Articles: hyperalgesia.
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1. The effect of IL-4 on responses to intraplantar (i.pl.) carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8 and PGE2 was investigated in a model of mechanical hyperalgesia in rats. Also, the cellular source of the IL-4 was investigated. 2. ⋯ These data suggest that IL-4 released by mast cells limits inflammatory hyperalgesia. During the early phase of the inflammatory response the mode of action of the IL-4 appears to be inhibition of the production TNFalpha, IL-1beta and IL-8. In the later phase of the response, in addition to inhibiting the production of pro-inflammatory cytokines, IL-4 also may inhibit the release of PGs.
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Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, and an increase in responses evoked by large and small caliber primary afferent fibers. Sensitization of dorsal horn neurons often occurs following tissue injury and inflammation and is believed to contribute to hyperalgesia. Windup refers to the progressive increase in the magnitude of C-fiber evoked responses of dorsal horn neurons produced by repetitive activation of C-fibers. ⋯ Enhanced responsivity to C-fiber input following windup produced by stimulation inside the RF at a frequency of 0.5 Hz could be maintained for approximately 100 s by stimuli delivered at 0.1 Hz, a frequency that itself cannot produce windup. It is concluded that neuronal events leading to windup also produce some of the classical characteristics of central sensitization including expansion of RFs and enhanced responses to C- but not A-fiber stimulation. Thus, windup may be a useful tool to study mechanisms underlying certain characteristics of central sensitization related to C-fiber activity.
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Preclinical and clinical evidence indicates that locally administered opioid agonists produce an antihyperalgesic effect through peripheral opioid receptors in inflamed tissue. Loperamide, a mu opioid agonist, does not cross the blood-brain barrier and therefore lacks central effects after systemic administration. The authors defined the effects of topical loperamide on a thermal injury-induced hyperalgesia. ⋯ Loperamide, a peripherally acting mu opioid agonist, applied topically at the site of inflammation possesses a significant antihyperalgesic action without any systemic side effects.
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The hypothesis that prostaglandins contribute to hyperalgesia resulting from nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. Subcutaneous injection of indomethacin (a classic inhibitor of cyclo-oxygenase) into the affected hindpaw relieved mechanical hyperalgesia for up to 10 days after injection. Subcutaneous injection of meloxicam or SC-58125 (selective inhibitors of cyclo-oxygenase-2) into the affected hindpaw also relieved mechanical hyperalgesia, but with a shorter time-course. ⋯ Comparable injections into the contralateral paw or abdomen had no effect on mechanical or thermal hyperalgesia, suggesting that the effects we observed were local rather than systemic. We conclude that prostaglandins, probably prostaglandin E1 or E2, contribute to the peripheral mechanisms underlying hyperalgesia following nerve injury. These data provide further evidence that inflammatory mediators contribute to neuropathic pain, and may warrant further study of peripherally administered non-steroidal anti-inflammatory drugs as a possible treatment for such pain in patients.
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Flare and hyperalgesia after intradermal capsaicin injection in human skin. J. Neurophysiol. 80: 2801-2810, 1998. ⋯ It is inferred that the cutaneous nerve fibers responsible for the thermographic flare branch, or have coupled axons, over a long distance. The large area of flare coincided with the area of mechanical and heat hyperalgesia. Equivalence of the areas of flare and mechanical and heat hyperalgesia induced by intradermal capsaicin injection suggests that all three phenomena are the consequence of neural factors that operate peripherally.