Brain-gut interactions: implications for newer therapy.

Despite their high prevalence and significant economic impact on the healthcare system, functional GI disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, thus not permitting to draw any conclusions about true efficacy of any particular treatment. The past several years have seen the rapid evolution of a new, comprehensive disease model, based on alterations in brain-gut interactions. Even though the precise mechanisms and sites underlying these alterations 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 cord (opioids, glutamate, CGRP, NK-1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine, acetylcholine). Regardless of the primary pathophysiology underlying functional GI disorders (i.e. central vs. peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may be effective.