Approaches to the Modulation of Abdominal Pain

Despite their high prevalence and significant economicimpact on the health care system, functional gastrointestinaldisorders have evaded successful therapy. Conventionalmedical therapies are based on inadequate disease models, and thegreat majority of published treatment trials are flawed in their design,permitting no conclusions to be drawn about the true efficacyof any particular treatment. During the past several years, a new,comprehensive disease model based on alterations in brain-gut interactionshas rapidly evolved. Even though the precise mechanismsand sites underlying these alterations remain incompletelyunderstood, plausible targets for the development of effectivepharmacological treatments are receptors on peripheral terminalsof visceral afferent nerves (opioids and serotonin), ion channelsand receptors on dorsal horn neurons within the spinal cord(opioids, glutamate, calcitonin gene-related peptide andneurokinin-1), and supraspinal targets in the brainstem withinthe limbic system and in the prefrontal cortex (serotonin, catecholamines,dopamine and acetylcholine). Regardless of the primarypathophysiology underlying functional gastrointestinaldisorders (ie, central versus peripheral), different pharmacologicalstrategies targeted at different sites in the periphery or within thecentral nervous system may become effective therapies in the future