CARRAGEENAN-INDUCED HYPERALGESIA IS ASSOCIATED WITH INCREASED CYCLO-OXYGENASE-2 EXPRESSION IN SPINAL-CORD

THE discovery of the inducible form of cyclo-oxygenase, known as cyclo -oxygenase-2 (COX-2), has provided insight into the mechanisms involve d in the inflammatory response. Peripheral inflammation induced by int raplantar injection of carrageenan is associated with a marked increas e in COX-2 mRNA and prostaglandins in the surrounding tissue and the a ccompanying oedema is sensitive to COX-2-selective drugs. In this stud y, we investigated whether COX-2 in spinal cord was similarly induced by carrageenan and whether the associated development of altered pain sensitivity, hyperalgesia was affected by the COX-2 selective inhibito r DuP 697. Intraplantar injection of carrageenan caused a marked hyper algesia at 4 h which was significantly attenuated by treatment with Du P 697 (10 mg kg(-1)). At the same time levels of COX-2 mRNA in lumbar spinal cord were significantly increased two-fold by carrageenan treat ment. However, DuP 697 potentiated COX-2 mRNA induction, which indicat es the existence of a potential regulatory mechanism to overcome COX-2 inhibition.