Cystitis, co-morbid disorders and associated epithelial dysfunction.

Interstitial cystitis (painful bladder syndrome / interstitial cystitis; PBS/IC) is a persistent pain syndrome affecting the urinary bladder with symptoms including urinary frequency, bladder pain and nocturia.(–6) Various animal models have been studied, most of which mimic some aspect of the human condition of interest to the investigator(s). This review will provide examples of various animal models including those incorporating chronic stress, thought to produce features that share similarities to that of PBS/IC patients, whose symptoms are often exacerbated by various stressors. (–12) This review also provides evidence that patients with PBS/IC exhibit abnormalities within the bladder epithelium (or urothelium), even though a consistent relationship of such changes with symptom severity has not been demonstrated. These changes include alterations in urothelial integrity, differentiation and/or proliferation as well as changes in ‘sensory’ function (altered expression or sensitivity of receptors and ion channels). Establishing a diagnostic ‘indicator’ with a high degree of correlation in this syndrome would be of value in terms of disease status, diagnosis and treatment. There have been reports of a number of factors/mediators altered in PBS/IC. However, the lack of a validated biomarker and a well-defined etiology for this syndrome introduces a number of complications, including diagnostic confidence, choice of appropriate animal models to study basic mechanism with the goal toward treatment, and rational therapies. It is also becoming increasingly apparent that patients with PBS/IC often overlap or share symptoms commonly associated with other persistent pain disorders. These include (but are not limited to) irritable bowel syndrome (IBS), non-cardiac chest pain, fibromyalgia and even overactive bladder syndrome (OAB).(–18) Such types of changes are not limited to the urinary bladder, however, as reports of alterations in epithelial signaling/barrier function have been described in patients diagnosed with a wider variety of syndromes, including functional and inflammatory bowel disorders such as irritable bowel syndrome (IBS), gastrointestinal esophageal reflux disease (GERD) and asthma.(–21) These and other findings suggest that changes within the epithelium (barrier as well as signaling functions) may be a common occurrence that may contribute to peripheral mechanisms of hypersensitivity in a number of disorders.