The focus of this project is to determine the basic neural mechanisms that mediate muscle pain and deep hyperalgesia. The specific aims are to compare psychophysical measures of muscle pain and hyperalgesia in humans to evoked responses of single human muscle afferents and spinal dorsalhorn neurons recorded in anesthetized monkeys, using similar stimuli. Muscle pain will be produced by intramuscular injection of the irritant capsaicin, and by direct intraneural electrical stimulation. Following injection of capsaicin (0.01-100 mg) into the gastrocnemius- soleus muscle, in humans, the quality, magnitude and duration of spontaneous pain and hyperalgesia to gentle pressure of these muscle will be assessed. These results will provide information about the capacity of humans to scale the magnitude of deep pain. In electrophysiological studies in humans, single nociceptive muscle afferents from the common peroneal nerve will be identified, and stimulus-response characteristics determined through combined intraneural stimulation and recording. Capsaicin will be injected into their receptive field and estimates of pain magnitude and evoked afferent activity will be recorded simultaneously. Judgments of pain induced by pressure will be compared to simultaneously evoked responses before and after injection. In additional studies, trains of electrical stimuli will be delivered intraneurally at different frequencies. Subjects will map the area of deep projected pain and estimate the magnitude of evoked pain. This will give information regarding encoding properties of human muscle nociceptors. In anesthetized monkeys,recordings will be made from spinothalamic tract (STT) cells with receptive fields innervating the gastrocnemius-soleus muscle. Receptive field area, spontaneous activity and responses to quantitative mechanical stimulation of muscle will be obtained before and after intramuscular injections of vehicle and capsaicin. Discharges of STT cells evoked by capsaicin and by mechanical stimuli will be compared to the magnitude of pain and mechanical hyperalgesia in humans produced by identical stimuli. These studies will be the first to determine stimulus-response characteristics of human muscle nociceptors and to compare their activity and activity of spinal neurons, with psychophysical measures of muscle pain. Results will provide new knowledge concerning neural mechanisms of muscle pain, as well as insight into pathophysiology of muscle pain syndromes associated with injury or disease.