Sinniger Valérie, Mouchet Patrick, Bonaz Bruno
Groupe d'Etudes du Stress et des Interactions Neuro-Digestives (GESIND; EA3744), France.
Life Sci. 2005 Oct 21;77(23):2927-41. doi: 10.1016/j.lfs.2005.05.030.
Nor-trimebutine is the main metabolite of trimebutine that is used in the treatment of patients with irritable bowel syndrome. Nor-trimebutine has a blocking activity on sodium channels and a potent local anesthetic effect. These properties were used to investigate the effect of nor-trimebutine on spinal neuronal activation induced by models of noxious somato-visceral stimulus and acute colonic inflammation. Nor-trimebutine was administered in rats either subcutaneously 30 min before intraperitoneal administration of acetic acid or intracolonically 30 min before intracolonic infusion of trinitrobenzenesulfonic acid. Abdominal contractions were counted for 1 h as a marker of abdominal pain. c-fos expression was used as a marker of neuronal activation and revealed by immunohistochemistry 1h after intraperitoneal acetic acid injection and 2 h after colonic inflammation. Nor-trimebutine decreased Fos expression in the thoraco-lumbar (peritoneal irritation) and lumbo-sacral (colonic inflammation) spinal cord in laminae I, IIo V, VII and X. This effect was also observed in the sacral parasympathetic nucleus after colonic inflammation. Nor-trimebutine induced a significant decrease of abdominal contractions following intraperitoneal acetic acid injection. These data may explain the effectiveness of trimebutine in the therapy of abdominal pain in the irritable bowel syndrome.
去甲曲美布汀是曲美布汀的主要代谢产物，用于治疗肠易激综合征患者。去甲曲美布汀对钠通道具有阻断活性，并具有强大的局部麻醉作用。利用这些特性研究了去甲曲美布汀对有害躯体-内脏刺激模型和急性结肠炎症诱导的脊髓神经元激活的影响。在大鼠腹腔注射醋酸前30分钟皮下注射去甲曲美布汀，或在结肠内注入三硝基苯磺酸前30分钟结肠内给药。计数腹部收缩1小时作为腹痛的指标。c-fos表达用作神经元激活的指标，并在腹腔注射醋酸后1小时和结肠炎症后2小时通过免疫组织化学检测。去甲曲美布汀可降低胸腰段（腹膜刺激）和腰骶段（结肠炎症）脊髓I、IIo V、VII和X层的Fos表达。在结肠炎症后的骶副交感神经核中也观察到了这种效应。腹腔注射醋酸后，去甲曲美布汀可显著减少腹部收缩。这些数据可能解释了曲美布汀治疗肠易激综合征腹痛的有效性。
