LOCAL NITRIC-OXIDE SYNTHASE ACTIVITY IN A MODEL OF NEUROPATHIC PAIN

A local inflammatory reaction may play an important role in the develo pment of neuropathic pain following peripheral nerve injury. One impor tant participant in the inflammatory response of injured peripheral ne rve 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 g enerate NO. Sciatic nerve injury associated with behavioural evidence of neuropathic pain had substantial rises in local blood flow. The NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME), but not N-G-nit ro-D-arginine methyl ester (D-NAME), reversed the hyperaemia in a dose -dependent fashion proximal to the constriction at 48 h and distally a t 14 days post-operation when applied systemically or topically, Amino guanidine, 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 neuron al and endothelial isoforms was identified just proximal to the constr iction at 48 h. iNOS-like immunoreactivity was observed at 7 and 14 da ys at the constriction and distal sites, respectively. This work provi des evidence for local NOS expression and NO action in the chronic con striction injury model of neuropathic pain. NO has local physiological actions that include vasodilatation of microvessels and that may be i mportant in the development of pain sensitivity.