Similar to preclinical studies of chronic psychological stress52, recent observations show that peripheral administration of CRF enhanced visceral sensorimotor function, epithelial permeability, hyperalgesia, mast cell activation and serotonin responses in health and in IBS patients52, acting through specific CRF receptors present in both, the small and the large intestine, and further supporting the contribution of local gut CRF signaling to the systemic response to stress. Here, CRH is linked to irritable bowel syndrome.