Delayed activation of nociceptors: correlation with delayed pain sensations induced by sustained stimuli

Abstract

1. In this study we used psychophysical experiments in humans and behavioral and electrophysiological studies in rats to evaluate nociceptive and C-fiber mechanoheat nociceptor (C-MH) responses to sustained mechanical stimuli that are initially nonpainful or nonnoxious. 2. In normal rat skin, sustained subthreshold mechanical stimuli activate C-MHs (n = 36) with a delayed onset that parallels the delayed pain sensation recorded in human psychophysical tests. 3. The subthreshold stimuli did not induce a decrease in mechanical threshold (n = 11), and the effect of the subthreshold stimulus on latency to firing of C-MHs (n = 6) persists for a very short time after the stimulus is removed (less than 10 s). 4. Intradermal injection of prostaglandin E2 (PGE2; 100 ng), which induced a significant decrease in the mechanical threshold of C-MHs (n = 7), had no effect on the latency of the delayed activation of C-MHs. Also, indomethacin, which inhibits the synthesis of prostaglandins, had no effect on the latency of the delayed paw-withdrawal response in the behavioral test. 5. Intradermal injection of the calcium ionophore A23187 significantly reduced the latency of the delayed activation of C-MHs (n = 6) the calcium chelator Quin 2 (n = 6) significantly increased the latency. A23187 and Quin 2 had similar effects on the latencies to paw withdrawal in behavioral tests. The sensitization of C-MHs (n = 9) by PGE2 was not, however, affected by Quin 2.(ABSTRACT TRUNCATED AT 250 WORDS)