A role for corticotropin-releasing factor in functional gastrointestinal disorders

Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS), encompass a heterogeneous group of diseases identified by chronic or recurrent symptom-based diagnostic criteria. Psychosocial factors are key components in the outcome of clinical manifestations of IBS symptoms. Anxiogenic and endocrine responses to stress are mediated by the corticotropin-releasing factor (CRF)-CRF1 receptor pathway. Preclinical studies show that activation of the CRF1 receptor by exogenous CRF or stress recapitulates many functional symptoms of IBS diarrhea-predominant patients as related to anxiogenic/hypervigilant behavior, autonomic nervous system alterations, induction of diarrhea, visceral hyperalgesia, enhanced colonic motility, mucus secretion, increased permeability, bacterial translocation, and mast cell activation, which are all alleviated by selective CRF1 receptor antagonists. Clinical studies also support that CRF administration can induce IBS-like symptoms in healthy subjects and heighten colonic sensitivity in IBS patients. Yet to be ascertained is whether CRF1 receptor antagonists hold promise as a new therapy in IBS treatment.