title: Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice.
abstract: The mechanism underlying the analgesic effect of clonidine, an alpha(2)-adrenoceptor agonist, remains uncertain. Activation of alpha(2)-adrenoceptor induces the release of nitric oxide (NO) from endothelial cells, which has led us to test the hypothesis that the observed antinociceptive effect induced by the systemic administration of clonidine depends on the NO-cGMP pathway. The possible involvement of an opioid link in the antinociceptive effect of clonidine was also evaluated. The antinociceptive effect induced by systemic administration (intravenous or intraperitoneal) of clonidine was evaluated using the rat paw formalin, mice tail-flick and writhing tests. Clonidine (3-120 microg/kg) induces a dose-dependent antinociceptive effect in the formalin, tail-flick and writhing tests. The antinociceptive effect of clonidine in a dose that had no sedative effect assessed by rota rod test, was significantly reduced by NO-synthase and guanylyl cyclase inhibition. The antinociceptive effect of morphine, but not clonidine, was inhibited by naloxone. Our current results suggest that the antinociceptive effect of systemic clonidine does not involve the opioid receptor and is modulated by the NO-cGMP pathway.
authors.affiliation: Departamento de Farmacologia, Instituto de Biologia, Centro Biomedico, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Rio de Janeiro 20551-030, Brazil. demoura@uerj.br
authors.forename: Roberto Soares
authors.initials: RS
authors.lastname: de Moura
authors.forename: Anna Amélia S
authors.initials: AA
authors.lastname: Rios
authors.forename: Edmar J A
authors.initials: EJ
authors.lastname: Santos
authors.forename: Ana Beatriz Amorim
authors.initials: AB
authors.lastname: Nascimento
authors.forename: Angela
authors.initials: A
authors.lastname: de Castro Resende
authors.forename: Miguel Lemos
authors.initials: ML
authors.lastname: Neto
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: de Oliveira
authors.forename: Antonio Cláudio
authors.initials: AC
authors.lastname: Mendes Ribeiro
authors.forename: Tania
authors.initials: T
authors.lastname: Tano
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D009569:Nitric Oxide; D006152:Cyclic GMP; D003000:Clonidine