Antinociception induced by rosuvastatin in murine neuropathic pain

Pharmacol Rep. 2018 Jun;70(3):503-508. doi: 10.1016/j.pharep.2017.11.012. Epub 2017 Nov 22.

Abstract

Background: Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated.

Methods: A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models.

Results: PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia.

Conclusion: The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain.

Keywords: Antinociception; Neuropathy; Rosuvastatin; Spinal cord biomarkers.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Rosuvastatin Calcium / pharmacology*
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Spinal Cord / drug effects

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-1beta
  • Rosuvastatin Calcium
  • Glutathione
  • Glutathione Disulfide