To understand the mechanisms of CRF-induced analgesia we investigated a contribution of hypothalamic-pituitary-adrenocortical (HPA) axis (which is activated by CRF through CRF-1 receptor subtype) as well as CRF-2 receptor subtype and opioid system in the analgesic effect of CRF. The contribution of HPA axis was studied by its pharmacological suppression as well as an occupation of glucocorticoid receptors by its antagonist RU 38486. The opioid antagonist naltrexone and CRF-2 receptor antagonist astressin 2-B were used to examine the involvement of opioid system and CRF-2 receptor subtype, respectively. Electrical current threshold test was used for measurement of the somatic pain sensitivity in anesthetized rats. Both systemic and central CRF administration caused an analgesic effect and an increase in blood corticosterone level. Pretreatment by naltrexone had no effect on the analgesic effect of systemic or central CRF. Pharmacological suppression of HPA axis, leading to an inability of CRF, ACTH and corticosterone release, resulted in a decrease or an elimination of analgesic effect of systemic or central CRF, respectively. Analgesic effect of CRF caused by systemic as well as central CRF was partly abolished by glucocorticoid receptor antagonist RU-38486. CRF-2 receptor antagonist astressin 2-B completely eliminated analgesic effect induced by systemic CRF. The data obtained suggest that the analgesic effect of CRF on somatic pain sensitivity in anesthetized rats was mediated by non-opioid mechanisms. CRF-induced analgesia observed in these conditions may be provided by mechanisms: 1) associated with HPA axis and mediated through glucocorticoid receptors and 2) mediated through CRF-2 receptors. Supported by grants RFBR N 09- 04–00964, FNM-2009, DBS RAS(2008), SS- 1434.2008.4.