Evaluation of Anti-Hyperalgesic and Analgesic Effects of Two Benzodiazepines in Human Experimental Pain: A Randomized Placebo-Controlled Study

Background The analgesic activity of morphine-6-glucuronide (M-6-G) is well recognized for its contribution to the effects of morphine and its possible use as an opioid analgesic with a wider therapeutic range than morphine. The present study attempted to quantify the relative contribution of M-6-G to analgesia observed after systemic administration of morphine. Methods In a placebo-controlled, sixfold crossover study in 20 healthy men, the effects of M-6-G were assessed at steady-state plasma concentrations of M-6-G identical to and two and three times higher than those measured after administration of morphine. Morphine and M-6-G were administered as an intravenous bolus followed by infusion over 4 h. Dosage A was M-6-G-bolus of 0.015 mg/kg plus infusion of 0.0072 mg x kg(-1) x h(-1). Dosage B was M-6-G-bolus of 0.029 mg/kg plus infusion of 0.014 mg x kg(-1) x h(-1). Dosage C was M-6-G-bolus of 0.044 mg/kg plus infusion of 0.022 mg x kg(-1) x h(-1). Dosage D was a morphine bolus of 0.14 mg/kg plus infusion of 0.05 mg x kg(-1) x h(-1) for 4 h. Dosage E was M-6-G combined with morphine (doses A + D). Dosage F was a placebo. The analgesic effects of M-6-G and morphine were measured before administration of the bolus and after 3.5 h using an experimental pain model based on pain-related cortical potentials and pain ratings after specific stimulation of the nasal nociceptor with short pulses of gaseous carbon dioxide. Results Morphine significantly reduced subjective and objective pain correlates compared with placebo. In contrast, M-6-G produced no statistically significant effects. The addition of M-6-G to morphine did not increase the effects of morphine. Morphine produced significantly more side effects than M-6-G. Conclusion After short-term intravenous administration at doses that produce plasma concentrations of M-6-G similar to those seen after administration of morphine, M-6-G had no analgesic effects in the present placebo-controlled study in healthy volunteers.

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OPRM1, OPRK1, and COMT genetic polymorphisms associated with opioid effects on experimental pain: a randomized, double-blind, placebo-controlled study

The Pharmacogenomics Journal ◽

10.1038/s41397-019-0131-z ◽

2019 ◽

Vol 20 (3) ◽

pp. 471-481 ◽

Cited By ~ 2

Author(s):

Kwo Wei David Ho ◽

Margaret R. Wallace ◽

Roland Staud ◽

Roger B. Fillingim

Keyword(s):

Genetic Polymorphisms ◽

Experimental Pain ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.83577 ◽

2011 ◽

Vol 02 (02) ◽

pp. 130-136 ◽

Cited By ~ 9

Author(s):

Keshab Raj Paudel ◽

SK Bhattacharya ◽

GP Rauniar ◽

BP Das

Keyword(s):

Pain Perception ◽

Late Phase ◽

Antinociceptive Effect ◽

Experimental Pain ◽

Mechanical Hyperalgesia ◽

Tail Flick ◽

Hot Plate ◽

Analgesic Effects ◽

Pain Models ◽

Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

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Analgesic effect of methanolic extract obtained from Schinus terebinthifolius leaves

Journal Biomedical and Biopharmaceutical Research ◽

10.19277/bbr.17.2.234 ◽

2020 ◽

Vol 17 (2) ◽

pp. 1-12

Author(s):

Pedro Cruz de Oliveira Jr. ◽

Eloise Balen ◽

Jucicleia da Silva Arrigo ◽

Anelise Samara Nazari Formagio ◽

Marciane Maximo da Silva ◽

...

Keyword(s):

Locomotor Activity ◽

Methanolic Extract ◽

Forced Swim Test ◽

Experimental Pain ◽

Mechanical Hyperalgesia ◽

Heat Sensitivity ◽

Schinus Terebinthifolius ◽

Analgesic Effects ◽

Swiss Mice ◽

Analgesic Agents

Previous studies from our group showed the analgesic effects of essential oil and extracts of Schinus terebinthifolius. The aims of this research were to evaluate the anti-nociceptive, anti-arthritic properties of methanolic extract obtained from S. terebinthifolius (MEST) leaves in animal models of experimental pain and arthritis. The MEST (30 and 100 mg/kg) reduced both phases of formalin induced licking behavior in Swiss mice. The MEST (100 mg/kg) reduced mechanical hyperalgesia induced by carrageenan in swiss mice. The MEST (100 mg/kg) oral administration reduced significantly the mechanical hyperalgesia (day 2, 5, 10, and 20), knee oedema (day 2), cold (day 15) and heat sensitivity (day 20), but not depressive-like behavior (Forced Swim Test), after Complete Freund's Adjuvant (CFA) in C57B16 mice. The MEST prevented the anti-nociceptive effects in formalin nociception and did not interfere with locomotor activity in Swiss mice (open field test). The MEST was effective for the inhibition of pain and arthritic parameters without altering locomotor activity or depressive-like behavior. The present results may open new possibilities for the development of new analgesic agents from S. terebinthifolius.

