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

Abstract

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.

Neurodynamic Treatment Promotes Mechanical Pain Modulation in Sensory Neurons and Nerve Regeneration in Rats

“…Our previous studies have shown that NDT induces dose-dependent pro-regenerative and antiapoptotic effects on sensory and motor neuronal cell lines [ 44 ], but as far as we know, no data on MA and hyperalgesia modulation are available. In the current study, we aimed to investigate in vivo if the NDT modulates neuropathic pain and promotes motor sensory recovery after a nerve crush injury [ 45 , 46 ]. To further explore the relevance of possible pain modulation processes induced by NDT in the DRG, we adopted an ex vivo model of DRG organotypic explant which was subjected to neurodynamic treatment through a bioreactor previously validated for this purpose [ 44 ].…”

Statins and Neuropathic Pain: A Narrative Review

“…Summary of studies of mice and/or rats as a model for neuropathic pain and effects of statin drugs[59,63,[65][66][67][68][69] …”