Effect of L-NAME on Neuropathic Pain Developed after Peripheral Nerve Injury

Han, Sung Hee; Lee, Sang Chul; Kim, Yong Chul; Lim, Young Jin; Sung, Jae Sang

Abstract

BACKGROUND: Nitric oxide is known to play an important role in development of the neuropathic pain after peripheral nerve injury. However, it has not yet been investigated whether the role of nitric oxide differs in different modalities of neuropathic pain, such as mechanical, thermal, or cold. Neither has it been investigated whether nitric oxide has different roles in different stages of neuropathic pain, such as its development or maintenance.
METHODS
Neuropathic pain was induced by resection of the sciatic nerve branches. A nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), was injected intrathecally in one group, and around the resected nerve in the other. For half of each group, it was done before resection of the nerves, whereas it was done after the resection for the other half of each group. Responses to mechanical, thermal, and cold stimuli were observed for all of them. For another two groups of rats, L-NAME was administered intraperitoneally for two weeks before or after nerve resection. Influence of L-NAME on histologic change was investigated using both HE staining and immunohistochemcal staining.
RESULTS
Pain behavior was significantly attenuated or decreased for those who were treated with L-NAME before the nerve resection, either intrathecally or locally. Those who were treated with L-NAME after a nerve resection, there was no effect for the locally injected group and limited effect for the intrathecally injected group. Duration and intensity of pain behaviors differed with respect to pain modalities. Microscopic findings from HE staining showed that inflammatory reaction was significantly reduced in the pretreatment group, and the evidence of severe inflammation was seen in both the posttreatment group and the control group. I mmunohistochemical study showed no iNOS staining in the pretreatment group, whereas it showed staining in both the posttreatment group and the control group.
CONCLUSIONS
Nitric oxide plays an important role in the development of neuropathic pain, and it seems to work at both the spinal cord level and at the site of the injured nerve. However, its role in the injured nerve does not seem to be crucial in the maintenance of neuropathic pain. It is suggested that nitric oxide may have different mechanisms of action for different modalities of pain. Inflammatory reaction and iNOS at the site of nerve injury seem to play an important role in the development and/or maintenance of neuropathic pain.