Effect of atorvastatin, a HMG-CoA reductase inhibitor in monosodium iodoacetate-induced osteoarthritic pain: Implication for osteoarthritis therapy

Background: Oxidative stress is one of the main causes of pain and cartilage degradation in osteoarthritis. This study on atorvastatin, a HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease aimed to investigate its effect on hyperalgesia and cartilage damage in monosodium iodoacetate (MIA)-induced osteoarthritis model in rats. Methods: Osteoarthritis was induced by a single intra-articular injection of 3 mg MIA. After daily administration of atorvastatin (3, 10 and 30 mg/kg) for 20 days by oral gavage, pain was assessed on days 0, 1, 3, 7, 14 and 21. Histopathology of ipsilateral knee joint; oxidative markers and antioxidants in plasma were assessed on day 21. Results: Atorvastatin attenuated hyperalgesia. The increased level of lipid peroxidation, superoxide, protein carbonyl; decreased activity of catalase, glutathione-S-transferase, reduced glutathione and total thiol levels in MIA rats were restored to the normal levels, however, superoxide dismutase and nitric oxide levels remained unaltered by atoivastatin. Further, atorvastatin reduced the MIA-induced histopathological alteration in the knee joint. Conclusion: Our study demonstrated that atorvastatin attenuates MIA-induced osteoarthritic pain and protect cartilage degradation through inhibition of oxidative stress suggesting its importance in osteoarthritic pain management. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.