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Analgesic Effects of Thiamine in Male Long Evans Rats

Journal of Bangladesh Society of Physiologist ◽

10.3329/jbsp.v12i1.33921 ◽

2017 ◽

Vol 12 (1) ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Sayema Ainan ◽

Noorzahan Begum ◽

Taskina Ali

Keyword(s):

Experimental Pain ◽

Immersion Test ◽

Writhing Test ◽

Analgesic Effects ◽

Inhibitory Mechanisms ◽

Significant Decrement ◽

Pain Models ◽

Tail Immersion ◽

Long Evans ◽

Post Hoc

Background: The concept of analgesic effects of thiamine along with other B vitamins has been supported since long by various clinical and experimental evidences, though effects of individual thiamine on pain are yet to be clearly demonstrated.Objective: To assess the effects of increasing doses of thiamine supplementation on pain.Methods: Forty-eight (48) male Long Evans rats (200±20 gm) were given thiamine (100, 200, 250, mg/kg/day; experimental) or normal saline (5 ml/kg/day; control) intraperitonealy (i.p) for 7 consecutive days. The analgesic activity was evaluated by three experimental pain models, hot (52±0.50C) water tail immersion test, the interphase (6th-15th minutes) of formalin (50?l, 2.5%, subcutaneous) test and acetic acid (2%, i.p) induced writhing test. Statistical analysis was done by ANOVA followed by Bonferroni post hoc test and p?0.05 was considered as significant.Results: In tail immersion test, %MPE significantly increased after 200 (p?0.05) and 250 (p?0.001) mg/kg of thiamine. In the formalin test, thiamine significantly lowered the jerking frequency (p?0.05, p?0.001, p?0.001, respectively) and duration of flexing and licking (p?0.001, in all doses), compared to control. In addition, in writhing test, significant increment in latency of appearance of 1st writhe (p?0.001, in higher 2 doses) and significant decrement in frequency of writhes (p?0.01, p?0.001, p?0.001, respectively, in all doses) were observed.Conclusion: The results of this study conclude that, repetitive administration of thiamine may cause alleviation of pain through central as well as peripheral inhibitory mechanisms, which is dose dependent as well.Bangladesh Soc Physiol. 2017, June; 12(1): 1-9

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Influence of Naloxone and Methysergide on the Analgesic Effects of Low-Level Laser in an Experimental Pain Model

Brazilian Journal of Anesthesiology ◽

10.1016/s0034-7094(10)70037-4 ◽

2010 ◽

Vol 60 (3) ◽

pp. 302-310 ◽

Cited By ~ 9

Author(s):

André Peres e Serra ◽

Hazem A. Ashmawi

Keyword(s):

Experimental Pain ◽

Pain Model ◽

Low Level ◽

Analgesic Effects ◽

Low Level Laser ◽

Level Laser

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The analgesic effects of interferential therapy on two experimental pain models: cold and mechanically induced pain

Physiotherapy ◽

10.1016/j.physio.2005.09.007 ◽

2006 ◽

Vol 92 (2) ◽

pp. 95-102 ◽

Cited By ~ 18

Author(s):

Fiona J. McManus ◽

Alex R. Ward ◽

Val J. Robertson

Keyword(s):

Experimental Pain ◽

Analgesic Effects ◽

Pain Models ◽

Interferential Therapy

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Comparative Study of 0.2% Glyceryl Trinitrate Ointment for Pain Reduction after Hemorrhoidectomy Surgery

The Surgery Journal ◽

10.1055/s-0039-3400532 ◽

2019 ◽

Vol 05 (04) ◽

pp. e192-e196 ◽

Cited By ~ 1

Author(s):

Sepideh Vahabi ◽

Siavash Beiranvand ◽

Arash Karimi ◽

Mahmoudreza Moradkhani

Keyword(s):

Glyceryl Trinitrate ◽

Controlled Study ◽

Analog Scale ◽

Double Blind ◽

Mean Values ◽

Analgesic Effects ◽

Total Pain ◽

Significant Difference ◽

The Mean ◽

Glyceryl Trinitrate Ointment

Abstract Context Hemorrhoid is one of the most common diseases in both, men and women, affecting half of the world's population over the age of 50. Aims The aim of this study was to evaluate the analgesic effects of local ointment of glyceryl trinitrate ointment (GTN) after hemorrhoidectomy. Methods and Materials In this randomized double-blind, placebo-controlled study, the patients were grouped as the treatment, that is GTN, and placebo (P) group. After surgery, 0.2% gelatin GTN ointment (250 mg), and P ointment (n = 20 for each group) were applied topically on 1 cm on the anus using a standard ruler, three times a week in respective groups. visual analog scale was used to assess the intensity of the pain and complications of the drugs were observed at 6, 12, 18, and 24 hours. Statistical Analysis Used Data and questionnaires were analyzed statistically using SPSS17 software and results were recorded in the tabular form. Results Six hours after the application of the ointment, no significant difference was found among the groups, however, after 12, 18, and 24 hours significant reduction in pain was seen in GTN group, which was least after 18 hours. The mean values of the total pain score in the first 24 hours after surgery in the GTN group were 3.15 and 5.45 in the P group which were statistically significant. Nonetheless, headache was significantly increased in the GTN group. Conclusion Simple and safe topical GTN ointment can reduce the pain after hemorrhoidectomy, leading to the reduced need of other analgesics.

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