Inj. Tramadol (1 mg/kg was given as rescue analgesic at visual analog scale (VAS more than 3 in any group at rest or on movement. The analgesic efficacy was judged by VAS both at rest and on movement, time to first dose of rescue analgesic, cumulative dose of tramadol, sedation score, and nausea score, which were also noted at 30 min, 2, 4, 6, 12, 18, and 24 h postoperatively. Total tramadol consumption at 24 h was also assessed. Results: Patients in group S had significantly lower VAS score, longer time to first dose of rescue analgesic (547.13±266.96 min vs. 49.17±24.95 min and lower tramadol consumption (103.8±32.18 mg vs. 235.8±47.5 mg in 24 h. Conclusion: The USG-guided TAP block is easy to perform and effective as a postoperative analgesic regimen in RDN, with opioids-sparing effect and without any complications.
Saeed, Shaam; Bshara, Nada; Trak, Juliana; Mahmoud, Ghiath
Objectives: To study the effect of water, halloumi cheese and sugar-free (SF) chewing gum on plaque pH recovery after the intake of sweetened PLAs. Settings and Design: A randomized clinical trial was conducted on 17 children (10 females, 7 males) aged 11–12 years with DFT/dft of more than 3. Materials and Methods: Each volunteer tested paracetamol and ibuprofen suspension alone or followed with water, halloumi cheese or SF gum, as well as 10% sucrose and 10% sorbitol as controls. Plaque pH w...
Linnoila, M.; Seppälä, T.; Mattila, M. J.
1 The effect of acetylsalicylic acid (1 g), indomethacin (50 mg), and phenylbutazone (200 mg) on psychomotor skills was examined double blind on 180 volunteer students. Ninety students received ethyl alcohol (0.5 g/kg) and 90 subjects an equal volume of placebo drink in combination with the drugs. 2 Psychomotor skills were measured with a choice reaction test, two co-ordination tests, and a divided attention test, having correlation with traffic behaviour. The subjects assessed their feelings of performance by means of a rating scale. The tests were done 30, 90 and 150 min after the administration of the agents. 3 Acetylsalicylic acid proved inactive whereas both indomethacin and phenylbutazone impaired eye-hand co-ordination and divided attention. Acetylsalicylic acid did not interact with alcohol to a measurable extent whereas indomethacin in combination with alcohol proved less harmful than without it. The deleterious effects of phenylbutazone and alcohol were additive. 4 An impairment of psychomotor skills related to driving by indomethacin and phenylbutazone should be considered when prescribing these drugs to active out-patients. PMID:22454933
Opioid analgesics exhibit cationic properties under physiological conditions, and the mechanism underlying permeation of the blood-brain barrier thus cannot be fully explained by simple diffusion alone. Various types of transporters that exhibit substrate specificity are localized on the blood-brain barrier, and play a role in transporting substances from circulating blood and from brain interstitial fluid. Progress is being made in explaining the mechanisms, functions, and physiological roles of polyspecific organic cation transporters, but little evidence has indicated that these previously identified organic cation transporters are involved in the transport of opioid analgesics across the blood-brain barrier. Consequently, clarifying the role of transporters in the distribution of opioid analgesics into the brain and determining their transport molecule will not only provide clues to effective drug delivery to the brain, but will also contribute to optimizing pain relief treatment, and by extension play a role in drug discovery for analgesics. Currently there are enthusiastic discussions in the literature regarding the existence of putative transporters involved in the transport of opioid analgesics across the blood-brain barrier. This review article introduces the results of our research as well as recent findings on the involvement of transporters in the blood-brain barrier transport of opioid analgesics such as morphine, morphine metabolites, oxycodone, fentanyl, codeine, and pentazocine.
Venkatesh, Sama; Fatima, Saba
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
inflammatory and analgesic activities in rats. The effects of the extract on acute inflammation were studied in carrageenan and dextran-induced paw oedema in rats. Analgesic effect of the extract was evaluated using acetic acid induced writhing and ...
Martini, C H; Proto, P; Olofsen, E; van Velzen, M; Aarts, L; Dahan, A; Niesters, M
For effective treatment of acute pain, a rapid onset of action is important. Here we quantify the antinociceptive profile of an orodispersible oxycodone tablet (OOT) in a randomized, double-blind, active comparator (paracetamol orodispersible tablet, POT), crossover study design in a population of healthy volunteers. Twelve female volunteers were randomized to receive 20 mg OOT and 500 mg POT sublingually on two occasions. The electrical pain threshold (EPTh), electrical pain tolerance (EPTol) and pressure pain threshold (PPT) were obtained at regular intervals for 5 h. Time-response data were analysed with a longitudinal pharmacodynamic model characterized by rate constants for analgesia onset (kON ), offset (kOFF ), potency parameter (EFF) and validated with a bootstrap analysis. Values are the median (95% CI) as derived from the bootstrap analysis. OOT produced a rapid increase in response values. For electrical pain analgesia onset, t½kON , 44 (25-67) versus analgesia offset, t½kOFF , 156 (63-552) min, p mathematical model of analgesia evolution. This method allows quantification of a variety of responses times from sparse data sets. Response times as defined by a 30% increase in response thresholds varied significantly among end points: EPTol 15 min, PPTh 18 min and EPTh 41 min. © 2014 European Pain Federation - EFIC®
Full Text Available The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.
