This Article Résumé de cet Article Full Text Full Text (PDF) Submit a scholarly reply Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Doursout, M.-F. Articles by Chelly, J. E. Search for Related Content PubMed PubMed Citation Articles by Doursout, M.-F. Articles by Chelly, J. E.

NOS inhibitors exhibit antinociceptive properties in the rat formalin test

[Les inhibiteurs de NOS affichent des propriétés antinociceptives au test de formaline chez des rats]

From the Department of Anesthesiology, The University of Texas Medical School at Houston, Houston, Texas, USA.

Address correspondence to: Dr. Jacques E. Chelly, Department of Anethesiology, University of Pittsburgh School of Medicine, 3550 Terrace Street, A-1305 Scaife Hall, Pittsburgh, Pennsylvania 15261, USA. Phone: 412-648-9560; Fax: 412-648-1887; E-mail: chelje{at}anes.upmc.edu

Purpose: To assess the systemic and nociceptive effects of nitric oxide synthase (NOS) inhibitors in the modulation of acute pain in rats subjected to the formalin test.

Methods: Formalin 5% was injected in the hind paw in the presence and absence of NOS inhibitors (e.g., 7-nitro indazole, N-nitro-L-arginine and aminoguanidine). Catheters were chronically implanted to continuously record mean arterial blood pressure (MAP) and heart rate (HR). MAP, HR and paw lifting time were recorded at control and every five minutes for 35 min following formalin and NOS inhibitors.

Results: Formalin injected into the rat hind paw induced a biphasic nociceptive behaviour: an initial acute phase (phase 1: during zero to five minutes after the formalin injection) followed by a prolonged tonic response (phase 2: beginning about ten minutes after the formalin injection). Aminoguanidine, an inhibitor of the inducible NOS and 7-nitro indazole, an inhibitor of the neuronal NOS, did not affect phase 1, whereas N-nitro-L-arginine, a non-selective NOS inhibitor decreased it (49%). All three NOS inhibitors diminished nociceptive behaviours during phase 2. L-arginine reversed antinociceptive effects of N-nitro-L-arginine in phase 1 and in phase 2. Pressor effects induced by formalin in phase 1 were abolished following all three NOS inhibitors. During phase 2, formalin-induced pressor effects remained unaffected by N-nitro-L-arginine and aminoguanidine but were inhibited by 7-nitro indazole.

Conclusion: Our data demonstrate that NO is predominantly generated by vascular endothelial NOS in phase 1 and phase 2, whereas the neuronal NOS and the inducible NOS exhibit antinociceptive effects through a non-NO related pathway in phases 1 and 2 in rats subjected to the formalin test.