Modulación opioide de la actividad antinociceptiva de L-arginina en ratones

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

Resultado de la investigación: Article

Resumen

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 (δ antagonist) y norbinaltorphimine (κ 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 ED 50 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.

Idioma originalSpanish
Páginas (desde-hasta)520-525
Número de páginas6
PublicaciónRevista de la Sociedad Espanola del Dolor
Volumen7
N.º8
EstadoPublished - 2000

Huella dactilar

Opioid Analgesics
Arginine
Nitric Oxide
Narcotic Antagonists
naltrindole
Nitric Oxide Synthase
Nociceptors
Naltrexone
Ornithine
Nociception
Cyclic GMP
Opioid Receptors
Ligases
Naloxone
Acetic Acid
Neurotransmitter Agents

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Citar esto

Chanqueo, L., Yates, L., Miranda, H. F., & Pinardi, G. (2000). Modulación opioide de la actividad antinociceptiva de L-arginina en ratones. Revista de la Sociedad Espanola del Dolor, 7(8), 520-525.
Chanqueo, L. ; Yates, L. ; Miranda, H. F. ; Pinardi, G. / Modulación opioide de la actividad antinociceptiva de L-arginina en ratones. En: Revista de la Sociedad Espanola del Dolor. 2000 ; Vol. 7, N.º 8. pp. 520-525.
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abstract = "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 (δ antagonist) y norbinaltorphimine (κ 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 ED 50 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 acci{\'o}n 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.",
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Chanqueo, L, Yates, L, Miranda, HF & Pinardi, G 2000, 'Modulación opioide de la actividad antinociceptiva de L-arginina en ratones', Revista de la Sociedad Espanola del Dolor, vol. 7, n.º 8, pp. 520-525.

Modulación opioide de la actividad antinociceptiva de L-arginina en ratones. / Chanqueo, L.; Yates, L.; Miranda, H. F.; Pinardi, G.

En: Revista de la Sociedad Espanola del Dolor, Vol. 7, N.º 8, 2000, p. 520-525.

Resultado de la investigación: Article

TY - JOUR

T1 - Modulación opioide de la actividad antinociceptiva de L-arginina en ratones

AU - Chanqueo, L.

AU - Yates, L.

AU - Miranda, H. F.

AU - Pinardi, G.

PY - 2000

Y1 - 2000

N2 - 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 (δ antagonist) y norbinaltorphimine (κ 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 ED 50 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.

AB - 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 (δ antagonist) y norbinaltorphimine (κ 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 ED 50 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.

KW - Antinociception

KW - L-arginine

KW - Nitric oxide

KW - Opioid antagonists

KW - Writhing test

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M3 - Article

AN - SCOPUS:0034495222

VL - 7

SP - 520

EP - 525

JO - Revista de la Sociedad Espanola del Dolor

JF - Revista de la Sociedad Espanola del Dolor

SN - 1134-8046

IS - 8

ER -