, Volume 26, Issue 3, pp 793–804 | Cite as

Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats

  • Claudia Rita Corso
  • Daniel Fernandes Martins
  • Stephanie Carvalho Borges
  • Olair Carlos Beltrame
  • José Ederaldo Queiroz Telles
  • Nilza Cristina Buttow
  • Maria Fernanda de Paula Werner
Original Article


The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.


Simvastatin Neuropathic pain Sciatic nerve Neuroprotection Mevalonate 



This work was supported by Grants from Fundação Araucária (672/2014). C.R. Corso thanks the master’s scholarship of CAPES.

Compliance with ethical standards

Conflict of interest

The authors declare that there was no conflict of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Claudia Rita Corso
    • 1
  • Daniel Fernandes Martins
    • 2
  • Stephanie Carvalho Borges
    • 3
  • Olair Carlos Beltrame
    • 4
  • José Ederaldo Queiroz Telles
    • 5
  • Nilza Cristina Buttow
    • 3
  • Maria Fernanda de Paula Werner
    • 1
  1. 1.Department of Pharmacology, (UFPR), Biological Science SectorFederal University of ParanaCuritibaBrazil
  2. 2.Post-Graduate Program in Health ScienceUNISULPalhoçaBrazil
  3. 3.Department of Morphological SciencesState University of MaringaMaringaBrazil
  4. 4.Department of Veterinary MedicineFederal University of ParanaCuritibaBrazil
  5. 5.Department of Medical PathologyFederal University of ParanaCuritibaBrazil

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