Atividades da nicotinamida, do ácido nicotínico e do nicorandil em modelos experimentais de inflamação articular: uma avaliação visando ao reposicionamento de fármacos

Abstract

Inflammatory joint diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and gout are chronic painful conditions that limit the quality of life of patients, whose importance increases with the population ageing phenomenon. The clinical and therapeutic management of these diseases still have limitations, and pain is usually reported by the patients as the most important symptom. Experimental models of articular inflammation allow investigation of the pathogenesis of the diseases, establishment of potential molecular targets for new drugs that can reduce the discomfort and prevent the progression of tissue destruction which accompanies these inflammatory processes and also to identifiy new pharmacotherapeutic alternatives. Nicotinamide and nicotinic acid, vitamins of the B complex, and nicorandil, a nitrated nicotinamide derivative, have been shown to exhibit activities is some pain and inflammation models. In scientific literature, there are no studies evaluating the effects induced by nicotinic acid, nicotinamide or nicorandil in models of joint inflammation. Nicotinamide (doses between 75 and 1000 mg/Kg, p.o.) and nicorandil (doses between 50 and 200 mg/Kg, p.o.) exhibited antiallodynic activity in experimental models of joint inflammation induced by CFA, zymosan and MSU. Nicorandil exhibited the most marked effect in all experimental models, characterized by a long lasting effect and efficacy even when sensitization was established. The investigation of possible mechanisms involved in this activity has shown that nicotinamide and nicorandil reduce neutrophil recruitment into the articular cavity and periarticular tissues in models of joint inflammation induced by zymosan and MSU. Nicotinamide and nicorandil reduced IL-1 and CXCL-1 production in the model of articular inflammation induced by MSU. Furthermore,, the antinociceptive effect induced by nicorandil was reversed by the previous administration of naltrexone (5 or 10 mg/Kg, i.p.) in the experimental model of joint inflammation induced by zymozan. The results of this study indicate that nicotinamide and especially nicorandil are drugs that should be further investigated aiming their repositioning in the pain management of patients with RA, OA and gout