Cardiovascular effects of chronic treatment with a β2-adrenoceptor agonist relieving neuropathic pain in mice

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 beta-AR agonists is effective against neuropathic allodynia. beta-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 beta-mimetics are cardiovascular. In this study, we compared the action of low doses of the selective beta(2)-AR agonist terbutaline and of a high dose of the mixed beta(1)/beta(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 beta-myosin heavy chain (Myh7). Our data show that a chronic treatment with the beta(2)-AR agonist terbutaline at low antiallodynic dose does not affect cardiovascular parameters, whereas the mixed beta(1)/beta(2)-AR agonist isoproterenol induces cardiac hypertrophy. These data suggest that low doses of beta(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. (C) 2011 Elsevier Ltd. All tights reserved.