Dual effect of local application of nitric oxide donors in a model of incision pain in rats.
The effects of local application of a cream containing nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine (SNAP) or isosorbide dinitrate were studied in a rat model of incision pain. An incision was made in the plantar aspect of a hind paw and the cream was applied inside the surgical wound. SNAP (1-10%) or isosorbide (2.5-5%) reduced the incision allodynia as measured with von Frey filaments. Higher concentrations produced a smaller or no effect, but SNAP (30%) intensified the allodynia. Allodynia was also intensified by SNAP (5% or 30%) in rats pretreated with intraplantar 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 4 microg), a guanylate cyclase inhibitor. The effect of isosorbide (5%) was prevented by ODQ. The cream containing SNAP released 10- to 20-fold more nitrite than did isosorbide from a macrophage culture. We conclude that local application of drugs generating a low NO concentration reduces incision pain through activation of guanylate cyclase. Drugs generating high NO concentrations, however, intensify pain via a guanylate cyclase-independent mechanism.
Prado
Wiliam A
WA
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto-USP, Av. Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, São Paolo, Brazil. waprado@fmrp.usp.br
Schiavon
Viviane F
VF
Cunha
Fernando Q
FQ
D000818:Animals; D004195:Disease Models, Animal; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006614:Hindlimb / Q000601:surgery; D006930:Hyperalgesia / Q000517:prevention & control; D007547:Isosorbide / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D009824:Ointments; D010069:Oxadiazoles / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004234:Diuretics, Osmotic; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009573:Nitrites; D009824:Ointments; D010069:Oxadiazoles; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D006162:Guanylate Cyclase; D010396:Penicillamine; D007547:Isosorbide