Developing a successful treatment strategy for
neuropathic pain has remained a challenge among researcher and clinicians. Various animal models have been employed to understand the pathogenic mechanism of
neuropathic pain in experimental animals. The present study was designed to explore the possible
nitric oxide mechanism in the protective effect of
melatonin against chronic constriction injury (CCI) of sciatic nerve in rats. Following chronic constriction injury, various behavioral tests (
thermal hyperalgesia, cold
allodynia) and biochemical parameters (lipid peroxidation,
reduced glutathione,
catalase, and
nitrite) were assessed in sciatic nerves. Drugs were administered for 21 consecutive days from the day of surgery. CCI significantly caused
thermal hyperalgesia, cold
allodynia and oxidative damage. Chronic administration of
melatonin (2.5 or 5 mg/kg, ip) significantly attenuated
hyperalgesia, cold
allodynia and oxidative damage in sciatic nerves as compared to CCI group. Further,
L-NAME (5 mg/kg) pretreatment with sub-effective dose of
melatonin (2.5 mg/kg, ip) significantly potentiated
melatonin's protective effect which was significant as compared to their individual effect per se. However,
L-arginine (100 mg/kg) pretreatment with
melatonin (2.5 mg/kg, ip) significantly reversed its protective effects. Results of the present study suggest the involvement of
nitric oxide pathway in the protective effect of
melatonin against CCI-induced behavioral and biochemical alterations in rats.