Review article: molecular, pathological and therapeutic features of human enteric neuropathies

BACKGROUND: Considerable information has been gathered on the functional organization of enteric neuronal circuitries regulating gastrointestinal motility. However, little is known about the neuropathophysiological mechanisms underlying gastrointestinal motor disorders. AIM: To analyse the most important pathological findings, clinical implications and therapeutic management of idiopathic enteric neuropathies. METHODS: PubMed searches were used to retrieve the literature inherent to molecular determinants, pathophysiological bases and therapeutics of gastrointestinal dysmotility, such as achalasia, gastroparesis, chronic intestinal pseudo-obstruction, Hirschsprung's disease and slow transit constipation, to unravel advances on digestive disorders resulting from enteric neuropathies. RESULTS: Current data on molecular and pathological features of enteric neuropathies indicate that degenerative and inflammatory abnormalities can compromise the morpho-functional integrity of the enteric nervous system. These alterations lead to a massive impairment in gut transit and result in severe abdominal symptoms with associated high morbidity, poor quality of life for patients and established mortality. Many pathophysiological aspects of these severe conditions remain obscure, and therefore treatment options are quite limited and often unsatisfactory. CONCLUSIONS: This review of enteric nervous system abnormalities provides a framework to better understand the pathological processes underlying gut dysmotility, to translate this knowledge into clinical management and to foster the development of targeted therapeutic strategies.