Peripheral but not intracerebroventricular corticotropin-releasing hormone (CRH) produces antinociception which is not opioid mediated

Abstract

Corticotropin-releasing hormone and endogenous opioid peptide systems are both activated during stress. An elevation of the pain threshold also occurs under conditions of stress. In the present study the effects of CRH antinociception were examined. Rats were treated with CRH either centrally (i.c.v.) or peripherally (intracardially; i.c.) and their tail-flick latencies were measured. Central application of CRH (0-30 micrograms) was without effect on the analgesic test, while after peripheral application (0-32 micrograms) CRH produced a dose-dependent increase in tail-flick latencies. In a subsequent experiment we examined the possible involvement of endogenous opioids in the peripheral CRH-induced antinociceptive effects. To this end, two approaches were used: animals were either acutely treated with the opioid antagonist naloxone (3 or 6 mg/kg), or they were rendered tolerant to morphine, and then tested with CRH. In both cases, CRH effects on the tail-flick latencies were not modified. Our findings suggest that: (a) CRH may modulate pain sensitivity during stress; (b) opioids do not mediate this effect; and (c) brain CRH receptors are probably not involved in these processes.