The analgesic effect of codeine as compared to imipramine in different human experimental pain models
Thomas P. EnggaardLars K. PoulsenLars Arendt‐NielsenSteen Honoré HansenInga BjørnsdottirLars F. GramSøren H. Sindrup
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The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection/tolerance thresholds to single electrical sural nerve stimulation and pain summation at tolerance threshold to repetitive electrical sural nerve stimulation (temporal summation) and pain experienced during the cold pressor test, rated as peak pain intensity, pain average intensity and discomfort. Compared to placebo, imipramine significantly increased pressure pain tolerance threshold (P = 0.03) and increased pain tolerance threshold (P = 0.05) and pain summation threshold (P = 0.03), but not pain detection threshold to electrical stimulation. Imipramine did not cause significant changes in pain perception during the cold pressor test. Codeine significantly increased pressure pain tolerance threshold (P = 0.02), pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain summation threshold (P = 0.02) to electrical stimulation. In addition, codeine reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is concluded that both imipramine and codeine inhibit temporal pain summation, whereas only codeine reduces cold pressor pain. Pain summation may be a key mechanism in neuropathic pain. Imipramine has a documented effect on such pain conditions on temporal summation. The present study showed that codeine also inhibits temporal summation, which is in line with the clinical observations indicating that opioids relieve neuropathic pain.Keywords:
Cold pressor test
Pain tolerance
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Pain tolerance
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This study was aimed at finding a relationship between pain modulators in the blood and physiological pain in apparently healthy Nigerians. It also aimed at establishing a pilot study for finding reference values for plasma levels of substance P, serotonin and tryptophan for the first time among Nigerians. Volunteers were made up of 110 residents of Abuja, aged between 21 and 50 years. Cold pressor test was used to induce pain assessing pain intensity, threshold and tolerance. ELISA was used to assay for plasma substance P, serotonin and tryptophan. Pain parameters from cold pressor test were correlated with plasma pain modulators measured. Results from cold pressor test revealed pain intensity to be 5.79±0.25cm, pain threshold 28.77±2.32s and pain tolerance 143.62±24.39s. Blood plasma level of substance P was 116.52±20.53pg/mL, serotonin 454.18±30.16ng/mL and tryptophan 12.77±0.67μg/mL. There was negative correlation between pain threshold and plasma substance P, pain tolerance and plasma substance P and pain threshold and plasma serotonin. There was however a positive correlation between pain intensity and plasma serotonin. In conclusion, the regression formulas may aid in using cold pressor test to predict blood substance levels of the measured pain modulators in a low resource setting like Nigeria where ELISA test is very expensive.
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Nigerians
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The aims of the present study were to investigate the influence of anxiety on pain perception and to test whether gender differences in pain perception are anxiety dependent. Sixty male and female university students exposed to situation-evoked anxiety or a control procedure were measured for their pain threshold, tolerance, and perceived intensity during a cold pressor test. Both subjective and autonomic responses indicated that anxiety was successfully induced in participants exposed to the anxiety condition. Increased situational anxiety had no significant effect on pain threshold or pain tolerance. Significant increases in pain intensity were found for the anxiety group. Levels of anxiety, however, did not correlate with this increased intensity, raising doubt as to the role of anxiety in producing this effect. No gender differences were found for pain tolerance or pain intensity. Gender differences were found for pain threshold in the anxiety group with, contrary to past findings, females showing significantly higher pain thresholds than males. The results are discussed in the light of related studies.
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Pain Perception
Test anxiety
Intensity
Situational ethics
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In animal models, allopregnanolone (ALLO) negatively modulates the hypothalamic–pituitary–adrenal (HPA) axis and has been shown to exert analgesic effects. The purpose of this study was to assess the relationship between plasma ALLO immunoreactivity (ALLO-ir), HPA-axis measures, and pain sensitivity in humans. Forty-five African Americans (21 men, 24 women) and 39 non-Hispanic Whites (20 men, 19 women) were tested for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests. Plasma ALLO-ir, cortisol, and β-endorphin concentrations were taken following an extended rest period. Lower concentrations of ALLO-ir were associated with increased pain tolerance to all three pain tests and increased pain threshold to the thermal heat pain task in the non-Hispanic Whites only (rs = −.35 to −.49, ps < .05). Also, only in the non-Hispanic Whites was cortisol associated with thermal heat tolerance (r = +.39, p < .05) and threshold (r = +.50, p < .01) and cold pressor tolerance (r = +.32, p < .05), and were β-endorphin concentrations associated with cold pressor tolerance (r = +.33, p < .05). Mediational analyses revealed that higher cortisol levels mediated the relationship between lower ALLO-ir and increased thermal heat pain threshold in the non-Hispanic Whites only. These results suggest that lower ALLO-ir concentrations are associated with decreased pain sensitivity in humans, especially in non-Hispanic Whites, and that this relationship may be mediated by HPA-axis function.
