Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation.
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.
Hsueh
Sheng-Fen
SF
Department of life Science, National Tsing Hua University, Hsinchu, Taiwan.
Lu
C-Y
CY
Chao
Chien-Shun
CS
Tan
P-H
PH
Huang
Y-W
YW
Hsieh
S-W
SW
Hsiao
H-T
HT
Chung
N-C
NC
Lin
S-H
SH
Huang
P-L
PL
Lyu
P-C
PC
Yang
L-C
LC
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
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