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Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome

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Abstract

Purpose

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer’s quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques.

Methods

A comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about “Interstitial cystitis” and “Painful Bladder Syndrome”. Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey.

Results

The etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no “gold standards” in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers.

Conclusion

Due to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

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References

  1. Hanno P, Nordling J, van Ophoven A (2008) What is new in bladder pain syndrome/interstitial cystitis? Curr Opin Urol 18:353–358. doi:10.1097/MOU.0b013e3282fcea88

    Article  PubMed  Google Scholar 

  2. Lukban JC, Parkin JV, Holzberg AS, Caraballo R, Kellogg-Spadt S, Whitmore KE (2001) Interstitial cystitis and pelvic floor dysfunction: a comprehensive review. Pain Med 2:60–71. doi:10.1046/j.1526-4637.2001.002001060.x

    Article  CAS  PubMed  Google Scholar 

  3. Ratner V, Perilli L (2003) Interstitial cystitis: an updated overview. Urol Nurs 23:107–110 (quiz 111)

    PubMed  Google Scholar 

  4. Nickel JC (2004) Interstitial cystitis: a chronic pelvic pain syndrome. Med Clin North Am 88(467–481):xii. doi:10.1016/S0025-7125(03)00151-2

    Google Scholar 

  5. Hanno P, Levin RM, Monson FC, Teuscher C, Zhou ZZ, Ruggieri M, Whitmore K, Wein AJ (1990) Diagnosis of interstitial cystitis. J Urol 143:278–281

    CAS  PubMed  Google Scholar 

  6. Hanno P, Keay S, Moldwin R, Van Ophoven A (2005) International Consultation on IC—Rome, September 2004/Forging an International Consensus: progress in painful bladder syndrome/interstitial cystitis. Report and abstracts. Int Urogynecol J Pelvic Floor Dysfunct 16(Suppl 1):S2–S34. doi:10.1007/s00192-005-1301-x

    Article  PubMed  Google Scholar 

  7. Kelada E, Jones A (2007) Interstitial cystitis. Arch Gynecol Obstet 275:223–229. doi:10.1007/s00404-006-0247-7

    Article  PubMed  Google Scholar 

  8. Parsons JK, Parsons CL (2004) The historical origins of interstitial cystitis. J Urol 171:20–22. doi:10.1097/01.ju.0000099890.35040.8d

    Article  PubMed  Google Scholar 

  9. Dell JR (2007) Interstitial cystitis/painful bladder syndrome: appropriate diagnosis and management. J Womens Health (Larchmt) 16:1181–1187. doi:10.1089/jwh.2006.0182

    Article  Google Scholar 

  10. Bogart LM, Berry SH, Clemens JQ (2007) Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. J Urol 177:450–456. doi:10.1016/j.juro.2006.09.032

    Article  PubMed  Google Scholar 

  11. Warren JW, Meyer WA, Greenberg P, Horne L, Diggs C, Tracy JK (2006) Using the International Continence Society’s definition of painful bladder syndrome. Urology 67:1138–1142; (discussion 1142-1133). doi:10.1016/j.urology.2006.01.086

    Article  PubMed  PubMed Central  Google Scholar 

  12. Proano A, Garde G, Garrido G, Mazza O (2013) ESSIC criteria for the diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) and comparison with the NIDDK criteria. Arch Esp Urol 66:206–214

    PubMed  Google Scholar 

  13. Bouchelouche K, Nordling J (2003) Recent developments in the management of interstitial cystitis. Curr Opin Urol 13:309–313. doi:10.1097/01.mou.0000079415.62186.a8

    Article  PubMed  Google Scholar 

  14. Powell TO (1950) Hunner ulcer; report of cases. West J Surg Obstet Gynecol 58:118–129

    CAS  PubMed  Google Scholar 

  15. Powell TO (1949) Treatment of hunner ulcer. Urol Cutaneous Rev 53:397–400

    CAS  PubMed  Google Scholar 

  16. Parsons CL, Walker CJ (1996) Cystoscopic changes in interstitial cystitis. Urology 48:289–290

    Article  CAS  PubMed  Google Scholar 

  17. Metts JF (2001) Interstitial cystitis: urgency and frequency syndrome. Am Fam Physician 64:1199–1206

    CAS  PubMed  Google Scholar 

  18. Burford EH, Burford CE (1958) Hunner ulcer of the bladder: a report of 187 cases. J Urol 79:952–955

    CAS  PubMed  Google Scholar 

  19. Weyeneth R, Rohner A (1961) Simple ulcer of the bladder. Interstitial ulcerous cystitis, Fenwick-Hunner ulcer. Schweiz Med Wochenschr 91:1042–1052

