VA Greater Los Angeles Healthcare System, LA, CA, USA.
Expert Rev Gastroenterol Hepatol. 2011 Feb;5(1):43-57. doi: 10.1586/egh.10.88.
Irritable bowel syndrome (IBS) is characterized by chronic, recurrent abdominal pain and altered bowel habits and is currently defined by symptom criteria and the absence of detectable organic disease. The underlying pathophysiology remains incompletely understood. Despite considerable efforts by the scientific community and the pharmaceutical industry to develop novel pharmacological treatments aimed at chronic visceral pain, the traditional approach to identifying and evaluating novel drugs for this target have largely failed to translate into effective IBS treatments. However, several novel drugs aimed at normalizing bowel movements have produced clinical effects, not only on the primary target, but also on pain and discomfort. While some of the commonly used experimental animal models for the pain dimension of IBS have some face and construct validity, the predictive validity of most of the models is either unknown, or has been disappointing. A reverse translational approach is proposed, which is based on identification and characterization of brain endophenotypes in patients, followed by translation of these endophenotypes for pharmacological studies in rodent models.
肠易激综合征（IBS）的特征为慢性、反复发作的腹痛和肠道习惯改变，目前通过症状标准和无明显器质性疾病来定义。其潜在的病理生理学仍不完全清楚。尽管科学界和制药行业做出了相当大的努力，开发针对慢性内脏疼痛的新型药理学治疗方法，但传统的方法在识别和评估针对这一靶点的新型药物方面，在很大程度上未能转化为有效的 IBS 治疗方法。然而，几种旨在使肠道运动正常化的新型药物不仅对主要靶点，而且对疼痛和不适都产生了临床效果。虽然一些常用于 IBS 疼痛维度的实验动物模型具有一定的表面和结构有效性，但大多数模型的预测有效性要么未知，要么令人失望。提出了一种反向转化方法，该方法基于在患者中识别和表征大脑内表型，然后将这些内表型转化为啮齿动物模型中的药理学研究。
