Co-administration of ascorbic acid and α-tocopherol modifies ascorbic acid and attenuates p38, Akt, and TNF-α expression in spinal cord of rats with neuropathic pain

Abstract

p38 and Akt plays an important role in neuropathic pain. p38 appears to regulate the SVCT-2 expression, a specific transporter for ascorbic acid (an important antioxidant and neuromodulator). Vitamins C and E induce antinociception and appear to affect p38, Akt, and SVCT-2, but it is unknown their effect on these molecules in spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. So, we investigated the effect of vitamins C + E on the expression of p38, Akt, and transporter SVCT-2 and ascorbic acid content in the lumbosacral spinal cord of rats with CCI. TNF-α mRNA level was also determined. Placement of four loose chromic thread ligatures around the sciatic nerve produced CCI. Ascorbic acid (vitamin C 30 mg/kg/day) + α-tocopherol (vitamin E 15 mg/kg/day) or vehicle (saline containing 1% Tween 80) were administrated (intraperitoneally) daily after CCI for 3 or 10 days. At the end of these periods, lumbosacral spinal cord was dissected out and used for assays. The vitamins prevented the increase in phosphorylated p38 and phosphorylated Akt and the decrease in SVCT-2 expressions, which were found in vehicle-treated CCI rats at days 3 and 10. Akt expression was reduced only at day 10. Vitamins also prevented the increase in ascorbic acid content and TNF-α level, which was found in vehicle-treated CCI rats. The changes in p-p38, p-Akt, ascorbic acid, SVCT-2, and TNF-α may be contributing to antinociception induced by vitamins C + E in rats with CCI.