UCLA Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.
Dig Dis. 2009;27 Suppl 1:55-67. doi: 10.1159/000268122. Epub 2010 Mar 4.
The majority of functional gastrointestinal disorders are characterised by recurrent abdominal pain, with stress playing an important role in first onset and exacerbation of existing symptoms. These disorders are currently defined by symptom criteria, while their pathophysiology remains controversial and incompletely understood. Modeling these disorders in humans and animals has been difficult. While some of the models have adequate face and construct validity, the predictive validity of most of the models has been disappointing, which has put into question the traditional modeling approach. Similar problems have been encountered in drug development for pain and psychiatric disorders. New approaches have been proposed in the form of reverse translation, which include better characterisation of biological intermediate phenotypes in human disease which can be modeled in humans and in animals. Continuation of the current approach focusing on complex clinical phenotypes is likely to be ineffective for the development of novel and effect treatments.
大多数功能性胃肠疾病的特征是反复发作的腹痛,压力在疾病首次发作和现有症状恶化中起着重要作用。这些疾病目前是根据症状标准来定义的,但其病理生理学仍存在争议,尚未完全了解。在人类和动物中对这些疾病进行建模一直具有挑战性。虽然一些模型具有充分的表面和结构有效性,但大多数模型的预测有效性却令人失望,这对传统的建模方法提出了质疑。在疼痛和精神疾病的药物开发中也遇到了类似的问题。已经提出了新的反向翻译方法,包括更好地描述人类疾病中的生物学中间表型,这些表型可以在人类和动物中进行建模。继续采用目前专注于复杂临床表型的方法,可能对开发新型有效治疗方法无效。