The role of cyclooxygenase-1 and -2 in the rat formalin test.
Prostaglandins are thought to play an important role in nociceptive transmission at peripheral sites and in the spinal cord. Prostaglandins are produced by cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid. Two forms of COX have been identified: COX-1, which is constitutively expressed, and COX-2, which is an inducible enzyme. To define the role of COX-1 in nociceptive transmission, we examined the effect of oral and intrathecal administration of 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560), a selective COX-1 inhibitor, on the rat formalin test and compared the effect of SC-560 with that of celecoxib, a COX-2 selective inhibitor, and indomethacin, a nonselective COX-1 and COX-2 inhibitor, on the rat formalin test. Oral and intrathecal administration of SC-560 had no effect on the agitation behavior in the rat formalin test. Oral and intrathecal administration of celecoxib and indomethacin depressed agitation behavior during the rat formalin test. These data suggest that prostaglandins synthesized by COX-1 are not involved in nociceptive transmission during the rat formalin test but that COX-2 does play an important role in the rat formalin test.


CONCLUSIONS
Our data suggest that a COX-2 selective inhibitor, but not a COX-1 selective inhibitor, may produce a good analgesic effect on the inflammatory pain state in a clinical situation.
Yamamoto
Tatsuo
T
Department of Anesthesiology, Chiba University Hospital, Chiba, Japan. yamatat@med.m.chiba-u.ac.jp
Nozaki-Taguchi
Natsuko
N
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005557:Formaldehyde; D007213:Indomethacin / Q000494:pharmacology; D007278:Injections, Spinal; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D009431:Neural Conduction / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D005557:Formaldehyde; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D000068579:Celecoxib; D007213:Indomethacin