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In the present study the question was addressed whether sensitivity to experimental pain stimuli differs between families, which are previously characterized by the degree of cold tolerance (very insensitive or very sensitive) of one family member. A total of 232 healthy medical students were screened for cold pain tolerance employing a cold pressor test. Subsequently 50 of them were investigated in detail under laboratory conditions. The water temperature was 1 degrees C, the maximum time in water 3 min, cold pain was rated on a 101 step numerical rating scale every 10s. Two of the most cold pain sensitive (shortest time in ice water) and insensitive (lowest ratings) students were selected and as many as possible of their family members were recruited. In all of them cold pressor test, pinprick pain threshold, pressure pain threshold, skin temperature, hospital anxiety and depression scale and COMT val158met polymorphism (with the exception of three individuals) were assessed. Analysis (ANOVA) revealed that the cold pressor results of the students predicted the mean ratings (p<0.04) and the time in ice water (p<0.03) of their own families. Furthermore, pinprick pain threshold (p<0.002) and to a lesser extent pressure pain thresholds (p<0.03) were significantly related to cold pain tolerance. The other variables, including the COMT polymorphism, were not related to cold pain tolerance in our study. In conclusion our results suggest that cold pain tolerance may be at least partially inherited. Genetic or environmental factors might explain family clustering of cold pain sensitivity.
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The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection/tolerance thresholds to single electrical sural nerve stimulation and pain summation at tolerance threshold to repetitive electrical sural nerve stimulation (temporal summation) and pain experienced during the cold pressor test, rated as peak pain intensity, pain average intensity and discomfort. Compared to placebo, imipramine significantly increased pressure pain tolerance threshold (P = 0.03) and increased pain tolerance threshold (P = 0.05) and pain summation threshold (P = 0.03), but not pain detection threshold to electrical stimulation. Imipramine did not cause significant changes in pain perception during the cold pressor test. Codeine significantly increased pressure pain tolerance threshold (P = 0.02), pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain summation threshold (P = 0.02) to electrical stimulation. In addition, codeine reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is concluded that both imipramine and codeine inhibit temporal pain summation, whereas only codeine reduces cold pressor pain. Pain summation may be a key mechanism in neuropathic pain. Imipramine has a documented effect on such pain conditions on temporal summation. The present study showed that codeine also inhibits temporal summation, which is in line with the clinical observations indicating that opioids relieve neuropathic pain.
Cold pressor test
Pain tolerance
Summation
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Pain tolerance
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Repeated measures design
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Abstract Background The cold pressor task ( CPT ) was originally developed as a clinically indicative cardiovascular test, and quantifies vascular response and pulse excitability when a subject's hand is immersed into ice water. Since the test procedure results in a gradually increasing cold pain, the CPT has been widely used as a nociceptive stimulus in experimental studies on adults and children. Aim To evaluate the test‐retest stability of response patterns using the CPT as a measure of pain threshold and pain tolerance. Materials and Methods In the present study, sixty‐one undergraduate students received painful stimulation using the CPT either at 4°C or 6°C. Measurements of pain threshold, pain tolerance and pain intensity ratings using the short form of the M c G ill pain questionnaire ( SF ‐ MPQ ), were derived. The assessment was repeated twice over an interval of 2 weeks. Test‐Retest stability was assessed within a three‐layered approach, using ANOVA s, interclass correlation coefficients and standard error of the mean. A B land‐ A ltman analysis was also performed. Possible predictors of pain threshold and pain tolerance were assessed using random effect panel regression models. Results No significant differences emerged as a function of temperature (4°C or 6°C) on pain threshold, pain tolerance, and pain ratings. Environmental variables (room temperature and humidity) show no impact on measures of pain threshold and pain tolerance. Conclusion Consistent with previous findings, regression analysis reveals that age is significantly associated with pain tolerance. The CPT procedure shows excellent 2 week test‐retest stability to assess pain threshold and pain tolerance within a student population.
Cold pressor test
Pain tolerance
Repeated measures design
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