This project uses both patients and normal volunteers to investigate the activation and maintenance of mechanisms responsible for central enhancement of spontaneous and evoked pain. Two patients with persistent localized inflammatory disease were examined and particularly painful foci (4 to 5) were each injected with 0.1 to 0.2 ml of 2 % lidocaine. During the 20 min of anesthesia, spontaneous pain was reduced or abolished, and touch applied to previously painful, unanesthetized areas was perceived as touch and not as pain. This result and similar results in 4 patients last year further confirms our model of altered central processing maintained by input from nociceptors and supports the concept that the variety of syndromes may reflect the various means by which this input may be achieved. Previous findings in patients suggest that focal input from a specific nerve territory can result in allodynia and spontaneous pain in the territory of afferent peripheral nerve, a finding that has often resulted in a psychiatric diagnosis. A series of radial and ulnar nerve blocks defined the extent of these nerve territories in the dorsum of the hand in 12 subjects. Intradermal injection of capsaicin into the ulnar distribution resulted in allodynia and secondary hyperalgesia in the radial nerve distribution, confirming clinical findings and consistent with our hypothesis that allodynia and other effects result from a central mechanism. Three studies of 10 subjects each showed that electrically- evoked sensations are reliable even when the electrodes are removed and reapplied, validating this important technique. An intradermal capsaicin injection facilitated temporal summation in 10 subjects, implicating summation mechanism in clinical conditions of central hyperexcitability. A study (n=10) of the influence of innocuous A beta stimulation was inhibitory when delivered before capsaicin induced facilitation of the nociceptive reflex found that A beta stimulation was inhibitory when delivered before capsaicin intradermal injection and excitatory when delivered after the injection. These effects represent both classic """"""""Gate Control"""""""" pain inhibition and the novel finding that once initiated, altered central processing can be maintained by input from touch fibers. New studies will examine the duration of pain sensations produced by heat applied to the zone of allodynia, the effect of trains of thermal and electrical stimulation applied to this zone, and use a nociceptive reflex to measure A beta maintenance of central summation.