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 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 β2-AR agonist terbutaline and of a high dose of the mixed β1/β2-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 β2-AR agonist terbutaline at low antiallodynic dose does not affect cardiovascular parameters, whereas the mixed β1/β2-AR agonist isoproterenol induces cardiac hypertrophy. These data suggest that low doses of β2-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.

► Low dose β-AR agonists are preclinically effective against neuropathic allodynia.
► We assessed cardiovascular side-effects at antiallodynic therapeutic doses.
► Terbutaline treatment did not affect cardiac parameters while isoprenaline did.