Activation of the arginine-nitric oxide pathway in primary sensory neurons contributes to dipyrone-induced spinal and peripheral analgesia.
The objective of this study was to investigate the site of action of dipyrone in rat paw prostaglandin-induced hyperalgesia. The intracerebroventricular (i.c.v.) injection of dipyrone had no effect on the hyperalgesic response to prostaglandins. In contrast, intraplantar (i.pl.) and intrathecal (i.t.) injections produced dose-dependent analgesic effects. The analgesia observed following the intraperitoneal (i.p.), i.t., i.pl. or combined i.t. and i.pl. administration of dipyrone was abolished by pretreating the paws with L-NMMA (a nitric oxide synthase inhibitor) or methylene blue (MB, an inhibitor of soluble guanylate cyclase). These results support the suggestion that dipyrone-mediated antinociception results from a combined spinal and peripheral effect in the primary peripheral sensory neuron via stimulation of the arginine/cGMP pathway.
Lorenzetti
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Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, USP, Ribeirão Preto, São Paulo SP, Brazil.
Ferreira
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D000704:Analysis of Variance; D000775:Anesthesia, Spinal; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism; D015232:Dinoprostone / Q000008:administration & dosage / Q000633:toxicity*; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000633:toxicity; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000633:toxicity
D000892:Anti-Infective Agents, Urinary; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004177:Dipyrone; D001120:Arginine; D015232:Dinoprostone; D008751:Methylene Blue