The long term objective of this research is to understand the mechanism of pain in pathological pain states and develop better strategies for controlling pain. Studies from this laboratory, and others, have demonstrated that the hyperalgesia which follows tissue injury is based, in part, on sensitization of nociceptor. This sensitization results from the modulation of nociceptor response by chemical mediators of inflammation. Recent behavioral studies indicate that the administration of opiates at the site of injury in rats leads to inhibition of the hyperalgesic response by a specific opiate receptor-mediated mechanism. We will determine, using single fiber recordings from primary nociceptive afferents in monkey if opiates can inhibit the sensitization of nociceptor following injury. Clinical evidence also indicates an important role of the sympathetic nervous system in pain states resulting from trauma, with or without associated peripheral nerve injury (e.g., causalgia and reflex sympathetic dystrophy). The development of excitatory adrenergic receptors in regenerating c- and A delta - fibers in an injured nerve provides a possible mechanism for causalgia. Though an alpha-receptor mediated mechanism is postulated, the receptor subtype(s) involved have not been determined. In addition, A-fiber nociceptive afferents are activated by stimulation of the sympathetic nervous system after (but not before) tissue injury. The role of the sympathetic nervous system in modulating nociceptor responsiveness following injury will be determined by studying the effects of adrenergic agonists on activity of nociceptor that innervate injured skin, and on C- and A delta- fibers from neuromas in monkey. Selective adrenergic receptor antagonists will be used in inhibit the adrenergic sensitivity of the nociceptive afferents and to characterize the receptor subtypes involved. An understanding of the chemosensitivity of nociceptive afferents following cutaneous or nerve injury may lead to better pharmacological therapies to alleviate pain.
Showing the most recent 10 out of 88 publications