Peripheral neural mechanisms of cutaneous hyperalgesia following mild injury by heat

Pain thresholds in humans were determined for heat stimulations of the skin before and after a mild injury induced by a single conditioning stimulus (CS) of 50 degrees C and 100 sec duration. The same stimuli were delivered to the receptive fields of C fiber and A fiber mechanoheat-sensitive nociceptors (CMH and AMH nociceptors, respectively) and of low threshold warm and cold receptors in the anesthetized monkey and to the receptive fields of CMH nociceptors recorded percutaneously from the peroneal nerve of awake humans. Pain thresholds in normal skin were matched only by the response thresholds of CMH and not AMH nociceptors. Immediately following heat injury, some pain thresholds and CMH response thresholds were elevated, but by 5 to 10 min after the CS, pain and CMH thresholds were lowered to 2 to 6 degrees C below normal (hyperalgesia and nociceptor sensitization). No other type of cutaneous receptor studied exhibited changes in threshold similar to those observed for pain and for CMH nociceptors. The magnitude of hyperalgesia in humans and the magnitude of sensitization of CMH nociceptors in monkeys following heat injury were greater for hairy than for glabrous skin. The time course of the development of hyperalgesia was not altered by ischemia or conduction block in A fibers. The results support the conclusion that altered activity in CMH nociceptors is a major peripheral determinant of cutaneous hyperalgesia following a mild heat injury to the skin.