Brain-gut interactions: Implications for newer therapy

Despite their high prevalence and significant economic impact on the health care system, functional GI disorders have evaded successful therapy. Conven tional medical therapies are based on inadequate disease models, and the gr eat majority of published treatment trials are flawed in their design, thus not permitting to draw any conclusions about true efficacy of any particul ar treatment. The past several years have seen the rapid evolution of a new , comprehensive disease model, based on alterations in brain-gut interactio ns. Even though the precise mechanisms and sites underlying these alteratio ns remain incompletely understood, plausible targets for the development of effective pharmacologic treatment are receptors on peripheral terminals of visceral afferent nerves (opioids, serotonin), ion channels and receptors on dorsal horn neurons within the spinal cold (opioids, glutamate, CGRP, NK -1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin. catecholamines. dopamine, acetylcholin e). Regardless of the primary pathophysiology underlying functional GI diso rders (i.e. central vs peripheral), different pharmacological strategies ta rgeted at different sites in the periphery or within the central nervous sy stem may be effective.