Statins alleviate experimental nerve injury-induced neuropathic pain

Pain. 2011 May;152(5):1033-1043. doi: 10.1016/j.pain.2011.01.006.


The statins are a well-established class of drugs that lower plasma cholesterol levels by inhibiting HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase. They are widely used for the treatment of hypercholesterolemia and for the prevention of coronary heart disease. Recent studies suggest that statins have anti-inflammatory effects beyond their lipid-lowering properties. We sought to investigate whether statins could affect neuropathic pain by mediating nerve injury-associated inflammatory responses. The effects of hydrophilic rosuvastatin and lipophilic simvastatin were examined in the mouse partial sciatic nerve ligation model. Systemic daily administration of either statin from days 0 to 14 completely prevented the development of mechanical allodynia and thermal hyperalgesia. When administered from days 8 to 14 after injury, both statins dose-dependently reduced established hypersensitivity. After treatment, the effects of the statins were washed out within 2 to 7 days, depending on dose. Effects of both statins in alleviating mechanical allodynia were further confirmed in a different injury-associated neuropathic pain model, mental nerve chronic constriction, in rats. Both statins were able to abolish interleukin-1β expression in sciatic nerve triggered by nerve ligation. Additionally, quantitative analysis with Iba-1 and glial fibrillary acid protein immunoreactivity demonstrated that rosuvastatin and simvastatin significantly reduced the spinal microglial and astrocyte activation produced by sciatic nerve injury. The increase of interleukin-1β mRNA in the ipsilateral side of spinal cords was also reduced by the treatment of either statin. We identified a potential new application of statins in the treatment of neuropathic pain. The pain-alleviating effects of statins are likely attributable to their immunomodulatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cholesterol / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fluorobenzenes / therapeutic use*
  • Functional Laterality
  • Glial Fibrillary Acidic Protein / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperalgesia / drug therapy
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuralgia / classification
  • Neuralgia / drug therapy*
  • Neuralgia / pathology
  • Neuralgia / physiopathology
  • Pain Measurement / methods
  • Pain Threshold / drug effects
  • Pyrimidines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Rosuvastatin Calcium
  • Simvastatin / therapeutic use*
  • Sulfonamides / therapeutic use*


  • Fluorobenzenes
  • Glial Fibrillary Acidic Protein
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-1beta
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium
  • Cholesterol
  • Simvastatin