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 involved in the inflammatory response. Peripheral inflammation induced by intraplantar injection of carrageenan is associated with a marked increase in COX-2 mRNA and prostaglandins in the surrounding tissue and the accompanying oedema is sensitive to COX-2-selective drugs. In this study, 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 inhibitor DuP 697. Intraplantar injection of carrageenan caused a marked hyperalgesia at 4 h which was significantly attenuated by treatment with DuP 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 treatment. However, DuP 697 potentiated COX-2 mRNA induction, which indicates the existence of a potential regulatory mechanism to overcome COX-2 inhibition.
Hay
C
C
Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
de Belleroche
J
J
D000818:Animals; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008161:Lumbosacral Region; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D013314:Stress, Mechanical; D013876:Thiophenes / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013876:Thiophenes; C064874:DuP 697; D002351:Carrageenan; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases