Statins attenuate hyperalgesia and inflammation in experimentally induced acute and neuropathic pain in rats

Abstract

Background Available medications for the treatment of neuropathic pain, such as steroidal anti-inflammatory drugs and NSAIDs, were shown to be of limited therapeutic benefit. Objectives This study aimed to evaluate the analgesic and anti-inflammatory effects of atorvastatin and pravastatin in acute and neuropathic pain in rats. Materials and methods Acute and neuropathic pains were induced in rat models by means of subplantar carrageenan injection and partial sciatic nerve ligation (PSNL), respectively. The anti-inflammatory effect of statins was assessed by the reduction in plantar edema (at 0, 1, 2, and 3 h) and prolongation of paw withdrawal reaction time in response to thermal stimulation (at 0, 0.5, 1, 2, 3, and 4 h) after carrageenan injection. Atorvastatin (2, 4, or 8 mg/kg) and pravastatin (4, 8, or 12 mg/kg) were administered intraperitoneally 30 min before carrageenan injection. The effect of statins on neuropathic pain was assessed by prolongation of paw withdrawal reaction time in response to thermal stimulation evaluated at 0, 3, 6, 9, 12, 15, and 18 days after PSNL. Atorvastatin (2, 4, or 8 mg/kg) and pravastatin (4, 8, or 12 mg/kg) were administered orally for 18 consecutive days after PSNL. In addition, the effect of atorvastatin and pravastatin on total cholesterol and tumor necrosis factor-α levels was also assessed. Results Both atorvastatin and pravastatin ameliorated carrageenan-induced rat paw edema and prolonged withdrawal time in response to thermal-induced pain. Both statins were also effective in ameliorating neuropathic pain induced by PSNL. These effects were independent of statin-induced hypolipidemic action but were concomitant with reduction of serum tumor necrosis factor-α levels. Conclusion Atorvastatin and pravastatin demonstrated effective therapeutic potentials to reduce acute and chronic pain together with the associated inflammation and hyperalgesia independent of their hypolipidemic effect.