2. Academic Validation
  3. Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice

Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice

  • Eur J Pharmacol. 2016 Feb 5:772:71-82. doi: 10.1016/j.ejphar.2015.12.034.
Enderson D de Oliveira 1,  Cristhine Schallenberger 1,  Ana Elisa Böhmer 2,  Gisele Hansel 1,  Aécio C Fagundes 1,  Michael Milman 1,  Marcos D P Silva 1,  Jean P Oses 3,  Lisiane O Porciúncula 1,  Luís V Portela 1,  Elaine Elisabetsky 4,  Diogo O Souza 1,  André P Schmidt 5
Affiliations

Affiliations

  • 1 Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
  • 2 Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
  • 3 Programa de Pós-graduação em Saúde e Comportamento, Centro de Ciências da Vida e da Saúde e Hospital Universitário São Francisco de Paula, Universidade Católica de Pelotas, Pelotas, RS, Brazil.
  • 4 Department of Pharmacology, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
  • 5 Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Anaesthesia and Perioperative Medicine, Hospital de Clínicas de Porto Alegre (HCPA), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Division of Anaesthesia, Department of Surgery, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil. Electronic address: aschmidt@ufrgs.br.
PMID: 26712379 DOI: 10.1016/j.ejphar.2015.12.034
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 (30mN NaOH), inosine or guanine (up to 600nmol) 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 (200nmol) 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

Guanine; Inosine; Nociception; Pain; Purines; Spinal cord.

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