    CAS  PubMed  Google Scholar 

  20. Koziol JA, Adams HP, Frutos A (1996) Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings. J Urol 155:87–90. doi:10.1016/S0022-5347(01)66551-0

    Article  CAS  PubMed  Google Scholar 

  21. Killinger KA, Boura JA, Peters KM (2013) Pain in interstitial cystitis/bladder pain syndrome: do characteristics differ in ulcerative and non-ulcerative subtypes? Int Urogynecol J 24:1295–1301. doi:10.1007/s00192-012-2003-9

    Article  PubMed  Google Scholar 

  22. Zhang CO, Li ZL, Kong CZ (2005) APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis. BMC Urol 5:7. doi:10.1186/1471-2490-5-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Gamper M, Viereck V, Geissbuhler V, Eberhard J, Binder J, Moll C, Rehrauer H, Moser R (2009) Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis. BMC Genomics 10:199. doi:10.1186/1471-2164-10-199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Gamper M, Viereck V, Eberhard J, Binder J, Moll C, Welter J, Moser R (2013) Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3 C. Int Urogynecol J 24:2049–2057. doi:10.1007/s00192-013-2112-0

    Article  PubMed  PubMed Central  Google Scholar 

  25. Esteban M, Adot JM, Arlandis S, Peri L, Prieto L, Salinas J, Cozar JM; Working group for recommendations on the diagnosis and management of bladder pain syndrome (2015) Recommendations for the diagnosis and management of bladder pain syndrome. Spanish Urological Association Consensus Document. Actas Urol Esp 39:465–472. doi:10.1016/j.acuro.2015.01.006

    Article  CAS  PubMed  Google Scholar 

  26. Anger JT, Zabihi N, Clemens JQ, Payne CK, Saigal CS, Rodriguez LV (2011) Treatment choice, duration, and cost in patients with interstitial cystitis and painful bladder syndrome. Int Urogynecol J 22:395–400. doi:10.1007/s00192-010-1252-8

    Article  PubMed  Google Scholar 

  27. Wu EQ, Birnbaum H, Mareva M, Parece A, Huang Z, Mallett D, Taitel H (2006) Interstitial Cystitis: Cost, treatment and co-morbidities in an employed population. Pharmacoeconomics 24:55–65

    Article  PubMed  Google Scholar 

  28. Stanford EJ, Chen A, Wan GJ, Lunacsek OE, Sand PK (2008) Treatment modalities, health care resource utilization, and costs in patients diagnosed with interstitial cystitis. Am J Obstet Gynecol 199(71):e1–e10. doi:10.1016/j.ajog.2008.02.048

    Google Scholar 

  29. Wu EQ, Birnbaum H, Kang YJ, Parece A, Mallett D, Taitel H, Evans RJ (2006) A retrospective claims database analysis to assess patterns of interstitial cystitis diagnosis. Curr Med Res Opin 22:495–500. doi:10.1185/030079906X80431

    Article  PubMed  Google Scholar 

  30. Riedl C, Engelhardt P, Schwarz B (2013) Treatment costs of bladder pain syndrome/interstitial cystitis in Austria: a pharmacoeconomic approach following current guidelines. Clin Drug Investig 33:737–742. doi:10.1007/s40261-013-0119-4

    Article  PubMed  Google Scholar 

  31. Clemens JQ, Meenan RT, Rosetti MC, Kimes T, Calhoun EA (2008) Costs of interstitial cystitis in a managed care population. Urology 71:776–780; (discussion 780-771). doi:10.1016/j.urology.2007.11.154

