Corticotropin-releasing factor inhibits the response of trigeminal neurons to noxious heat

In a previous study we reported that human/rat corticotropin-releasing factor (CRF) displayed antinociceptive activity in the mouse abdominal constriction assay. In this investigation we examined the effects of CRF on the evoked response of wide dynamic range (WDR) trigeminal neurons to noxious heat. Single units were recorded from the spinal trigeminal nucleus of urethane anesthetized rats. CRF inhibited the evoked response of these units in a dose-dependent manner with an ED50 of 2.3-7 nmol/kg i.v. Neither naloxone nor chlorisondamine pretreatment prevented the inhibitory actions of CRF. CRF-induced inhibition was also present in adrenalectomized and hypophysectomized animals. Intracerebroventricular administration of CRF did not inhibit the heat evoked response of WDR trigeminal units. alpha-Helical CRF, a CRF receptor antagonist, 12 nmol/kg i.v., alone did not affect the response of trigeminal units to heat, but pretreatment of animals with this dose blocked the inhibitory actions of CRF. By contrast to the inhibitory effects of CRF on heat-responsive units, CRF, 6-18 nmol/kg i.v., increased the spontaneous discharge rate of cold-responsive units by 57 +/- 16%. The data show that CRF selectively inhibits neuronal responses to noxious heat, an action that is independent of the pituitary-adrenal axis. These results are viewed as further evidence that CRF has antinociceptive properties in the periphery.