Low but not high rat noxious radiant skin heating evokes a capsaicin-sensitive increase in spinal cord dorsal horn release of substance P

Some kinds of nociception appear to be partially mediated by the release of substance P (SP) in the spinal cord dorsal horn from terminals of primary afferent nociceptors. Only some nociceptors contain and release SP however. Specifically, SP appears to be released by unmyelinated (C) nociceptive afferents when activated by noxious stimulation to the skin, but does not appear to be contained in cutaneous myelinated (A δ) nociceptive afferents. We have proposed a model of nociception in rats that uses different rates of noxious skin heating to allow for differential assessment on behavioral responses mediated by the activation of A δ or C fiber nociceptors. As one means of testing the validity of this model we have examined the effects of using high and low rate noxious skin heating on the dorsal horn release of substance P-like immunoreactivity (SPLI) in decerebrate/spinal transected animals. Consistent with the model, low rate skin heating evokes a significant increase in dorsal horn SPLI release indicating C fiber mediation, whereas high rate skin heating did not evoke SP release, indicating mediation by afferents other than C afferents, i.e. A δ nociceptive afferents. Also consistent with behavioral effects, topical application of capsaicin, which sensitizes C nociceptors, increased the SPLI release evoked by low but not high rate skin heating. These data provide additional evidence that foot withdrawals evoked by low rate skin heating are mediated by C fiber activation, whereas foot withdrawals evoked by high rate skin heating are evoked by A δ fiber activation.