    Article  PubMed  PubMed Central  Google Scholar 

  32. Yoost JL, Hertweck SP, Loveless M (2012) Diagnosis and treatment of interstitial cystitis in adolescents. J Pediatr Adolesc Gynecol 25:162–171. doi:10.1016/j.jpag.2011.03.011

    Article  CAS  PubMed  Google Scholar 

  33. Kahn BS, Tatro C, Parsons CL, Willems JJ (2010) Prevalence of interstitial cystitis in vulvodynia patients detected by bladder potassium sensitivity. J Sex Med 7:996–1002. doi:10.1111/j.1743-6109.2009.01550.x

    Article  PubMed  Google Scholar 

  34. Patel R, Calhoun EA, Meenan RT, O’Keeffe Rosetti MC, Kimes T, Clemens JQ (2008) Incidence and clinical characteristics of interstitial cystitis in the community. Int Urogynecol J Pelvic Floor Dysfunct 19:1093–1096. doi:10.1007/s00192-008-0573-3

    Article  PubMed  PubMed Central  Google Scholar 

  35. Peters KM, Carrico DJ, Diokno AC (2008) Characterization of a clinical cohort of 87 women with interstitial cystitis/painful bladder syndrome. Urology 71:634–640. doi:10.1016/j.urology.2007.11.013

    Article  PubMed  Google Scholar 

  36. Cheng C, Rosamilia A, Healey M (2012) Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic pelvic pain: a prospective observational study. Int Urogynecol J 23:1361–1366. doi:10.1007/s00192-012-1711-5

    Article  PubMed  Google Scholar 

  37. Theoharides TC, Whitmore K, Stanford E, Moldwin R, O’Leary MP (2008) Interstitial cystitis: bladder pain and beyond. Expert Opin Pharmacother 9:2979–2994. doi:10.1517/14656560802519845

    Article  CAS  PubMed  Google Scholar 

  38. Panzera AK, Reishtein J, Shewokis P (2011) Sleep disruption and interstitial cystitis symptoms in women. Urol Nurs 31(159–165):172

    Google Scholar 

  39. Teichman JM, Parsons CL (2007) Contemporary clinical presentation of interstitial cystitis. Urology 69:41–47. doi:10.1016/j.urology.2006.08.1111

    Article  PubMed  Google Scholar 

  40. Gardella B, Porru D, Ferdeghini F, Martinotti Gabellotti E, Nappi RE, Rovereto B, Spinillo A (2008) Insight into urogynecologic features of women with interstitial cystitis/painful bladder syndrome. Eur Urol 54:1145–1151. doi:10.1016/j.eururo.2008.01.079

    Article  PubMed  Google Scholar 

  41. Powell-Boone T, Ness TJ, Cannon R, Lloyd LK, Weigent DA, Fillingim RB (2005) Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis. J Urol 174:1832–1836. doi:10.1097/01.ju.0000176747.40242.3d

    Article  PubMed  Google Scholar 

  42. Hanno PM, Chapple CR, Cardozo LD (2009) Bladder pain syndrome/interstitial cystitis: a sense of urgency. World J Urol 27:717–721. doi:10.1007/s00345-009-0439-4

    Article  PubMed  Google Scholar 

  43. El Khoudary SR, Talbott EO, Bromberger JT, Chang CC, Songer TJ, Davis EL (2009) Severity of interstitial cystitis symptoms and quality of life in female patients. J Womens Health (Larchmt) 18:1361–1368. doi:10.1089/jwh.2008.1270

    Article  Google Scholar 

  44. Tripp DA, Nickel JC, Fitzgerald MP, Mayer R, Stechyson N, Hsieh A (2009) Sexual functioning, catastrophizing, depression, and pain, as predictors of quality of life in women with interstitial cystitis/painful bladder syndrome. Urology 73:987–992. doi:10.1016/j.urology.2008.11.049

    Article  PubMed  Google Scholar 

  45. Caruso S, Bandiera S, Cavallaro A, Cianci S, Vitale SG, Rugolo S (2010) Quality of life and sexual changes after double transobturator tension-free approach to treat severe cystocele. Eur J Obstet Gynecol Reprod Biol 151:106–109. doi:10.1016/j.ejogrb.2010.03.016

