Opioid modulation of the antinociceptive activity of L-arginine in mice Modulación opioide de la actividad antinociceptiva de L-arginina en ratones

Chanqueo L.; Yates L; Miranda, H. F.; Pinardi, G

Keywords: model, mouse, synthase, naloxone, experiment, naltrexone, receptor, oxide, methyl, dose, antinociception, article, arginine, antagonist, ester, blocking, test, controlled, animal, naltrindole, study, response, cyclic, nonhuman, gmp, nitric, ornithine, opiate, writhing, neuromodulation, n(g), nitroarginine, pharmacological, norbinaltorphimine


Objectives: Nitric oxide (NO) is an intercellular neuromodulator synthetized by NO synthetase (NOS). L-arginine (L-ARG) is converted to ornithine and NO by NOS and is involved in the L-ARG-NO pathway of nociceptive transmission and/or modulation in the CNS and in the periphery. In the present work, the antinociceptive activity of L-ARG was determined and the effects of non selective and selective opioid antagonists was evaluated. Material and methods: The dose-response curve for the antinociceptive effect of intraperitoneal (i.p.) L-ARG was determined in CF-1 mice, using the acetic acid writhing test. The dose-response curves were repeated after pretreatment with the following opioid receptor antagonists: Naloxone and naltrexone (non selective), naltrindole (? antagonist) y norbinaltorphimine (? antagonist). The antinociceptive activity of a single dose of L-ARG administered intrathecally (i.t.) and intracerebro-ventricularly (i.c.v.) was determined by the same algesiometric test. Results: L-ARG i.p. exhibited a dose-dependent antinociceptive activity, with an ED50 of 4,65 mg,kg-5 NOS inhibition significatively reduced the antinociceptive effect of L-ARG. The administration by the i.t. and i.c.v, routes of a dose approximately 45 times lower (0,16 and 0,15 mg.kg-1) produced a comparable antinociceptive effect. The pretreatment with all opioid receptor antagonists significantly displaced the dose-response curve for the antinociceptive activity of L-ARG to the right, indicating a pharmacologic antagonism. Conclusions: Systemically administered L-ARG, through NO formation and activation of cyclic GMP induce antinociception probably by a direct effect on peripheral nociceptors, additionally activating spinal and supraspinal antinociceptive mechanisms. The relation between systemic, intrathecal and intracerebroventricular equipotent doses suggests that a major part of the acción is exerted in the CNS. The synthesis and release of NO facilitates in some way the activation of opioid receptors at spinal and supraspinal levels and confirms the modulating action of NO in nociception. © 2000 Sociedad Española del Dolor.

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Título según SCOPUS: Opioid modulation of the antinociceptive activity of L-arginine in mice [Modulación opioide de la actividad antinociceptiva de L-arginina en ratones]
Volumen: 7
Número: 8
Editorial: Inspira Network Group, S.L
Fecha de publicación: 2000
Página de inicio: 520
Página final: 525
Idioma: Spanish
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0034495222&partnerID=q2rCbXpz