Decreasing the hyper excitability of neurons through opening of voltage-gated potassium (Kv7, also termed as KCNQ) channels has been suggested as one of the protective mechanisms in the effective management of neuropathic pain. Reactive oxygen/nitrogen species and inflammatory pathways are well implicated in the pathophysiology of neuropathic pain. Further, M current generated by opening of KCNQ channels has been modulated by reactive oxygen/nitrogen species.

The present study has been designed to elucidate the nitric oxide modulatory mechanism in the protective effect of retigabine against spinal nerve ligation induced neuropathic pain in rats.

Ligation of L5 and L6 spinal nerves resulted alterations in various behavioral (as evident from marked increase in thermal and mechanical hyperalgesia and allodynia), biochemical (raised lipid peroxidation, nitrite, & depletion of GSH, SOD, catalase) and inflammatory parameters (raised TNF-alpha) as compared to naive treatment.

Administration of retigabine (10 mg/kg) for 28 days attenuated these behavioral, biochemical and inflammatory cascades as compared to control. Further, L-arginine (100 mg/kg) pretreatment with retigabine (5 mg/kg) significantly reversed the protective effect of retigabine in spinal nerve ligated rats. However, L-NAME (10 mg/kg) pretreatment with retigabine (5 mg/kg) significantly potentiated their protective effects which were significant as compared to their effect per se respectively.

Present study highlights the involvement of nitric oxide mechanism in the protective effect of retigabine against L5/L6 spinal nerve ligation induced behavioral and biochemical alterations in rats.