Evidence for the involvement of the nitric oxide-cGMP pathway in the antinociception of morphine in the formalin test.
The effect of inhibition of nitric oxide synthesis and guanylate cyclase on the peripheral antinociceptive effect of morphine was assessed by using the formalin test in the rat. Saline, N(G)-monomethyl-L-arginine, a nitric oxide synthesis inhibitor (50 microg) and methylene blue, a guanylate cyclase inhibitor (500 microg), did not exhibit any antinociceptive activity. However, morphine (10 microg) produced a significant antinociceptive effect in phases 2a and 2b, which was reduced by pretreatment with either N(G)-monomethyl-L-arginine or methylene blue. These results suggest that the local administration of morphine induces antinociception by the activation of the L-arginine-nitric oxide-cGMP pathway.
Granados-Soto
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Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, DF, Mexico.
Rufino
M O
MO
Gomes Lopes
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LD
Ferreira
S H
SH
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D005557:Formaldehyde; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009020:Morphine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue