Cystitis, Co-Morbid Disorders and Associated Epithelial Dysfunction

A variety of chronic pain syndromes share alterations in epithelial barrier or signaling functions. These epithelial cells can respond to a number of challenges, including environmental inputs and mediators released from nerves or nearby inflammatory cells, which can result in altered expression and/or sensitivity of various eceptor/channels as well as changes in release of mediators, all of which could impact normal function. Patients with PBS/IC exhibit increased association with certain chronic diseases and pain syndromes. It has been described that gastrointestinal disorders are common in relation to PBS/IC and many PBS/IC patients also describe symptoms of heartburn. One may speculate that shared disease mechanisms ("endophenotypes"), such as increased epithelial permeability and/or increased responsiveness of epithelial cells to mechanical and/or chemical stimuli exist in these disorders. In this regard, it has long been reported that augmented release of epithelial-derived ATP from "tubes and sacs"87 (such as the urinary bladder, ureter, gastrointestinal tract, and esophagus) may play a significant role in primary afferent sensitization in a number of pain-related diseases. Taken together, modification of the epithelium and/or loss of epithelial integrity in a number of pathological conditions can result in passage of irritating substances and/or release of neuroactive substances from the epithelium. These can lead to changes in the properties of sensory nerves and sensory symptoms.