Involvement of peripheral cyclooxygenase-1 and cyclooxygenase-2 in inflammatory pain.
Pain-induced functional impairment in the rat (PIFIR) is a model of inflammatory and arthritic pain similar to that of clinical gout. Nociception is induced by the intra-articular injection of uric acid into the right hind limb, inducing its dysfunction. Animals then receive analgesic drugs and the recovery of functionality over time is assessed as an expression of antinociception. We have examined the role of peripheral prostaglandins synthesized by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in inflammatory pain using the PIFIR model. Rofecoxib (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor) both produced dose-dependent effects. When the inhibitors were administered before uric acid, they showed similar potency, but the antinociceptive efficacy of SC-560 was lower than rofecoxib; the best antinociceptive effects were obtained with the dose of 100 microg/articulation of each inhibitor (pre-treatment). In post-treatment (inhibitors administered after the uric acid), rofecoxib showed the least antinociceptive effect and SC-560 was more potent than rofecoxib. The inhibition of both COX-1 and COX-2 produced a more profound analgesic effect than the inhibition of either COX-1 or COX-2 alone. The present data support the idea that both COX isoforms contribute to the development and maintenance of local inflammatory nociception. Thus, it could be expected that inhibition of both COX-1 and COX-2 is required for non-steroidal anti-inflammatory drugs (NSAID)-induced antinociception in the rat. These findings suggest that the therapeutic effects of NSAIDs may involve, at least in part, inhibition of COX-1 and COX-2.
Martínez
Rosa Ventura
RV
Departamento de Farmacobiología, CINVESTAV-IPN, México, DF, México.
Reval
MaIreneDíaz
M
Campos
Myrna Déciga
MD
Terrón
José Antonio
JA
Domínguez
RamírezAdrianaM
R
López-Muñoz
Francisco J
FJ
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007783:Lactones / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011453:Prostaglandins / Q000096:biosynthesis; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones; D014527:Uric Acid / Q000633:toxicity
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011453:Prostaglandins; D011720:Pyrazoles; C115461:SC 560; D013450:Sulfones; C116926:rofecoxib; D014527:Uric Acid