Intrathecal administration of nonsteroidal anti-inflammatory drugs in the rat blocks the
thermal hyperalgesia induced by tissue injury, which suggests a role for spinal
cyclooxygenase (COX) products in this facilitated state. Two
isozymes of the COX
enzyme have been reported, COX-1 and COX-2, but the agents thus far examined are not
isozyme selective. We examined the effects of intrathecally (i.t.) or systemically (i.p.) administered S(+)-
ibuprofen (a nonselective COX inhibitor) or 1-[(4-methysulfonyl)phenyl]-3-tri-fluoromethyl-5-(4-fluorophenyl)
pyrazole (
SC58125; a COX-2 selective 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 blocked in a dose-dependent manner by S(+)-
ibuprofen or
SC58125 administered i.t. or i.p. before
carrageenan treatment. 2) Intraperitoneal, but not i.t., administration of either inhibitor after the establishment of
hyperalgesia (170 min after
carrageenan injection) reversed
thermal hyperalgesia in a dose-dependent manner. Thus, the initial component of
thermal hyperalgesia after tissue injury was blocked by systemic or spinal administration of both COX inhibitors, whereas established
hyperalgesia was reversed only by systemic inhibitors. This study demonstrates that at least spinal COX-2, if not both COX-1 and COX-2, are necessary 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 with tissue injury and
inflammation.