The molecular mechanism of central analgesia induced by morphine or carbachol and the L-arginine-nitric oxide-cGMP pathway.
The role of the L-arginine-NO-cGMP pathway in morphine-induced central analgesia was investigated in two nociceptive tests: PGE2-induced hind paw hyperalgesia and tail-flick. The central analgesic effect of morphine was potentiated by MY5445, a specific cGMP phosphodiesterase inhibitor. I.c.v. injections of morphine or carbachol caused dose-dependent analgesia, which was prevented by methylene blue, an inhibitor of guanylate cyclase. The NO synthase inhibitor, N-iminoethyl-L-ornithine, prevented carbachol-induced analgesia, but did not affect morphine-induced analgesia. Our results suggest that activation of cGMP may underlies analgesia induced by morphine and carbachol. The activation of guanylate cyclase by carbachol seems to depend on the L-arginine-NO pathway, but that caused by morphine remains to be further characterized.
Duarte
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Faculty of Medicine, USP, Ribeirão Preto, Brazil.
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D000698:Analgesia; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D006152:Cyclic GMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D010793:Phthalazines; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; C002385:linsidomine; D009020:Morphine; D002217:Carbachol; D001120:Arginine; D008981:Molsidomine; D009952:Ornithine; C052490:MY 5445; D006152:Cyclic GMP; D015232:Dinoprostone