Evidence for a central mechanism of action of S-(+)-ketoprofen

María Irene Díaz-Reval, Rosa Ventura-Martínez, Myrna Déciga-Campos, José A. Terrón, Francesc Cabré, Francisco Javier López-Muñoz

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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 μg/site) and L-nitro-arginine- monomethylester (L-NAME) (21.1 μg/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-HT2/5-HT7 receptor antagonist, methiothepin (1.5 μg/site), and i.t. administration of the 5-HT 3/5-HT4 receptor antagonist, tropisetron (0.9 μg/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-HT1/5- HT2/5-HT7 receptors and 5-HT3 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.

Original languageEnglish
Pages (from-to)241-248
Number of pages8
JournalEuropean Journal of Pharmacology
Volume483
Issue number2-3
DOIs
StatePublished - 12 Jan 2004
Externally publishedYes

Keywords

  • 5-HT receptor antagonist
  • Antinociception
  • Methiothepin
  • Tropisetron

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