    Article  PubMed  Google Scholar 

  46. Vitale SG, Caruso S, Rapisarda AM, Valenti G, Rossetti D, Cianci S, Cianci A (2016) Biocompatible porcine dermis graft to treat severe cystocele: impact on quality of life and sexuality. Arch Gynecol Obstet 293:125–131. doi:10.1007/s00404-015-3820-0

    Article  PubMed  Google Scholar 

  47. Fiander N (2013) Painful bladder syndrome and interstitial cystitis: treatment options. Br J Nurs 22(S26):S28–S33

    Google Scholar 

  48. Lee MH, Lin AT, Kuo HC, Chen YF (2014) Clinical Characteristic Picture and Impact of Symptoms on Quality of Life of Interstitial Cystitis Patients in Taiwan. Low Urin Tract Symptoms 6:20–25. doi:10.1111/luts.12013

  49. Temml C, Wehrberger C, Riedl C, Ponholzer A, Marszalek M, Madersbacher S (2007) Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project. Eur Urol 51:803–808; discussion 809. doi:10.1016/j.eururo.2006.08.028

    Article  PubMed  Google Scholar 

  50. Michael YL, Kawachi I, Stampfer MJ, Colditz GA, Curhan GC (2000) Quality of life among women with interstitial cystitis. J Urol 164:423–427. doi:10.1016/S0022-5347(05)67376-4

    Article  CAS  PubMed  Google Scholar 

  51. Ginting JV, Tripp DA, Nickel JC, Fitzgerald MP, Mayer R (2011) Spousal support decreases the negative impact of pain on mental quality of life in women with interstitial cystitis/painful bladder syndrome. BJU Int 108:713–717. doi:10.1111/j.1464-410X.2010.09846.x

    PubMed  Google Scholar 

  52. Birder LA, Hanna-Mitchell AT, Mayer E, Buffington CA (2011) Cystitis, co-morbid disorders and associated epithelial dysfunction. Neurourol Urodyn 30:668–672. doi:10.1002/nau.21109

    Article  PubMed  PubMed Central  Google Scholar 

  53. Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J (2010) Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. J Urol 184:1358–1363. doi:10.1016/j.juro.2010.06.005

    Article  PubMed  Google Scholar 

  54. Buffington CA (2004) Comorbidity of interstitial cystitis with other unexplained clinical conditions. J Urol 172:1242–1248. doi:10.1097/01.ju.0000137953.49304.6c

    Article  PubMed  Google Scholar 

  55. Peters KM, Killinger KA, Mounayer MH, Boura JA (2011) Are ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome 2 distinct diseases? A study of coexisting conditions. Urology 78:301–308. doi:10.1016/j.urology.2011.04.030

    Article  PubMed  Google Scholar 

  56. Peeker R, Aldenborg F, Haglid K, Johansson SL, Rosengren L, Fall M (1998) Decreased levels of S-100 protein in non-ulcer interstitial cystitis. Scand J Urol Nephrol 32:395–398. doi:10.1080/003655998750015179

    Article  CAS  PubMed  Google Scholar 

  57. Fall M, Johansson SL, Aldenborg F (1987) Chronic interstitial cystitis: a heterogeneous syndrome. J Urol 137:35–38

    CAS  PubMed  Google Scholar 

  58. Lundeberg T, Liedberg H, Nordling L, Theodorsson E, Owzarski A, Ekman P (1993) Interstitial cystitis: correlation with nerve fibres, mast cells and histamine. Br J Urol 71:427–429. doi:10.1111/j.1464-410x.1993.tb15986.x

    Article  CAS  PubMed  Google Scholar 

  59. Enerback L, Fall M, Aldenborg F (1989) Histamine and mucosal mast cells in interstitial cystitis. Agents Actions 27:113–116. doi:10.1007/bf02222214

    Article  CAS  PubMed  Google Scholar 

  60. Logadottir Y, Hallsberg L, Fall M, Peeker R, Delbro D (2013) Bladder pain syndrome/interstitial cystitis ESSIC type 3C: high expression of inducible nitric oxide synthase in inflammatory cells. Scand J Urol 47:52–56. doi:10.3109/00365599.2012.699100