Shah, Lipa; Kulkarni, Praveen; Ferris, Craig; Amiji, Mansoor M
The main objective of this study was to develop and evaluate therapeutic efficacy and safety following systemic delivery of a peptide analgesic into the CNS using an oil-in-water nanoemulsion system. We have formulated a safe and effective, omega-3 rich polyunsaturated fatty acid containing oil-in-water nanoemulsion formulation, for encapsulating and delivering chemically-modified DALDA, a potent mu-opioid peptide analogue, to the CNS. One of the challenges with CNS delivery is the lack of a non-invasive bioanalytical technique to confirm CNS uptake and therapeutic efficacy. Using blood oxygen-level dependent (BOLD) functional magenetic resonance imaging (fMRI), we provide quantitative evidence of nanoemulsion-based delivery and analgesic activity of DALDA analogue in capsaicin-induced awake rat model of pain. Nanoemulsion formulation effectively encapsulated the modified analgesic peptide and demonstrated efficacy in the capsaicin- pain induced functional magnetic resonance imaging model in rodents. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects. Overall, these results show tremendous opportunity for the development of modified peptide analgesic-encapsulated nanoemulsion formulations for CNS delivery and therapeutic efficacy.
Quiding, Hans; Jonzon, Bror; Svensson, Ola; Webster, Lynn; Reimfelt, Annika; Karin, Aleksandra; Karlsten, Rolf; Segerdahl, Märta
The effects of a TRPV1 antagonist (AZD1386) were investigated in patients with acute pain. After removal of a mandibular third molar and at request of analgesia 103 patients randomly received 95 mg AZD1386 (n = 40), placebo (n = 40) or 500 mg naproxen (n = 23) in a double-blind manner. Plasma samples were drawn, and pain intensity and body temperature were measured during 8 h after drug administration. The pain intensity difference from drug intake was calculated as a percentage (PID%) and as a weighted sum over the 8 h (SPID%0-8 h). The time to first perceptible and first meaningful pain relief was recorded. SPID%(0-8) h showed no significant difference between AZD1386 and placebo (P = .132) but between naproxen and placebo (P = .038). AZD1386 had a rapid short-lasting analgesia and compared to placebo, PID% was significantly higher (P ≤ .026) at 0.25, 0.50, 0.75 and 1.00 h after drug administration. Correspondingly, for naproxen significantly higher PID% (P ≤ .021) was seen at 2.5, 3, 4, 5, 6, 7 and 8 h. The frequency of patients obtaining perceptible and meaningful pain relief was about 85% and 48% after AZD1386 and about 53% and 25% after placebo. The occurrence of perceptible and meaningful pain relief was significantly faster (P = .002 and P = .031) for AZD1386 compared to placebo. Adverse events were similar to placebo with the exception of 2 patients reporting chills. The highest individual body temperature after AZD1386 was 38.1°C, recorded in 2 patients. In summary, AZD1386 was well tolerated with a rapid analgesia that was short lasting despite sustained plasma concentration. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
--Codeine phosphate is the most commonly used analgesic post-craniotomy. --It is argued, in this paper, that codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy. --Lack of evidence supporting tramadol's usage and concerns over its interactions and side effects mean its use cannot be advocated. --The traditional justification for withholding morphine in post-craniotomy pain appears to be largely based on anecdotal evidence. --Raising awareness among critical care nurses of the pharmacological properties of the analgesics used is imperative, if post-craniotomy pain is to be adequately treated. --There is an explicit challenge to the neurosurgical community to re-evaluate their pain-management strategies in the post-craniotomy patient.
Full Text Available Objective(sCurrent study was undertaken to investigate the analgesic and anti-inflammatory effects of the aqueous extract of Teucrium chamaedrys in mice and rats. Materials and MethodsFor evaluating of analgesic and anti-inflammatory activity, we used the carrageenan- and dextran-induced paw oedema, acetic acid-induced writhing, tail flick and formalin pain tests.ResultsThe extract of T. chamaedrys (50–200 mg/kg and acetylsalicylic acid (100 mg/kg produced a significant (P< 0.01 inhibition of the second phase response in the formalin pain model, while only the high dose (200 mg/kg of the extract showed an analgesic effect in the first phase. The extract also inhibited acetic acid-induced abdominal writhes in a dose-dependent manner. The tail flick latency was dose dependently enhanced by the extract but this was significantly (P< 0.05 lower than that produced by morphine (10 mg/kg. The extract (25–250 mg/kg administered 1 hr before carrageenan-induced paw swelling produced a dose dependent inhibition of the oedema. No effect was observed with the dextran-induced oedema model. Results of the phytochemical screening show the presence of alkaloids, flavonoids and triterpenoids in the extract.ConclusionThe data obtained also suggest that the anti-inflammatory and analgesic effects of the extract may be mediated via both peripheral and central mechanisms. The role of alkaloids, flavonoids and triterpenoids will evaluate in future studies.
