Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, 21 rue René Descartes, 67084 Strasbourg cedex, France.
Neuropharmacology. 2011 Jul-Aug;61(1-2):51-60. doi: 10.1016/j.neuropharm.2011.02.015. Epub 2011 Feb 23.
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.
神经病理性疼痛通常是一种慢性疾病，会导致身体残疾，且难以治疗。通过在坐骨神经主要分支周围放置聚乙烯套管来建立神经病理性疼痛的啮齿动物模型，我们已经表明，β-AR 激动剂的慢性治疗对神经病理性痛觉过敏是有效的。β-激动剂被广泛用于治疗哮喘和慢性阻塞性肺疾病，并且可能为神经病理性疼痛管理提供一个有趣的选择。β-激动剂慢性治疗最突出的不良反应是心血管方面的。在这项研究中，我们比较了低剂量选择性β(2)-AR 激动剂特布他林和高剂量混合β(1)/β(2)-AR 激动剂异丙肾上腺素在神经病理性疼痛情况下对心血管参数的作用。异丙肾上腺素被用作某些与心脏相关变化的阳性对照。通过超声心动图、血液动力学测量、纤维化和心脏肥大的组织学分析以及心房利钠肽（Nppa）、骨膜蛋白（Postn）、结缔组织生长因子（Ctgf）和β-肌球蛋白重链（Myh7）的实时定量 PCR 分析来研究心脏功能。我们的数据表明，低剂量β(2)-AR 激动剂特布他林的慢性治疗在抗痛觉过敏剂量下不会影响心血管参数，而混合β(1)/β(2)-AR 激动剂异丙肾上腺素则会引起心脏肥大。这些数据表明，低剂量的β(2)-AR 激动剂可能在神经病理性疼痛管理中提供一种副作用罕见的合适治疗方法。这项在动物模型中进行的研究需要在人类中进行临床验证。
