Articles: hyperalgesia.
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Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that binds to the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). There is a large body of evidence supporting a role for TRPV1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded, doses of perineural RTX as a method for regional pain control. ⋯ Using a range of mechanical and thermal algesic tests, we found that the most sensitive measure following perineural RTX administration was inhibition of inflammatory hyperalgesia. Recovery studies showed that physiologic sensory function could return as early as two weeks post-RTX treatment, however, immunohistochemical examination of the DRG revealed a partial, but significant reduction in the number of the TRPV1-positive neurons. We propose that this method could represent a beneficial treatment for a range of chronic pain problems, including neuropathic and inflammatory pain not responding to other therapies.
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Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. ⋯ We found clear signs of sensitization of the trigeminal nociceptive system for at least one week after the surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization, which may play a role in the transition from acute to chronic pain in susceptible individuals.
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The heat pain threshold was assessed in 32 healthy participants after a mild burn on the dorsal surface of each hand, after injection of an opioid antagonist (80 microg naloxone) or vehicle alone (0.2 mL saline) into the burnt skin of 1 hand, and after repeated painful immersion of this hand in cold water for up to 180 seconds. We hypothesized that sensitivity to heat would decrease at the burn-injured site after the immersions, due to local release of opioids into the burnt skin. Naloxone augmented cold-induced pain during the immersions in participants who tolerated the longest immersions, implying that release of endogenous opioids suppressed cold-pain. After the immersions, sensitivity to heat decreased at the burn-injured site in the immersed hand, but naloxone did not block this effect. Instead, naloxone altered sensitivity to heat in unburnt skin, implying that thermal hyperalgesia at sites of burn injury masked the modulatory effects of opioids. In particular, naloxone blocked a decrease in sensitivity to heat at an unburnt site on the contralateral hand of participants who tolerated the longest immersions, consistent with central or systemic opioid release. Naloxone reduced sensitivity to heat at unburnt sites in participants who tolerated medium-length immersions, suggesting that an increase in systemic or central opioid activity evoked thermal hyperalgesia in this group. In addition, in a small group of participants who tolerated only brief immersions, naloxone blocked decreases in sensitivity to heat at an unburnt site in the immersed hand. These findings suggest that repeated painful immersions trigger local opioid release in participants who tolerate only brief immersions, and elicit central or systemic opioid release in participants who tolerate longer immersions. ⋯ This article demonstrates that repeated immersion of the hand in painfully cold water increases opioid activity and that the increase in opioid activity exerts multiple opposing effects on sensitivity to heat. Individual differences in the response to opioids might contribute to individual differences in pain tolerance.
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Streptozotocin-induced hyperglycemia accompanied by a chronic decrease in the nociceptive threshold is considered a useful model of experimental hyperalgesia. We examined (1) the effect of the opioid receptor agonists and (2) the effect of the magnesium ions (Mg(2+)) on the antinociceptive action of opioid agonists in a diabetic neuropathic pain model. ⋯ However, pretreatment with Mg(2+) at a dose of 40 mg magnesium sulfate/kg i.p. markedly enhanced the analgesic activity of all three investigated opioids. Practical aspects of co-administration of magnesium and opioids in diabetic neuropathy are discussed.
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Honeybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV) into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK) in the generation of BV-induced pain hypersensitivity. ⋯ The results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.