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
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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.
KeywordsPhosphorylated p38 Phosphorylated Akt Chronic constriction injury Sciatic nerve
Protein kinase B
Analysis of variance
Chronic constriction injury
Ethics Committee of the Universidade Federal do Rio Grande do Sul
Mitogen-activated protein kinases
Protein kinase B in phosphorylated form
p38 in phosphorylated form
Sodium dodecyl sulfate–polyacrylamide gel electrophoresis
Sodium/vitamin C co-transporter isoform 2
Tumor necrosis factor-alpha
A.P.K.R and W.A.P. were responsible for the study concept and design and they prepared and wrote the manuscript. A.P.K.R., J.A.S., M.C.Q.S., A.K., E.M.S.S., T.S., A.H., C.K., and G.M. performed the experiments. L.S.F and M.F.M.R. helped in the Western blotting procedure and analysis. All authors approved the final manuscript.
This work was supported by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS—process 2010/1007354) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—process 870582/1997-5).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the Ethics Committee of the Universidade Federal do Rio Grande do Sul (CEUA-UFRGS #23352).
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