Application of nitric oxide synthase inhibitor, Nω-nitro- l-arginine methyl ester, on injured nerve attenuates neuropathy-induced thermal hyperalgesia in rats

Abstract

This study tested the ability of a nitric oxide synthase inhibitor, N ω-nitro- l-arginine methyl ester ( l-NAME), to attenuate behavioral hyperalgesia in a rat model of neuropathic pain [Bennett, G.J. and Xie, Y.-K., Pain, 33 (1988) 87–107]. A mononeuropathy was produced by chronic constriction injury (CCI) of the sciatic nerve. Thermal hyperalgesia was assessed by a reduction of paw withdrawal latency to a noxious heat source. Following CCI, there was significant hyperalgesia in groups of rats treated with d-NAME ( n = 7), an inactive isomer of l-NAME, saline ( n = 7) or systemic l-NAME ( n = 10). In contrast, when l-NAME was applied directly and continuously to the site of CCI (5.0 μg/μl per h for up to 2 weeks) via an osmotic pump implanted at the time of the injury, no significant thermal hyperalgesia was observed ( n = 8). The results suggest the involvement of nitric oxide in the development and maintenance of thermal hyperalgesia in a rat model of neuropathy. The blockade of nitric oxide production at the site of injury may provide a new approach for treatment of neuropathic pain.