EFFECT OF COX-1 AND COX-2 INHIBITION ON INDUCTION AND MAINTENANCE OF CARRAGEENAN-EVOKED THERMAL HYPERALGESIA IN RATS

Intrathecal administration of nonsteroidal anti-inflammatory drugs in the rat blocks the thermal hyperalgesia induced by tissue injury, whic h suggests a role for spinal cyclooxygenase (COX) products in this fac ilitated state. Two isozymes of the COX enzyme have been reported, COX -1 and COX-2, but the agents thus far examined are not isozyme selecti ve. We examined the effects of intrathecally (i.t.) or systemically (i .p.) administered S(+)-ibuprofen (a nonselective COX inhibitor) or nyl ]-3-tri-fluoromethyl-5-(4-fluorophenyl)pyrazole (SC58125; a COX-2 sele ctive inhibitor) on carrageenan-induced thermal hyperalgesia (reduced hindpaw-withdrawal latency). The following observations were made: 1) Thermal hyperalgesia otherwise observed during the first 170 min was b locked in a dose-dependent manner by S(+)-ibuprofen or SC58125 adminis tered i.t. or i.p. before carrageenan treatment. 2) Intraperitoneal, b ut not i.t., administration of either inhibitor after the establishmen t of hyperalgesia (170 min after carrageenan injection) reversed therm al hyperalgesia in a dose-dependent manner. Thus, the initial componen t of thermal hyperalgesia after tissue injury was blocked by systemic or spinal administration of both COX inhibitors, whereas established h yperalgesia was reversed only by systemic inhibitors. This study demon strates that at least spinal COX-2, if not both COX-1 and COX-2, are n ecessary for the initiation of thermal hyperalgesia, whereas nonspinal sources of prostanoids (synthesized by COX-2 and perhaps also COX-1) are important for the maintenance of thermal hyperalgesia associated w ith tissue injury and inflammation.