    Article  CAS  PubMed  Google Scholar 

  61. Peeker R, Fall M (2000) Treatment guidelines for classic and non-ulcer interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct 11:23–32. doi:10.1007/s001920050006

    Article  CAS  PubMed  Google Scholar 

  62. Peeker R, Fall M (2002) Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol 167:2470–2472. doi:10.1016/S0022-5347(05)65006-9

    Article  PubMed  Google Scholar 

  63. Stanford EJ, Dell JR, Parsons CL (2007) The emerging presence of interstitial cystitis in gynecologic patients with chronic pelvic pain. Urology 69:53–59. doi:10.1016/j.urology.2006.05.049

    Article  PubMed  Google Scholar 

  64. Chuang YC, Lee WC, Lee WC, Chiang PH (2009) Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol 182:1393–1400. doi:10.1016/j.juro.2009.06.024

    Article  CAS  PubMed  Google Scholar 

  65. Bogart LM, Suttorp MJ, Elliott MN, Clemens JQ, Berry SH (2011) Prevalence and correlates of sexual dysfunction among women with bladder pain syndrome/interstitial cystitis. Urology 77:576–580. doi:10.1016/j.urology.2010.10.016

    Article  PubMed  PubMed Central  Google Scholar 

  66. Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ (2012) Contemporary management of the painful bladder: a systematic review. Eur Urol 61:29–53. doi:10.1016/j.eururo.2011.07.069

    Article  PubMed  Google Scholar 

  67. Atchley MD, Shah NM, Whitmore KE (2015) Complementary and alternative medical therapies for interstitial cystitis: an update from the United States. Transl Androl Urol 4:662–667. doi:10.3978/j.issn.2223-4683.2015.08.08

    PubMed  PubMed Central  Google Scholar 

  68. Rosa ESJC, Pazin C, Silva A, Mitidieri AM, Gurian MB (2015) Treatment of bladder pain syndrome and interstitial cystitis: a systematic review. J Minim Invasive Gynecol 22:S244. doi:10.1016/j.jmig.2015.08.854

    Article  Google Scholar 

  69. Hoke TP, Goldstein H, Saks EK, Vakili B (2016) Hydrodistention of the bladder for the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Neurourol Urodyn. doi:10.1002/nau.23024

    PubMed  Google Scholar 

  70. Kuo HC, Jiang YH, Tsai YC, Kuo YC (2016) Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment—a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Neurourol Urodyn 35:609–614. doi:10.1002/nau.22760

    Article  CAS  PubMed  Google Scholar 

  71. Sant GR (2002) Etiology, pathogenesis, and diagnosis of interstitial cystitis. Rev Urol 4(Suppl 1):S9–S15

    PubMed  PubMed Central  Google Scholar 

  72. Parsons JK, Kurth K, Sant GR (2007) Epidemiologic issues in interstitial cystitis. Urology 69:5–8. doi:10.1016/j.urology.2006.05.050

    Article  PubMed  Google Scholar 

  73. Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Willems JJ (2002) The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity. Am J Obstet Gynecol 187:1395–1400. doi:10.1067/mob.2002.127375

    Article  PubMed  Google Scholar 

  74. Berry SH, Elliott MN, Suttorp M, Bogart LM, Stoto MA, Eggers P, Nyberg L, Clemens JQ (2011) Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol 186:540–544. doi:10.1016/j.juro.2011.03.132

    Article  PubMed  PubMed Central  Google Scholar 

  75. Konkle KS, Berry SH, Elliott MN, Hilton L, Suttorp MJ, Clauw DJ, Clemens JQ (2012) Comparison of an interstitial cystitis/bladder pain syndrome clinical cohort with symptomatic community women from the RAND Interstitial Cystitis Epidemiology study. J Urol 187:508–512. doi:10.1016/j.juro.2011.10.040

    Article  PubMed  Google Scholar 

  76. Tincello DG, Walker AC (2005) Interstitial cystitis in the UK: results of a questionnaire survey of members of the Interstitial Cystitis Support Group. Eur J Obstet Gynecol Reprod Biol 118:91–95. doi:10.1016/j.ejogrb.2004.06.012

