Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain associated with allodynia. Our preliminary experiments with FMS subjects have indicated abnormalities of second pain in these patients which are related to central N-methyl-D-aspartate (NMDA) receptor processing. Our basic hypothesis is that abnormal central pain processing of second pain in FMS subjects is one of the fundamental abnormalities in this syndrome. Second pain results from impulse conduction in peripheral C (unmyelinated) afferent axons and is particularly sensitive to inhibition by opioid compounds. Second pain also increases in intensity when stimuli are applied more often than once every three seconds and this summation has been hypothesized to result from a central NMDA receptor mechanism. First pain is related to stimulation of A-Delta (myelinated) nociceptors and has been utilized almost exclusively to evaluate pain sensitivity. In order to compare directly abnormal processing of A-Delta and C-Fiber input in FMS subjects, we will utilize forms of brief experimental pain stimuli that can reliably evoke perceptions of first and second pain when applied to the hand or foot of human subjects. We will test the hypothesis that oral doses of dextromethorphan, a common cough suppressant and NMDA receptor antagonist, will selectively reduce temporal summation of second pain for normal male and female subjects. The purpose of another experiment is to examine the effects of graded doses of naloxone and fentanyl on first and second pain and temporal summation of second pain for normal male and female subjects, This analysis is designed to answer questions about opioid mechanisms of pain reduction and about the possible existence of a tonic endogenous pain modulatory system. These psychophysical tests of NMDA receptor mechanisms, opioid responsiveness, and level of tonic pain inhibitory mechanisms will then be compared across pain-free control subjects and fibromyalgia patients in order to ascertain the extent to which abnormalities of these mechanisms contribute to these pain states. Potential sex differences in pain sensitivity and effects of pharmacological manipulations will be evaluated in normal subjects and pain patients, with attention to the impact of psychosocial variables. Also, relevant to the greater risk factor for females to present with fibromyalgia, ovarian hormone states will be monitored in female subjects. Because fibromyalgia is a generalized muscular pain disorder which characteristically worsens with physical activity, the effects of exercise on different forms of pain sensitivity will be compared for fibromyalgia patients and matched normal controls.
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