Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5826802 | European Journal of Pharmacology | 2016 | 42 Pages |
Abstract
It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that guanine-based purines may produce some antinociceptive effects against chemical and thermal pain in mice. The present study was designed to investigate the antinociceptive effects of intrathecal (i.t.) administration of inosine or guanine in mice. Additionally, investigation into the mechanisms of action of these purines, their general toxicity and measurements of CSF purine levels were performed. Animals received an i.t. injection of vehicle (30Â mN NaOH), inosine or guanine (up to 600Â nmol) and submitted to several pain models and behavioural paradigms. Guanine and inosine produced dose-dependent antinociceptive effects in the tail-flick, hot-plate, intraplantar (i.pl.) glutamate, i.pl. capsaicin and acetic acid pain models. Additionally, i.t. inosine inhibited the biting behaviour induced by spinal injection of capsaicin and i.t. guanine reduced the biting behaviour induced by spinal injection of glutamate or AMPA. Intrathecal administration of inosine (200Â nmol) induced an approximately 115-fold increase on CSF inosine levels. This study provides new evidence on the mechanism of action of extracellular guanine and inosine presenting antinociceptive effects following spinal administration. These effects seem to be related, at least partially, to the modulation of A1 adenosine receptors.
Keywords
ZM241385TRPV1ADPNMDAN-methyl-d-aspartatePNPDPCPXAMPAGMPIMPA2AHGPRTInosineAMPPurinesAOPCPGTPMPESCH582618-PT(±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid8-Cyclopentyl-1,3-dipropylxanthineDMSOAdenosine TriphosphateATPadenosine diphosphateadenosine monophosphatei.t.α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidintrathecaltrans-ACPDGDPMaximum possible effectPainCNSDimethyl sulfoxidecentral nervous systemSpinal cordnociceptionCSFCerebrospinal fluidInosine monophosphatehypoxanthine-guanine phosphoribosyl transferasePurine nucleoside phosphorylasehigh-performance liquid chromatographyHPLCGuanosine monophosphateGuanosine triphosphateguanosine diphosphateGuanine
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Authors
Enderson D. de Oliveira, Cristhine Schallenberger, Ana Elisa Böhmer, Gisele Hansel, Aécio C. Fagundes, Michael Milman, Marcos D.P. Silva, Jean P. Oses, Lisiane O. Porciúncula, LuÃs V. Portela, Elaine Elisabetsky, Diogo O. Souza, André P. Schmidt,