Cardiovascular effects of chronic treatment with a β 2-adrenoceptor agonist relieving neuropathic pain in mice

Abstract

Neuropathic pain is often a chronic condition, disabling and difficult to treat. Using a murine model of neuropathic pain induced by placing a polyethylene cuff around the main branch of the sciatic nerve, we have shown that chronic treatment with β-AR agonists is effective against neuropathic allodynia. β-mimetics are widely used against asthma and chronic obstructive pulmonary disease and may offer an interesting option for neuropathic pain management. The most prominent adverse effects of chronic treatment with β-mimetics are cardiovascular. In this study, we compared the action of low doses of the selective β 2-AR agonist terbutaline and of a high dose of the mixed β 1/β 2-AR agonist isoproterenol on cardiovascular parameters in a neuropathic pain context. Isoproterenol was used as a positive control for some heart-related changes. Cardiac functions were studied by echocardiography, hemodynamic measurements, histological analysis of fibrosis and cardiac hypertrophy, and by quantitative real time PCR analysis of atrial natriuretic peptide ( Nppa), periostin ( Postn), connective tissue growth factor ( Ctgf) and β-myosin heavy chain ( Myh7). Our data show that a chronic treatment with the β 2-AR agonist terbutaline at low antiallodynic dose does not affect cardiovascular parameters, whereas the mixed β 1/β 2-AR agonist isoproterenol induces cardiac hypertrophy. These data suggest that low doses of β 2-AR agonists may provide a suitable treatment with rare side effects in neuropathic pain management. This study conducted in an animal model requires clinical confirmation in humans.