Involvement of corticotropin-releasing factor in the antinociception produced by interleukin-1 in mice

Recombinant human interleukin-1 alpha (rHu-IL-1 alpha) has been indicated to produce central antinociception in the mouse phenylquinone writhing test, the antinociception being unaffected by naloxone. Because interleukin-1 has been demonstrated to be a potent releaser of corticotropin-releasing factor (CRF) from the hypothalamus, we were interested to see whether CRF is involved in the antinociception induced by rHu-IL-1 alpha. In the present study, we examined this question using the mouse phenylquinone writhing test, in which mice were injected with various doses of CRF and/or alpha-helical CRF-(9-41), a CRF antagonist. CRF inhibited writhing responses after i.v. and intracisternal (i.c.) administration. The antinociception elicited by i.v. administered CRF was antagonized by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). The antinociception elicited by i.e. administered CRF was antagonized by i.c. injection of alpha-helical CRF-(9-41) and s.c. treatment of opioid antagonists. rHu-IL-1 alpha-induced antinociception was attenuated by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). These findings suggest that CRF possesses antinociceptive efficacy by both peripheral and central mechanisms, and that the antinociception induced by rHu-IL-1 alpha is mediated, at least in part, by the peripheral action of CRF.