Analgesic effect of cathodal transcranial current stimulation over right dorsolateral prefrontal cortex in subjects with muscular temporomandibular disorders: study protocol for a randomized controlled trial.
Brandão Filho, Rivail Almeida; Baptista, Abrahão Fontes; Brandão, Renata de Assis Fonseca Santos; Meneses, Francisco Monteiro; Okeson, Jeffrey; de Sena, Eduardo Pondé
Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain. The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score. Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular
nervous system drugs. A high percentage (82.2%) of the analgesic agents dispensed were combination or polycomponent analgesics. The combination analgesic tablet, consisting of paracetamol, meprobamate, caffeine and codeine phosphate, was the most frequently prescribed central nervous system drug. This product.
Tasleem, Farhana; Azhar, Iqbal; Ali, Syed Nawazish; Perveen, Shaista; Mahmood, Zafar Alam
To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (PPiper nigrum L possesses potent analgesic and anti-inflammatory activities. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Conclusion: Single preemptive oral dose of tapentadol (75 mg is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects.
Shalaby, Mostafa Abbas; Hammouda, Ashraf Abd-Elkhalik
The aim was to evaluate the analgesic, anti-inflammatory, and anti-hyperlipidemic activities of Commiphora molmol extract (CME) and its effects on body weight and blood lipids. The analgesic effect was assessed using thermal (hot plate test) and chemical (writhing test) stimuli to induce central and peripheral pain in mice. The anti-inflammatory activity was determined using formalin-induced paw edema in rats. For anti-hyperlipidemic effect, 25 rats were randomly divided into five groups (n = 5). Group 1 was fed on basal diet (normal control), while the other four groups were fed on high-fat diet for 6 weeks to induce obesity and hyperlipidemia. Thereafter, Group 2 was kept obese hyperlipidemic, and Groups 3, 4 and 5 were orally given CME in doses of 125, 250, and 500 mg/kg for 6 weeks, respectively. Body weight gains of rats were calculated, and blood samples were collected for analysis of blood lipids. CME produced a dose-dependent analgesic effect using both hot plate and writhing tests in mice. The hot plate method appeared to be more sensitive than writhing test. CME exhibited an anti-inflammatory activity as it decreased volume of paw edema induced by formalin in rats. The extract decreased body weight gain; normalized the high levels of blood lipids and decreased atherogenic index low-density lipoprotein/ high-density lipoprotein in obese hyperlipidemic rats. The results denote that C. molmol extract (myrrh) has significant analgesic, anti-inflammatory and anti-hyperlipidemic effects and reduces body weight gain and improves blood lipids profile. These results affirm the traditional use of C. molmol for the treatment of pain, inflammations, and hyperlipidemia.
Mostafa Abbas Shalaby
Full Text Available Aim: To evaluate the analgesic, anti-inflammatory and antihyperlipidemic activities of Commiphora molmol extract (CME and its effect on body weight. Material and Methods: The analgesic effect was assessed using thermal (hot plate test and chemical (writhing test stimuli to induce central and peripheral pain in mice. The anti-inflammatory activity was determined using formalin-induced paw edema in rats. For antihyperlipidemic effect, thirty five rats were randomized into five equal groups (n=7. Group (1 was fed on basal diet (Normal control, while the other 4 groups were fed on high-fat diet for 6 weeks to induce obesity and hyperlipidemia. Thereafter, group (2 was kept obese hyperlipidemic, and groups (3, (4 and (5 were orally given CME in doses of 125, 250 and 500 mg/kg for 6 weeks, respectively. Body weight gains of rats were calculated and blood samples were collected for analysis of blood lipids. Results: CME produced a dose-dependent analgesic effect using both hot plate and writhing tests in mice. The hot plate method appeared to be more sensitive than writhing test. CME exhibited an anti-inflammatory activity as it reduced volume of paw edema induced by formalin in rats. This extract decreased body weight gains; normalized the high levels of blood lipids and decreased atherogenic index (LDL/HDL in obese hyperlipidemic rats. Conclusion: The results of this study denote that Commiphora molmol extract (Myrrh has significant analgesic, anti-inflammatory, and antihyperlipidemic effects and decreases body weight. These results affirm the traditional use of Commiphora molmol for the treatment of pain, inflammations, and hyperlipidemia. [J Intercult Ethnopharmacol 2014; 3(2.000: 56-62
Thereza C. M. de Lima; Gina S. Morato; Reinaldo N. Takahashi
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...