Selective inhibitors of cyclo-oxygenase-2 (COX-2) induce hypoalgesia in a XXXX paw model of inflammation.

@entity1 @entity13586 @entity12698 @entity1931 @entity5230 @entity4 @entity3009 @entity9774 @entity158 @entity35 @entity3352 @entity32912
1. It is well-established that inhibitors of cyclo-oxygenase (COX) and hence of @entity3009 (PG) biosynthesis reverse inflammatory @entity1931 and @entity4 in both @entity1 and animal models of @entity158 . 2. Paw @entity4 and @entity1931 in @entity35 were induced by injecting carrageenan (250 micro g paw(-1)) into a hindpaw. Both inflammatory responses were followed for 24 h after the injection, measuring @entity1931 by decreased @entity158 threshold in the paws and @entity4 by plethysmography. 3. Three selective inhibitors of cyclo-oxygenase-2 (COX-2), @entity12698 , @entity13586 and @entity32912 , given systemically in a range of doses, before the inflammatory stimulus, abolished carrageenan-induced @entity1931 with @entity4 . These inhibitors also induced hypoalgesia, increasing nociceptive thresholds in the inflamed paw above normal, non-inflamed levels. This hypoalgesia was lost at the higher doses of the selective inhibitors, although @entity1931 was still prevented. 4. In paws injected with saline only, @entity12698 , given at the dose inducing the maximum hypoalgesia after carrageenan, did not alter the nociceptive thresholds. 5. Two non-selective inhibitors of COX-2, @entity3352 and @entity5230 , abolished @entity1931 and reduced @entity4 but did not induce hypoalgesia. 6. @entity12698 given locally into the paw also abolished inflammatory @entity1931 and induced hypoalgesia without reducing @entity4 . 7. We conclude that hypoalgesia is expressed only over a critical range of COX-2 inhibition and that concomitant inhibition of @entity9774 prevents expression of hypoalgesia, although @entity1931 is still prevented. 8 Our results suggest a novel anti-nociceptive pathway mediating hypoalgesia, involving COX-2 selectively and having a clear peripheral component. This peripheral component can be further explored for therapeutic purposes.
