Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation

• Published in: Brain research. Molecular brain research. 2004-06, Vol.125 (1), p.113-119
• Main Authors: Hsueh, Sheng-Fen, Lu, C.-Y, Chao, Chien-Shun, Tan, P.-H, Huang, Y.-W, Hsieh, S.-W, Hsiao, H.-T, Chung, N.-C, Lin, S.-H, Huang, P.-L, Lyu, P.-C, Yang, L.-C
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Celecoxib; Complete Freund's adjuvant; Cyclooxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Excitatory amino acids; Freund's Adjuvant - immunology; Fundamental and applied biological sciences. Psychology; Hot Temperature; Hyperalgesia - metabolism; Inflammation - enzymology; Injections, Spinal; Intrathecal; Isoenzymes - metabolism; Ketorolac - metabolism; Ketorolac - pharmacology; Male; Pain - drug therapy; Pain - metabolism; Pain Measurement; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins; Pyrazoles; Random Allocation; Rats; Rats, Sprague-Dawley; Spinal cord; Spinal Cord - cytology; Spinal Cord - enzymology; Spinal Cord - pathology; Sulfonamides - metabolism; Sulfonamides - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2004.03.016

Several lines of evidence have accumulated that release of excitatory amino acids, nitric oxide and prostaglandin E 2 (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