The present study was performed to investigate effects of central cyclooxygenase (COX) on interleukin (IL)-1beta-induced hyperalgesia in the orofacial area. Experiments were carried out on 72 male Sprague-Dawley rats weighing 220-280 g. Surgical procedures were performed under pentobarbital sodium. We examined noxious behavioral scratching responses induced by 50 mul of 5% formalin injected subcutaneously into the vibrissa pad without any restraints. The orofacial formalin responses exhibited two distinct phases with early responses (0-10 min) and continuous prolonged responses (11-45 min). Intracisternal injection of 100 pg IL-1beta significantly increased noxious behavioral responses. Pretreatment with indomethacin, a non-selective COX inhibitor, or NS-398, a selective COX-2 inhibitor, blocked IL-1beta-induced hyperalgesic responses. However, pretreatment with SC-560, a selective COX-1 inhibitor, did not change hyperalgesic response to IL-1beta. These data suggest that central IL-1beta modulates the transmission of nociceptive information in the orofacial area and that central COX-2 plays an important role in IL-1beta-induced hyperalgesia. (C) 2003 Elsevier Ireland Ltd. All rights reserved.