The symptoms of neuropathic pain are often intractable because they are poorly relieved by conventional analgesics. This therapeutic area remains one of the least satisfactorily managed by current drugs. Effective therapy for this type of pain is lacking, and the underlying mechanisms are poorly understood. The present study was undertaken to determine the effect of sciatic nerve ligation on inducing neuropathic pain and to understand the mechanisms involved, and the effect of, an L-nitro-arginine methyl ester (L-NAME)/dextromethorphan combination therapy on reducing neuropathic pain. According to our results, L-NAME and dextromethorphan showed analgesic properties, but only 100 mg/kg L-NAME had an additive effect on the analgesic effects of dextromethorphan. Our observations support the idea that N-methyl-D-aspartate/nitric oxide pathways play an important role in the development of such sciatic nerve ligated-evoked pathological pain conditions, thus this combination therapy could be used instead of conventional treatment.
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