title: Cardiovascular effects of chronic treatment with a β2-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.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, 21 rue René Descartes, 67084 Strasbourg cedex, France.
authors.forename: Nada
authors.initials: N
authors.lastname: Choucair-Jaafar
authors.forename: Nadine
authors.initials: N
authors.lastname: Beetz
authors.forename: Ralf
authors.initials: R
authors.lastname: Gilsbach
authors.forename: Ipek
authors.initials: I
authors.lastname: Yalcin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Waltisperger
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Freund-Mercier
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000503:physiopathology; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2