Antinociception and Anti-Inflammation Induced by Simvastatin in Algesiometric Assays in Mice

Statins, belonging to a well-known drug class used for lowering cholesterol through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also have other pleiotropic properties, such as anti-inflammatory action. The purpose of this study was to evaluate the antinociceptive and anti-inflammatory effects of simvastatin in five models of nociceptive behaviour. Oral gavage administration of simvastatin induced a dose-dependent inhibition of nociception for 1 day in the acetic acid writhing (ED50 = 5.59 +/- 0.07), tail-flick (ED50 = 112.96 +/- 8.00), hot-plate (ED50 = 134.87 +/- 2.20), formalin hind paw (ED50 = 19.86 +/- 1.12 in phase I and 23.30 +/- 2.05 in phase II) and orofacial formalin (ED50 = 5.54 +/- 2.74 in phase I and 11.48 +/- 1.88 in phase II) tests. However, after 3 days, the values were in the acetic acid writhing (ED50 = 6.14 +/- 0.51), tail-flick (ED50 = 154 +/- 8.88), hot-plate (ED50 = 136.14 +/- 2.94), formalin hind paw (ED50 = 15.93 +/- 0.42 in phase I and 17.10 +/- 1.80 in phase II) and orofacial formalin (ED50 = 6.79 +/- 0.66 in phase I and 5.80 +/- 1.49 in phase II) tests. This study demonstrated the antinociceptive and anti-inflammatory activities of simvastatin in five models of tonic or phasic pain. These actions seem to be related to the inhibition of cytokine and prostanoid release and stimulation of nitric oxide synthesis. A possible clinical role of simvastatin could be related to the potentially beneficial effects in the neuropathic pain, and by their pleiotropic properties, they could play a clinical role in anti-inflammatory disease.