CYCLOOXYGENASE (COX)-2 is constitutively expressed in the superficial dorsal horn of the spinal cord, but its role in the spinal cord is still unclear. We examined the effect of intrathecally administered NS398, a selective COX-2 inhibitor and indomethacin, an non-selective COX-1 and COX-2 inhibitor, on the development of thermal hyperalgesia induced by the activation of NMDA or AMPA receptors. Intrathecal injection of either NS398 or indomethacin equally blocked the development of thermal hyperalgesia induced by intrathecal injection of either NMDA or AMPA in a dose-dependent manner. These data suggest that COX-2 plays an important role in spinal thermal nociceptive transmission when neurons in the spinal cord are facilitated by NMDA or AMPA.