title: Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice.
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.
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Enderson D
authors.initials: ED
authors.lastname: de Oliveira
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Cristhine
authors.initials: C
authors.lastname: Schallenberger
authors.affiliation: 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.
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Böhmer
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Aécio C
authors.initials: AC
authors.lastname: Fagundes
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Michael
authors.initials: M
authors.lastname: Milman
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Marcos D P
authors.initials: MD
authors.lastname: Silva
authors.affiliation: 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.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Oses
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Lisiane O
authors.initials: LO
authors.lastname: Porciúncula
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Luís V
authors.initials: LV
authors.lastname: Portela
authors.affiliation: Department of Pharmacology, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Elisabetsky
authors.affiliation: Department of Biochemistry, Institute of Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.affiliation: 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.
authors.forename: André P
authors.initials: AP
authors.lastname: Schmidt
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D006147:Guanine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D007278:Injections, Spinal; D007288:Inosine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D051379:Mice; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D011687:Purines / Q000134:cerebrospinal fluid; D018047:Receptors, Purinergic P1 / Q000378:metabolism
chemical_list: D000700:Analgesics; D011687:Purines; D018047:Receptors, Purinergic P1; D007288:Inosine; D006147:Guanine; C030985:purine
keywords: Guanine; Inosine; Nociception; Pain; Purines; Spinal cord