Experimental Pain Models Reveal No Sex Differences in Pentazocine Analgesia in Humans

2004 ◽  
Vol 100 (5) ◽  
pp. 1263-1270 ◽  
Author(s):  
Roger B. Fillingim ◽  
Timothy J. Ness ◽  
Toni L. Glover ◽  
Claudia M. Campbell ◽  
Donald D. Price ◽  
...  
Keyword(s):  
Sex Differences ◽  
Oral Surgery ◽  
Experimental Pain ◽  
Double Blind ◽  
Analgesic Effects ◽  
Kappa Agonist ◽  
Pain Models ◽  
Before And After ◽  
Highly Correlated ◽  
Pain Stimuli

Background Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. Methods Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. Results Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. Conclusions These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.

scholarly journals 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

2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
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.

scholarly journals Analgesic Effects of Thiamine in Male Long Evans Rats

2017 ◽  
Vol 12 (1) ◽  
pp. 1-9 ◽  
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

On the pharmacological effects of two lidocaine concentrations tested on spontaneous and evoked pain in human painful neuroma: A new clinical model of neuropathic pain

2013 ◽  
Vol 4 (4) ◽  
pp. 258
Author(s):  
Adriana Miclescu ◽  
Björn Hägglöf ◽  
Martin Schmelz ◽  
Torsten Gordh
Keyword(s):  
Neuropathic Pain ◽  
Clinical Symptoms ◽  
Control Level ◽  
New Drugs ◽  
Spontaneous Pain ◽  
Double Blind ◽  
Clinical Model ◽  
Analgesic Effects ◽  
Proposed Model ◽  
Before And After

AbstractAimsSpontaneous and evoked pains are key symptoms of patients with neuropathic pain and there is a current discussion on the predictive value of evoked pain read outs for the reduction of spontaneous pain. Here we describe a new clinical model of neuropathic pain that may be useful for evaluation of new drugs. We also report the effects of lidocaine in this model as reference values.MethodsIn a randomized double-blind experiment, the analgesic effects of local lidocaine were investigated separately for spontaneous pain and for stimulus-evoked allodynia and hyperalgesia in sixteen patients with painful neuromas after traumatic nerve injuries in the upper extremities. The patterns of sensory changes were compared before and after treatment with lidocaine (0.1% or 0.5%, 1 ml), with 1–2 weeks interval, injected close to the neuroma. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS) and quantitative/qualitative sensory testing.ResultsLidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 90% with maximum effects between 1 and 5 min for evoked pain and between 3 and 15 min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20 minutes after the injection spontaneous pain levels were lower than 25% at this time. Moreover, in 4 patients the reduction of ongoing pain lasted 24 h whereas evoked pain had returned to baseline levels in all the patients after 1 h.ConclusionDifferential analgesic effects of local lidocaine on spontaneous and evoked pain suggest that different mechanism underlie these two key clinical symptoms. Thus, clinical trials assessing localized traumatic neuropathic pain should investigate both aspects of pain separately with the proposed model allowing testing of new drugs systemically or locally administered.

Does experimental pain response vary across the menstrual cycle? A methodological review

2006 ◽  
Vol 291 (2) ◽  
pp. R245-R256 ◽  
Author(s):  
Jeffrey J. Sherman ◽  
Linda LeResche
Keyword(s):  
Sex Differences ◽  
Menstrual Cycle ◽  
Pain Sensitivity ◽  
Experimental Pain ◽  
Pain Response ◽  
Methodological Review ◽  
Pain Stimulus ◽  
Hormonal Cycle ◽  
Methodological Problems ◽  
Pain Stimuli

The findings on sex differences in human experimental pain research are inconsistent. One possible factor contributing to the inconsistent findings is the female hormonal cycle, as hormone levels may affect pain sensitivity. A number of studies suggest that women's responses to experimentally evoked pain vary across the menstrual cycle. However, at least an equal number of studies suggest a lack of variability. The purpose of this article is to review the literature with emphasis on what we believe could be the reasons for the inconsistent findings, namely, differences in populations sampled, timing of experimental sessions across the menstrual cycle, and nomenclature used to identify the time (phases) in the cycle when measurements were done, nature of the pain stimuli chosen, and outcomes measured. These inconsistencies and other methodological problems associated with most experimental pain studies make it difficult to draw inferences from this literature. For the science to improve, replication of significant findings using standardized timing of sessions, pain stimulus procedures, outcomes, and hormonal assessment is necessary.

