, 45:9 | Cite as

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

  • Ana Paula Konzen RiffelEmail author
  • Jéssica Araújo de Souza
  • Maria do Carmo Quevedo Santos
  • Adarly Kroth
  • Elza Maria Santos da Silveira
  • Taina Scheid
  • Geórgia M. Dexheimer
  • Andréa Horst
  • Carolina Kolberg
  • Maria Flávia Marques Ribeiro
  • Luciano Stürmer de Fraga
  • Wania Aparecida Partata



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.


Phosphorylated p38 Phosphorylated Akt Chronic constriction injury Sciatic nerve 



Ascorbic acid


Protein kinase B


Analysis of variance


Chronic constriction injury


Ethics Committee of the Universidade Federal do Rio Grande do Sul




Glyceraldehyde-3-phosphate dehydrogenase




Potassium chloride




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


Author contributions

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.

Funding information

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.

Ethics approval

This study was approved by the Ethics Committee of the Universidade Federal do Rio Grande do Sul (CEUA-UFRGS #23352).


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Ana Paula Konzen Riffel
    • 1
    Email author
  • Jéssica Araújo de Souza
    • 1
  • Maria do Carmo Quevedo Santos
    • 1
  • Adarly Kroth
    • 2
  • Elza Maria Santos da Silveira
    • 1
  • Taina Scheid
    • 1
  • Geórgia M. Dexheimer
    • 3
  • Andréa Horst
    • 3
  • Carolina Kolberg
    • 4
  • Maria Flávia Marques Ribeiro
    • 1
  • Luciano Stürmer de Fraga
    • 1
  • Wania Aparecida Partata
    • 1
  1. 1.Departamento de FisiologiaInstituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Área Ciências da VidaUniversidade do Oeste de Santa CatarinaJoaçabaBrazil
  3. 3.UnivatesLajeadoBrazil
  4. 4.Faculdade da Serra GaúchaCaxias do SulBrazil

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