E A Mayer1, K Tillisch, S Bradesi. 1. Department of Medicine, Center for Neurovisceral Sciences and Women's Health, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. emayer@ucla.edu
Abstract
BACKGROUND: The importance of bi-directional brain-gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain-gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia. METHODS: A literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006. RESULTS: Existing data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non-selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain-gut axis such as neurokinin, somatostatin and corticotropin-releasing factor receptor antagonists are promising. CONCLUSIONS: This review discusses the rationale for modulation of the brain-gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.
BACKGROUND: The importance of bi-directional brain-gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain-gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia. METHODS: A literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006. RESULTS: Existing data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non-selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain-gut axis such as neurokinin, somatostatin and corticotropin-releasing factor receptor antagonists are promising. CONCLUSIONS: This review discusses the rationale for modulation of the brain-gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.
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