Vitamin C enhances the analgesic effect of gabapentin on rats with neuropathic pain

Aims: Gabapentin (Gap) relieves neuropathic pain, but it has several adverse effects as well. We aimed to investigate whether vitamin C (VitC) supplementation would reduce the effective dose of Gap for analgesia in rats with chronic constriction injury (CCI). Main methods: Rats were randomly assigned to Sham, CCI, VitC, Gap, and VitC + Gap treatment groups. CCI, involving the left sciatic nerve, was induced in all animals except the Sham group. VitC (500 mg/kg (body weight)), Gap (10, 30, or 100 mg/kg), or VitC (500 mg/kg) + Gap (10, 30, or 100 mg/kg) were injected intraperitoneally twice daily for a week from 7 days after sham or CCI surgery. Mechanical paw withdrawal threshold (PWT), thermal paw withdrawal latency (PWL) and malondialdehyde (MDA) content in serumor spinal cord tissues were all measured. The expression of sodium dependent vitamin C transporter 2 (SVCT2) and glucose transporter 3 (GLUT3) in dorsal root ganglion (DRG) were detected by quantitative real-time PCR, Western blot and immunohistochemistry. Key findings: No more than 30 mg/kg Gap could restore the decrease of PWT or PWL induced by CCI so long as combined with 500 mg/kg VitC. For mechanism study, we found that VitC supplementation would remarkedly ameliorate oxidative stress in peripheral blood, and possibly cause a positive feedback in VitC uptake of neurons in DRG by promoting SVCT2 expression. Significance: Vitamin C can enhance gabapentin's analgesic effect. And the underlying mechanism may be concerned with antioxidative responses which were more obvious in peripheral blood than in the neurons. (C) 2016 Elsevier Inc. All rights reserved.