Delayed activation of nociceptors: correlation with delayed pain sensations induced by sustained stimuli.
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)
White
D M
DM
Department of Medicine, University of California, San Francisco 94143.
Taiwo
Y O
YO
Coderre
T J
TJ
Levine
J D
JD
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time; D012684:Sensory Thresholds / Q000187:drug effects; D012867:Skin / Q000294:innervation
D000634:Aminoquinolines; D011458:Prostaglandins E; D000001:Calcimycin; C035739:Quin2; D007213:Indomethacin