Corticotropin-releasing factor (CRF) plays important physiological functions in the central nervous system. The present study was performed to investigate the role of CRF and CRF receptor in nociceptive modulation in the central nucleus of amygdala (CeA) of rats. The hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation increased significantly after intra-CeA administration of 0.1 and 0.01nmol of CRF, but not 0.001nmol, indicating that CRF induces antinociceptive effects in the CeA of rats. The antinociceptive effect of CRF was attenuated by intra-CeA administration of 0.1nmolα-hCRF9-41, a selective CRF receptor antagonist, suggesting that the CRF-induced antinociception is mediated by the CRF receptors in the CeA. Furthermore, the HWL to both thermal and mechanical stimulation decreased significantly after intra-CeA administration of-αhCRF9-41 alone, suggesting an involvement of endogenous CRF in the CeA in nociceptive modulation. The present study demonstrated that both exogenous and endogenous CRF plays an antinociceptive effect in the CeA, the effect is mediated by CRF receptor.