Local nitric oxide synthase activity in a model of neuropathic pain.
A local inflammatory reaction may play an important role in the development of neuropathic pain following peripheral nerve injury. One important participant in the inflammatory response of injured peripheral nerve may be nitric oxide (NO). In this work, we examined physiological and morphological evidence for nitric oxide synthase (NOS) activation in the chronic constriction injury model of neuropathic pain in rats. Physiological evidence of local NO action was provided by studying NO-mediated changes in local blood flow associated with the injury site. Immunohistochemistry was used to localize isoforms of NOS that might generate NO. Sciatic nerve injury associated with behavioural evidence of neuropathic pain had substantial rises in local blood flow. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), but not NG-nitro-D-arginine methyl ester (D-NAME), reversed the hyperaemia in a dose-dependent fashion proximal to the constriction at 48 h and distally at 14 days post-operation when applied systemically or topically. Aminoguanidine, a NOS inhibitor with relatively greater selectivity for the inducible NOS (iNOS) isoform, reversed nerve hyperaemia distal to the constriction only at 14 days. NOS-like immunoreactivity of the neuronal and endothelial isoforms was identified just proximal to the constriction at 48 h. iNOS-like immunoreactivity was observed at 7 and 14 days at the constriction and distal sites, respectively. This work provides evidence for local NOS expression and NO action in the chronic constriction injury model of neuropathic pain. NO has local physiological actions that include vasodilatation of microvessels and that may be important in the development of pain sensitivity.
Levy
D
D
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Zochodne
D W
DW
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008657:Metabolic Clearance Rate; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009437:Neuralgia / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012039:Regional Blood Flow; D012584:Sciatic Nerve / Q000293:injuries
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester