Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor.

Prostaglandins are now thought to play an important role in nociceptive information transmission in the spinal cord. Prostaglandins are known to be produced by cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid. Two forms of COX have been identified: COX-1, which is constitutively expressed in most tissues and organs, and COX-2, which is an inducible enzyme and is localized primarily in inflammatory cells and tissues. COX-2 mRNA has been reported to be expressed in the brain in normal rats. We investigated the role of COX-1 and COX-2 in the spinal nociceptive transmission during the rat formalin test and the hot plate test using indomethacin, a non-selective COX-1 and COX-2 inhibitor, and NS398, a selective COX-2 inhibitor. In the formalin test, drugs were administered intrathecally or intraperitoneally 10 min before (pre-treatment study) or 7 min after (post-treatment study) the formalin injection. Both intrathecally administered indomethacin and NS398 inhibited the formalin induced flinching behavior in a dose-dependent manner in the pre-treatment study, but not in the post-treatment study. Both indomethacin and NS398 had no effect on the hot plate test at a dose which depressed the formalin induced flinching behavior. These data suggested that COX-2 is expressed in the central nervous system, including the spinal cord, and that COX-2 plays an important role in the spinal nociceptive transmission during the formalin test, but not during the hot plate test.