title: Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation.
abstract: Several lines of evidence have accumulated that release of excitatory amino acids, nitric oxide and prostaglandin E2 (PGE2) play a critical role in the development of peripheral tactile and thermal hypersensitivity in chronic inflammatory pain models. Synthesis of PGE2 is controlled by cyclooxygenase (COX), either the COX-1 or COX-2 isoform. COX-2 plays a central role in the inflammatory reactions. The relationship between central sensitization of a complete Freund's adjuvant (CFA) induced inflammation and expressions of COX-2 were assessed in a rat model of CFA injection induced inflammation. Moreover, the time course of analgesia and spinal COX-2 expression following intrathecal (IT) injection with a nonspecific COX inhibitor (ketorolac) and COX-2 inhibitor (celecoxib) were determined using Western blot and immunohistochemistry. COX-2 protein was slightly increased in the lumbosacral spinal cord at 24 h following subcutaneous injection of CFA in the plantar surface of the left hindpaw (p > 0.05). COX-1 was not detected in normal and CFA injection rats. Surprisingly, IT ketorolac or celecoxib significantly increased spinal COX-2 levels at 1 h post-IT injection (p < 0.05) both in inflamed and non-inflamed rats. Then, spinal COX-2 levels declined at 3 and 6 h post-IT injection. These results provide strong in vivo evidence that COX-2 activity but not level may play a central role in the Freund's adjuvant-induced inflammation. However, spinal COX-2 level was upregulated following IT ketorolac and celecoxib injection. These data implies that suppression of PGE2 activity may induce the expression of spinal COX-2 in Freund's adjuvant-induced pain model. Our study concludes that IT administration of COX-2 inhibitor or nonspecific COX inhibitor is associated with significant short-term increase in spinal COX-2 expression.
authors.affiliation: Department of life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Sheng-Fen
authors.initials: SF
authors.lastname: Hsueh
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lu
authors.forename: Chien-Shun
authors.initials: CS
authors.lastname: Chao
authors.forename: P-H
authors.initials: PH
authors.lastname: Tan
authors.forename: Y-W
authors.initials: YW
authors.lastname: Huang
authors.forename: S-W
authors.initials: SW
authors.lastname: Hsieh
authors.forename: H-T
authors.initials: HT
authors.lastname: Hsiao
authors.forename: N-C
authors.initials: NC
authors.lastname: Chung
authors.forename: S-H
authors.initials: SH
authors.lastname: Lin
authors.forename: P-L
authors.initials: PL
authors.lastname: Huang
authors.forename: P-C
authors.initials: PC
authors.lastname: Lyu
authors.forename: L-C
authors.initials: LC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005620:Freund's Adjuvant / Q000276:immunology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology*; D007278:Injections, Spinal; D007527:Isoenzymes / Q000378:metabolism*; D020910:Ketorolac / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D020910:Ketorolac