Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice

Pharmacology, Biochemistry, and Behavior
Roberto Soares de MouraTania Tano

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.

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Citations

Oct 20, 2010·Basic & Clinical Pharmacology & Toxicology·Enoch Kumar PerimalMohd Roslan Sulaiman
Aug 29, 2012·Fundamental & Clinical Pharmacology·Rafael A S RangelMarcos A Lessa
Jul 26, 2005·Peptides·Richard J Bodnar, Gad E Klein
Jan 25, 2017·BMC Complementary and Alternative Medicine·Md Abdul MannanMd Farhad Hossen Khan

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