Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice.
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.
de Moura
Roberto Soares
RS
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
Rios
Anna Amélia S
AA
Santos
Edmar J A
EJ
Nascimento
Ana Beatriz Amorim
AB
de Castro Resende
Angela
A
Neto
Miguel Lemos
ML
de Oliveira
Luiz Fernando
LF
Mendes Ribeiro
Antonio Cláudio
AC
Tano
Tania
T
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
D000700:Analgesics; D009569:Nitric Oxide; D006152:Cyclic GMP; D003000:Clonidine