The acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugsand release of spinal prostaglandin E-2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1

Western blots show the constitutive expression of COX-1 and COX-2 in the ra t spinal dorsal and ventral horns and in the dorsal root ganglia. Using sel ective inhibitors of cyclooxygenase (COX) isozymes, we show that in rats wi th chronic indwelling intrathecal catheters the acute thermal hyperalgesia evoked by the spinal delivery of substance P (SP; 20 nmol) or NMDA (2 nmol) and the thermal hyperalgesia induced by the injection of carrageenan into the paw are suppressed by intrathecal and systemic COX-2 inhibitors. The in trathecal effects are dose-dependent and stereospecific. In contrast, a COX -1 inhibitor given systemically, but not spinally, reduced carrageenan-evok ed thermal hyperalgesia but had no effect by any route with spinal SP hyper algesia. Using intrathecal loop dialysis catheters, we showed that intrathe cal SP would enhance the release of prostaglandin E-2 (PGE(2)). This intrat hecally evoked release of spinal PGE(2) was diminished by systemic delivery of nonspecific COX and COX-2-selective inhibitors, but not a COX-1-selecti ve inhibitor. Given at systemic doses that block SP- and carrageenan-evoked hyperalgesia, COX-2, but not COX-1, inhibitors reduced spinal SP- evoked P GE(2) release. Thus, constitutive spinal COX-2, but not COX-1, is an import ant contributor to the acute antihyperalgesic effects of spinal as well as systemic COX-2 inhibitors.