Pharmacodynamics of Orally Administered Sustained- release Hydromorphone in Humans

2001 ◽  
Vol 94 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Martin S. Angst ◽  
David R. Drover ◽  
Jörn Lötsch ◽  
Bhamini Ramaswamy ◽  
Sujata Naidu ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Sustained Release ◽  
Analgesic Effect ◽  
Time Course ◽  
Plasma Concentrations ◽  
Experimental Pain ◽  
Immediate Release ◽  
Double Blind ◽  
Sustained Release Formulation ◽  
Analgesic Effects

Background The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. Methods Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. Results The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. Conclusion A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.

A New Model of Electrically Evoked Pain and Hyperalgesia in Human Skin

2001 ◽  
Vol 95 (2) ◽  
pp. 395-402 ◽  
Author(s):  
Wolfgang Koppert ◽  
Sara K. Dern ◽  
Reinhard Sittl ◽  
Sven Albrecht ◽  
Jürgen Schüttler ◽  
...  
Keyword(s):  
Time Course ◽  
Rating Scale ◽  
High Current Density ◽  
Experimental Pain ◽  
Numeric Rating Scale ◽  
Human Model ◽  
High Temporal Resolution ◽  
Double Blind ◽  
New Model ◽  
Analgesic Effects

Background The authors used the analgesics alfentanil, S(+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia. Methods Transcutaneous electrical stimulation at a high current density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)-ketamine, and lidocaine were applied for 20 min in a double-blind, placebo-controlled, crossover design in 12 subjects using target controlled infusions. Results In the placebo session, pain ratings and areas of hyperalgesia were stable during the stimulation period, which facilitated the assessment of analgesic effects. Alfentanil effectively inhibited electrically evoked pain and reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine-induced inhibition of secondary hyperalgesia was more pronounced and lasted for the whole experimental protocol. Therapeutic levels of systemic lidocaine showed only marginal analgesic effects, but lasting antihyperalgesic effects. Conclusions A new model of electrically induced pain and hyperalgesia was established, which enabled assessment of the time course of analgesic and antihyperalgesic effects with high temporal resolution and minimum tissue damage and which was further validated by use of common intravenous anesthetics.

scholarly journals A 5-HT Antagonist (UP 26-91) versus Codeine and Placebo in a Human Experimental Pain Study

2000 ◽  
Vol 5 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Lars Arendt-Nielsen ◽  
Poul Pedersen ◽  
Lars Poulsen ◽  
Ole Kæseler Andersen ◽  
Peter Bjerring ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Pain Threshold ◽  
Statistical Significance ◽  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Double Blind ◽  
Stimulus Response ◽  
Pressor Test ◽  
Pain Models

BACKGROUND: This double-blind, randomized, crossover study compared the potential analgesic effect of the serotonin receptor antagonist UP 26-91 (50 mg, 150 mg and 300 mg) with that of codeine (100 mg) and placebo by use of different human experimental pain models.SUBJECTS AND METHODS: In experiment 1, pain detection and tolerance thresholds to heat, pressure and pain ratings during the cold pressor test were measured. In experiment 2, the pain threshold to single and repetitive (temporal summation) electrical sural nerve stimulation, and the pain intensity on a visual analogue scale to supra pain threshold electrical stimulation (stimulus-response-function) were measured. Tests were performed before, and 1, 2 and 6 h after drug administration.RESULTS: UP 26-91 did not show a marked effect on the experimental pain tests. Most of the variables tended to show a better effect from codeine than from placebo, but statistical significance for peak pain was only reached during the cold pressor test (P=0.011).CONCLUSIONS: In the present doses, the serotonin antagonist UP 26-91 had no effect on the experimental pain models applied.

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