Pain
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Recently, it has been reported that loosely constrictive chromic gut ligatures around the sciatic nerve produce behavioral evidence of neuropathic pain in rats. It has been shown that axonal swelling after ligation results in a constriction injury associated with a decrease in the number of both large-diameter myelinated and small-diameter unmyelinated axons, but the mechanism(s) producing spontaneous pain and thermal hyperalgesia remain largely unknown. The present study systematically evaluated potential mechanisms involved in development of the behavioral changes produced by chromic gut ligatures loosely tied around the sciatic nerve. ⋯ These postural changes were most pronounced in the 2-0 and 3-0 chromic gut-treated rats. Chromic gut sutures (4-0, 3-0, or 2-0) tied loosely around the left sciatic nerve also produced a 'dose-dependent' decrease in thermal withdrawal latency that was maximal on postoperative day 3 (25%, 39%, and 41%, respectively). The magnitude of the thermal hyperalgesia declined over time such that a return to baseline was observed by postoperative day 20 in 4-0 and 3-0 chromic gut-treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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Comparative Study
Sex differences in responsiveness to painful and non-painful stimuli are dependent upon the stimulation method.
Sex differences in thermo- and electrocutaneous responsiveness to painful and non-painful stimuli were investigated in 20 women and 20 men. Heat pain, warmth, and cold thresholds were assessed on the hand and foot with a Peltier thermode system. In addition, subjects used magnitude estimation to judge the sensation intensity evoked by temperatures ranging from 38 degrees C to 48 degrees C applied to the forearm. ⋯ In contrast, no significant correlations between the methods were found when considering the responsiveness to non-painful stimuli. The findings help to clarify controversies in the pain literature about sex differences. Results affirming and denying such differences could be obtained within a single sample, with stimulation method as the critical variable.
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An investigation was conducted to examine both temporal and spatial factors likely to be involved in spinal cord nociceptive coding by wide cord nociceptive neurons. Three separate methodologies were employed. First, the impulse frequency responses of L4 spinal cord wide-dynamic-range (WDR) neurons to gentle mechanical stimulation, vigorous but innocuous brushing, warmth (43 degrees C), and nociceptive thermal stimuli (45-49 degrees C) were electrophysiologically characterized in unanesthetized, spinal cord-transected rats. ⋯ With stimulus frequency held constant at 50 Hz, low stimulus currents, sufficient to activate only small numbers of ALQ axons, produced innocuous sensations. Higher stimulus currents, sufficient to activate larger numbers of neurons, consistently produced painful sensations. Increasing ALQ stimulus frequency at currents subthreshold for pain or increasing stimulus currents at frequencies subthreshold for pain resulted in painful sensations, thus indicating that both discharge frequency and numbers of neurons activated are both important factors in the encoding of pain.(ABSTRACT TRUNCATED AT 400 WORDS)
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It has recently been shown that O-demethylation of the opioid drug codeine to morphine depends on the sparteine/debrisoquine oxygenase (CYP2D6) which in man exhibits genetic polymorphism. Morphine may be an endogenously formed substance in mammalians. Therefore, it may be hypothesized that the final step in an endogenous synthesis of morphine from codeine also depends on CYP2D6. ⋯ However, for the cold pressor test, peak pain ratings and area under the pain rating-time curve during 2 min were significantly higher in poor than in extensive metabolisers (P = 0.0024 and 0.044). Furthermore, a substantially higher fraction of poor metabolisers prematurely withdrew their hand from the ice water during the cold pressor test due to intolerable pain (32 vs. 18%, P = 0.0545). We conclude that poor metabolisers of sparteine may be less tolerant to tonic pain than extensive metabolisers, and we hypothesize that this may be related to an inherited defect in endogenous synthesis of morphine via CYP2D6 in the brain.
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This study evaluated the antinociceptive effects of systemically administered selective opioid agonists of mu (DAMGO), delta (BUBU) and kappa (U 69593) receptors on the vocalization threshold to paw pressure in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. DAMGO (0.5-2 mg/kg), BUBU (1.5-6 mg/kg) and U 69593 (0.75-3 mg/kg) injected intravenously (i.v.) produced a potent long-lasting antinociceptive effect on both hind paws. ⋯ The present data clearly show that an acute i.v. injection of these selective opioid agonists induces potent antinociceptive effects in a rat model of peripheral neuropathy. These data are discussed with regard to the classical view that there is opioid resistance in neuropathic pain.