Ascorbic acid eliminated pain-induced peripheral neuropathy by modulation of nitric oxide pathway in rats

Purpose Ascorbic acid (AA) diminishes superoxide and thereby prevents peroxynitrite formation from superoxide and nitric oxide (NO). As the neuropathic pain could be a consequence of a defect in antioxidant defenses and changes in reactive nitrogen species, the present study was designed to investigate the involvement of NO pathway in the analgesic effect of ascorbate in the chronic constriction injury (CCI) of the sciatic nerve model in rats. Methods Neuropathic pain induced by CCI of sciatic nerve. Sixty-four adult male rats were randomly set aside to experimental groups (control, vehicle, and treatment received AA, treatment received AA and l -arginine or l -NAME). Ascorbic acid (1, 5 mg/kg) or saline injected intraperitoneally 2 weeks after CCI. Paw withdrawal threshold and response rate were assessed by a radiant heat and acetone spray test 30 and 60 min after injection. To investigate the possible implication of NO on the analgesic effect of 5 mg/kg of AA on the second week after CCI, 60 min after injection of saline or AA, animals received an intraperitoneal injection of l -arginine (500 mg/kg), or l -NAME (20 mg/kg) and behavioral tests achieved 20 min after on. Blood samples were collected from animal groups 2 weeks after the onset of treatment for evaluation of the activities of antioxidant defense system factors such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), and catalase. At the same time, lipid hydroperoxide (LPO) as a prooxidant marker, and ascorbic acid concentration also determined in plasma. Results Single injection of 5 mg/kg but not 1 mg/kg of AA decreased pain symptoms in the second week after CCI ( P < 0.001, F = 3, F = 3.2). Injection of 5 mg/kg AA alleviated the nociceptive effect of l -arginine and enhanced the analgesic effect of l -NAME and pain threshold was significantly altered in these two groups comparing the animals which received normal saline instead of AA ( P < 0.001, P < 0.05, F = 2, F = 1.8, respectively). Ascorbic acid treatment (5 mg/kg) significantly improved oxidative damage as according to the decrease in the lipid peroxidation level ( P < 0.01, F = 5), increasing in glutathione, glutathione peroxidase, and superoxide dismutase levels ( P < 0.001, F = 11.25, F = 12.52, F = 5.65) and rising in catalase activity ( P < 0.001, F = 4.7) and ascorbic acid ( P < 0.001, F = 4.5) in plasma as compared with normal saline-treated rats. Conclusions Data of this study implied the implication of nitric oxide pathway in defending effect of ascorbic acid against CCI-induced behavioral and biochemical changes in rats.