Abstract
Interstitial cystitis (IC) is a chronic symptom-complex characterized by pathological sensation of the bladder (i.e. bladder pain in addition to augmented sensory signals such as urinary frequency and urgency) without evidence of bacterial cystitis or other identifiable lower urinary tract disease. Patients with IC typically describe feeling the urge to void frequently, as well as pain in the bladder and/or urethra. The painful sensation may be described as burning, pressure, sharp, or aching, and is often difficult for the patient to localize precisely. Multiple theories as to the cause of IC have been proposed with varying degrees of evidence. The current body of literature supports the idea that IC is associated with an intrinsic pathology of the bladder urothelial cells. The identification and complete characterization of antiproliferative factor (APF), which is uniquely expressed by urothelial cells in bladders affected by IC, are major advances in the understanding of IC. Additionally, urothelial cells have been likened to neurons because of their ability to express neuronal receptors and release neurotransmitters. The purinergic pathway has been shown to be upregulated in urothelial cells in bladders affected by IC. These new findings should help to direct the development of newer clinical treatments for IC. A complete understanding of IC will only be possible with parallel advances in both basic and clinical sciences.
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References
Ratner V (2001) Interstitial cystitis: a chronic inflammatory bladder condition. World J Urol 19: 157–159
Gillenwater JY and Wein AJ (1988) Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28–29, 1987. J Urol 140: 203–206
Keay SK et al. (2001) Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis. Urology 57(6 Suppl 1): 9–14
Erickson DR et al. (2002) A comparison of multiple urine markers for interstitial cystitis. J Urol 167: 2461–2469
Keay S et al. (2003) Current and future directions in diagnostic markers in interstitial cystitis. Int J Urol 10 (Suppl): S27–S30
Erickson DR et al. (2004) Do the NIDDK cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol, in press
Waxman JA et al. (1998) Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation. J Urol 160:1663–1667
Keay S and Warren JW (1998) A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair. Med Hypotheses 51: 79–83
Nigro DA et al. (1997) Associations among cystoscopic and urodynamic findings for women enrolled in the Interstitial Cystitis Data Base (ICDB) Study. Urology 49(5A Suppl): 86–92
Kusek JW and Nyberg LM (2001) The epidemiology of interstitial cystitis: Is it time to expand our definition? Urology 57 (Suppl 6A): 95–99
Abrams P et al. (2002) The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 21: 167–178
Luzzi G and O'Leary M (1999) Chronic pelvic pain syndrome. Is common and poorly understood – a fresh approach is needed. Br Med J 318: 1227–1228
Parsons CL and Albo M (2002) Intravesical potassium sensitivity in patients with prostatitis. J Urol 168: 1054–1057
Dimitrakov JD (2001) A case of familial clustering of interstitial cystitis and chronic pelvic pain syndrome. Urology 58: 281
Keay S et al. (2004) Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome. Urology 63: 22–26
Yilmaz U et al. (2004) Intravesical potassium chloride sensitivity test in men with chronic pelvic pain syndrome. J Urol 172: 548–550
Oravisto KJ et al. (1970) Interstitial cystitis: clinical and immunological findings. Scand J Urol Nephrol 4: 37–42
Skoluda D et al. (1974) Kritische bemerkungen zur immunopathogenese der interstitiellen cystitis. Urologe 13: 15–23
Ruggieri MR et al. (1994) Current findings and future research avenues in the study of interstitial cystitis. Urol Clin North Am 21: 163–176
Keay S et al. (2000) Bladder epithelial cells from interstitial cystitis patients produce an inhibitor of HB-EGF production. J Urol 64: 2112–2118
Parsons CL et al. (1998) The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol 159: 1862–1866
Buffington CA and Woodworth BE (1997) Excretion of fluorescein in the urine of women with interstitial cystitis. J Urol 158: 786–789
Keay S et al. (2003) Changes in human bladder cell gene expression associated with interstitial cystitis or antiproliferative factor treatment. Physiol Genomics 14: 107–115
Keay S et al. (2003) Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis. Urology 61: 1278–1284
Sun Y et al. (2001) Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. J Urol 166: 1951–1956
Tempest HV et al. (2004) P2X2 and P2X3 receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int 93: 1344–1348
Sun Y and Chai TC (2004) Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171: 448–452
Keay SK et al. (2004) An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide. Proc Natl Acad Sci USA 101: 11803–11808
Seguchi T et al. (1992) Interleukin-6 activity in urine and serum in patients with bladder carcinoma. J Urol 148: 791–794
Rhee E et al. (1998) Urinary IL-6 is elevated in patients with urolithiasis. J Urol 160: 2284–2288
Davidoff R et al. (1997) Multiple urinary cytokine levels of bacterial cystitis. J Urol 157: 1980–1985
Chai TC et al. (2000) Bladder stretch alters urinary levels of HB-EGF and antiproliferative factor in interstitial cystitis patients. J Urol 163: 1440–1444
Chai TC et al. (2000) Percutaneous sacral 3rd nerve root (S3) neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in interstitial cystitis patients. Urology 55: 643–646
Birder LA et al. (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5: 856–860
Chess-Williams R (2002) Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol 22: 133–145
Stein RJ et al. (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 172: 1175–1178
Kumar V et al. (2004) Characteristics of adenosine triphosphatase release from porcine and human normal bladder. J Urol 172: 744–747
Birder LA et al. (1998) Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am J Physiol 275: F226–F229
Birder LA et al. (2002) Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci 22: 8063–8070
Logadottir YR et al. (2004) Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis. J Urol 171: 1148–1150
Burnstock G (1999) Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction. J Anat 194: 335–342
Ferguson DR et al. (1997) ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes–a possible sensory mechanism? J Physiol 505: 503–511
Palea S et al. (1993) Evidence for purinergic neurotransmission in human urinary bladder affected by interstitial cystitis. J Urol 150: 2007–2012
Freeman MR et al. (1997) Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. J Clin Invest 99: 1028–1036
Propert KJ et al. (2002) Pitfalls in the design of clinical trials for interstitial cystitis. Urology 60: 742–748
Sant GR et al. (2003) A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol 170: 810–815
Alexander RB et al. (2004) A randomized trial of ciprofloxacin and tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial. Ann Int Med 141: 581–589.
Payne C et al. (2004) Phase II safety and efficacy study of single dose of intravesical resiniferatoxin (RTX) in patients with interstitial cystitis [abstract]. Neurourol Urodyn 23: 606
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Susan Keay is one of the inventors on the patents for antiproliferative factor, the use of HB-EGF/EGF for diagnosis of IC, and the use of HB-EGF for treatment of IC.
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Chai, T., Keay, S. New theories in interstitial cystitis. Nat Rev Urol 1, 85–89 (2004). https://doi.org/10.1038/ncpuro0057
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DOI: https://doi.org/10.1038/ncpuro0057
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