title: Anti-allodynic effect of mangiferin in neuropathic rats: Involvement of nitric oxide-cyclic GMP-ATP sensitive K+channels pathway and serotoninergic system.
abstract: The neurobiology of neuropathic pain is caused by injury in the central or peripheral nervous system. Recent evidence points out that mangiferin shows anti-nociceptive effect in inflammatory pain. However, its role in inflammatory and neuropathic pain and the possible mechanisms of action are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of mangiferin in rats with spinal nerve ligation (SNL). Furthermore, we sought to investigate the possible mechanisms of action that contribute to these effects. Mechanical allodynia to stimulation with the von Frey filaments was measured by the up and down method. Intrathecal administration of mangiferin prevented, in a dose-dependent fashion, SNL-induced mechanical allodynia. Mangiferin-induced anti-allodynia was prevented by the intrathecal administration of L-NAME (100μg/rat, non-selective nitric oxide synthase inhibitor), ODQ (10μg/rat, inhibitor of guanylate-cyclase) and glibenclamide (50μg/rat, channel blocker of ATP-sensitive K+channels). Moreover, methiothepin (30μg/rat, non-selective 5-HT receptor antagonist), WAY-100635 (6μg/rat, selective 5-HT1Areceptor antagonist), SB-224289 (5μg/rat, selective 5-HT1Breceptor antagonist), BRL-15572 (4μg/rat, selective 5-HT1Dreceptor antagonist) and SB-659551 (6μg/rat, selective 5-HT5Areceptor antagonist), but not naloxone (50μg/rat, non-selective opioid receptor antagonist), were able to prevent mangiferin-induced anti-allodynic effect. These data suggest that the anti-allodynic effect induced by mangiferin is mediated at least in part by the serotoninergic system, involving the activation of 5-HT1A/1B/1D/5Areceptors, as well as the nitric oxide-cyclic GMP-ATP-sensitive K+channels pathway, but not by the opioidergic system, in the SNL model of neuropathic pain in rats.
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, 04960 Mexico, D.F., Mexico.
authors.forename: Antonio Espinosa
authors.initials: AE
authors.lastname: de Los Monteros-Zuñiga
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, 04960 Mexico, D.F., Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Izquierdo
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, 04960 Mexico, D.F., Mexico.
authors.forename: Geovanna Nallely
authors.initials: GN
authors.lastname: Quiñonez-Bastidas
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 Mexico, D.F., Mexico.
authors.forename: Héctor Isaac
authors.initials: HI
authors.lastname: Rocha-González
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, 04960 Mexico, D.F., Mexico. Electronic address: bgodinez@correo.xoc.uam.mx.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Godínez-Chaparro
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D054086:KATP Channels / Q000502:physiology*; D008719:Methiothepin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy*; D009569:Nitric Oxide / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D010879:Piperazines; D010881:Piperidones; D011725:Pyridines; D011985:Receptors, Serotonin; C108518:SB 22489G; D013141:Spiro Compounds; D044004:Xanthones; C013592:mangiferin; D009569:Nitric Oxide; D009270:Naloxone; D008719:Methiothepin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester
keywords: Mangiferin; Neuropathic pain; Nitric oxide; Potassium channels; Serotonergic receptors