Qian-Shen Kea, b, Hann-Chorng Kuoa, b
a Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
b Department of Urology, Tzu Chi University, Hualien, Taiwan
Abstract
Interstitial cystitis (IC) is a heterogeneous syndrome characterized by bladder pain and is associated with frequency and nocturia. Research findings have proposed several pathophysiological mechanisms including epithelial dysfunction, activation of mast cells, neurogenic inflammation, autoimmunity, and occult infection. One of the most common findings in IC bladders is denudation or thinning of the bladder epithelium, suggesting an altered regulation of urothelial homeostasis. Different phenotypes of IC have been explored including Hunner and nonHunner type IC (ulcer and nonulcer type IC), hypersensitive bladder, and bladder pain with and without functional somatic syndrome. Different gene expressions have been found in different IC phenotypes. Augmented purinergic signaling in the bladder has been found in IC. Significant increases in antiproliferative factor, decreases in heparin-binding epidermal growth factor, and increased levels of epidermal growth factor have been discovered. Abnormal cytokine secretion in IC bladders has also been related to an increase in purinergic signaling, which mediates increased bladder sensation. Abnormal expression of uroplakins, chondroitin sulfate, junction protein E-cadherin, and tight junctional protein zonula occludens-1, strongly suggests abnormal epithelial differentiation in IC bladders. The increased apoptosis of urothelium has been associated with increased tryptase activity and clinical bladder pain scores, suggesting chronic inflammation, increased apoptosis, and abnormal urothelial function are closely associated in IC bladders. A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. These urothelial dysfunctions can be partially reversed after repeated bladder injections of botulinum toxin A. Multiple comorbidities and functional somatic syndromes are also found to associate with IC, together with increased sympathetic nervous system tonicity and increased serum proinflammatory proteins and cytokines. Thus, the pathogenesis of IC might be involved in systemic disorders. It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. IC might be considered a progressive disease that evolves from early stage to late stage bladder conditions. Insult to the visceral organ initiates an inflammatory process, causing urothelial dysfunction in the bladder. The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. The sensory impulses also ascend to the corresponding cortical gyrus. Patients might have an early inflammatory reaction and produce characteristic IC symptoms, including bladder pain, urgency, frequency, and a positive potassium chloride sensitivity test. If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.
Keywords
Apoptosis; Bladder pain; Inflammation; Interstitial cystitis; Urothelial dysfunction
