title: Evidence for a central mechanism of action of S-(+)-ketoprofen.
abstract: It has been observed that some non-steroidal anti-inflammatory drugs (NSAIDs) may act through several mechanisms, in addition to central inhibition of prostaglandin synthesis. These other mechanisms include the L-arginine-nitric oxide (L-arginine-NO) pathway, as well as endogenous opiate and serotonergic mechanisms. Some of these mechanisms can explain the efficacy of NSAIDs in chronic pain conditions such as rheumatoid arthritis. The present study was designed to elucidate the involvement of the above pathways/mechanisms in the antinociceptive effect of S-(+)-ketoprofen at supraspinal and spinal levels. S-(+)-ketoprofen induced dose-dependent antinociception in the pain-induced functional impairment model in the rat. The antinociceptive effect of S-(+)-ketoprofen was not altered by i.t. or intracerebroventricula (i.c.v.) pre-treatment with L-arginine (29.6 microg/site) and L-nitro-arginine-monomethylester (L-NAME) (21.1 microg/site) and neither was the effect of S-(+)-ketoprofen modified by the opiate antagonist, naloxone (1 mg/kg, s.c.). In marked contrast, both i.c.v. administration of the 5-hydroxytryptamine (5-HT)(1)/5-HT(2)/5-HT(7) receptor antagonist, methiothepin (1.5 microg/site), and i.t. administration of the 5-HT(3)/5-HT(4) receptor antagonist, tropisetron (0.9 microg/site), significantly inhibited the S-(+)-ketoprofen-induced antinociceptive effect. These data suggest that the antinociceptive response to S-(+)-ketoprofen involves serotoninergic mechanisms via both supraspinal 5-HT(1)/5-HT(2)/5-HT(7) receptors and 5-HT(3) receptors located at spinal level. A role of the L-arginine-NO and opiate systems in S-(+)-ketoprofen-induced antinociception in the pain-induced functional impairment model in the rat model seems unlikely.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Col. Villa San Sebastián, C.P. 28045 Colima, Col., Mexico. idiazre@cgic.ucol.mx
authors.forename: María Irene
authors.initials: MI
authors.lastname: Díaz-Reval
authors.forename: Rosa
authors.initials: R
authors.lastname: Ventura-Martínez
authors.forename: Myrna
authors.initials: M
authors.lastname: Déciga-Campos
authors.forename: José A
authors.initials: JA
authors.lastname: Terrón
authors.forename: Francesc
authors.initials: F
authors.lastname: Cabré
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: López-Muñoz
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D007660:Ketoprofen / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
chemical_list: D000700:Analgesics; D011985:Receptors, Serotonin; D007660:Ketoprofen