TY - JOUR
T1 - Evidence for a central mechanism of action of S-(+)-ketoprofen
AU - Díaz-Reval, María Irene
AU - Ventura-Martínez, Rosa
AU - Déciga-Campos, Myrna
AU - Terrón, José A.
AU - Cabré, Francesc
AU - López-Muñoz, Francisco Javier
PY - 2004/1/12
Y1 - 2004/1/12
N2 - 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.
AB - 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.
KW - 5-HT receptor antagonist
KW - Antinociception
KW - Methiothepin
KW - Tropisetron
UR - http://www.scopus.com/inward/record.url?scp=0346687642&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2003.10.036
DO - 10.1016/j.ejphar.2003.10.036
M3 - Artículo
SN - 0014-2999
VL - 483
SP - 241
EP - 248
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -