title: Possible involvement of nitric oxide modulatory mechanism in the protective effect of retigabine against spinal nerve ligation-induced neuropathic pain.
abstract: Decreasing the hyperexcitability of neurons through opening of voltage-gated potassium (Kv7) channels has been suggested as one of the protective mechanisms in the effective management of neuropathic pain. Reactive oxygen/nitrogen species are well implicated in the pathophysiology of neuropathic pain. Further, M current generated by opening of voltage-gated potassium channels (Kv7) 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/L6 spinal nerves resulted in alterations in various behavioral (as evident from marked increase in thermal and mechanical hyperalgesia, and allodynia) and biochemical (raised lipid peroxidation, nitrite, and depletion of GSH, SOD, and catalase) cascades as compared to sham treatment. Administration of retigabine (10 mg/kg) for 28 days attenuated these behavioral and biochemical cascades as compared to control rats. 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. The present study highlights the possible involvement of nitric oxide modulatory mechanism in the protective effect of retigabine against L5/L6 spinal nerve ligation-induced behavioral and biochemical alterations in rats.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, India.
authors.forename: Raghavender
authors.initials: R
authors.lastname: Pottabathini
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Archana
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Sukant
authors.initials: S
authors.lastname: Garg
mesh_terms: D000818:Animals; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries*
chemical_list: D002219:Carbamates; D018696:Neuroprotective Agents; D010655:Phenylenediamines; C101866:ezogabine; D009569:Nitric Oxide