Dual effect of local application of nitric oxide donors in a model of incision pain in rats.

Abstract

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.

• Authors: Wiliam A Prado, Viviane F Schiavon, Fernando Q Cunha
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 441 Issue 1-2 Pg. 57-65 (Apr 19 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12007920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
• Diuretics, Osmotic
• Enzyme Inhibitors
• Nitric Oxide Donors
• Nitrites
• Ointments
• Oxadiazoles
• Quinoxalines
• S-nitro-N-acetylpenicillamine
• Guanylate Cyclase
• Penicillamine
• Isosorbide

Topics

• Animals
• Disease Models, Animal
• Diuretics, Osmotic (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Guanylate Cyclase (antagonists & inhibitors, metabolism)
• Hindlimb (surgery)
• Hyperalgesia (prevention & control)
• Isosorbide (pharmacology)
• Macrophages, Peritoneal (cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Donors (pharmacology)
• Nitrites (metabolism)
• Ointments
• Oxadiazoles (pharmacology)
• Pain Threshold (drug effects)
• Pain, Postoperative (physiopathology, prevention & control)
• Penicillamine (analogs & derivatives, pharmacology)
• Quinoxalines (pharmacology)
• Rats
• Rats, Wistar
• Time Factors