    Article  PubMed  Google Scholar 

  77. Rosenberg MT, Hazzard M (2005) Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office. J Urol 174:2231–2234. doi:10.1097/01.ju.0000181203.82693.95

    Article  PubMed  Google Scholar 

  78. Roberts RO, Bergstralh EJ, Bass SE, Lightner DJ, Lieber MM, Jacobsen SJ (2003) Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study. BJU Int 91:181–185

    Article  CAS  PubMed  Google Scholar 

  79. Parsons CL, Tatsis V (2004) Prevalence of interstitial cystitis in young women. Urology 64:866–870. doi:10.1016/j.urology.2004.06.044

    Article  PubMed  Google Scholar 

  80. Parsons CL (2002) Interstitial cystitis: epidemiology and clinical presentation. Clin Obstet Gynecol 45:242–249. doi:10.1097/00003081-200203000-00025

    Article  PubMed  Google Scholar 

  81. Oravisto KJ (1975) Epidemiology of interstitial cystitis. Ann Chir Gynaecol Fenn 64(2):75–77

    CAS  PubMed  Google Scholar 

  82. Nickel JC, Teichman JM, Gregoire M, Clark J, Downey J (2005) Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study. Urology 66:935–940. doi:10.1016/j.urology.2005.05.007

    Article  PubMed  Google Scholar 

  83. Leppilahti M, Tammela TL, Huhtala H, Auvinen A (2002) Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland. J Urol 168:139–143. doi:10.1016/s0022-5347(05)64847-1

    Article  PubMed  Google Scholar 

  84. Leppilahti M, Sairanen J, Tammela TL, Aaltomaa S, Lehtoranta K, Auvinen A; Finnish Interstitial Cystitis-Pelvic Pain Syndrome Study Group (2005) Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland. J Urol 174:581–583. doi:10.1097/01.ju.0000165452.39125.98

    Article  PubMed  Google Scholar 

  85. Kusek JW, Nyberg LM (2001) The epidemiology of interstitial cystitis: is it time to expand our definition? Urology 57:95–99. doi:10.1016/s0090-4295(01)01141-4

    Article  CAS  PubMed  Google Scholar 

  86. Jones CA, Nyberg L (1997) Epidemiology of interstitial cystitis. Urology 49:2–9. doi:10.1016/s0090-4295(99)80327-6

    Article  CAS  PubMed  Google Scholar 

  87. Ito T, Miki M, Yamada T (2000) Interstitial cystitis in Japan. BJU Int 86(6):634–637. doi:10.1046/j.1464-410x.2000.00855.x

    Article  CAS  PubMed  Google Scholar 

  88. Ibrahim IA, Diokno AC, Killinger KA, Carrico DJ, Peters KM (2007) Prevalence of self-reported interstitial cystitis (IC) and interstitial-cystitis-like symptoms among adult women in the community. Int Urol Nephrol 39:489–495. doi:10.1007/s11255-007-9181-2

    Article  PubMed  Google Scholar 

  89. Hanno PM (2002) Interstitial cystitis-epidemiology, diagnostic criteria, clinical markers. Rev Urol 4(Suppl 1):S3–S8

    PubMed  PubMed Central  Google Scholar 

  90. Hanno P, Dmochowski R (2009) Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn 28:274–286. doi:10.1002/nau.20687

    Article  PubMed  Google Scholar 

  91. Curhan GC, Speizer FE, Hunter DJ, Curhan SG, Stampfer MJ (1999) Epidemiology of interstitial cystitis: a population based study. J Urol 161:549–552. doi:10.1016/s0022-5347(01)61947-5

    Article  CAS  PubMed  Google Scholar 

  92. Clemens JQ, Meenan RT, Rosetti MC, Gao SY, Calhoun EA (2005) Prevalence and incidence of interstitial cystitis in a managed care population. J Urol 173:98–102; discussion 102. doi:10.1097/01.ju.0000146114.53828.82

    Article  PubMed  Google Scholar 

  93. Clemens JQ, Meenan RT, O’Keeffe Rosetti MC, Brown SO, Gao SY, Calhoun EA (2005) Prevalence of interstitial cystitis symptoms in a managed care population. J Urol 174:576–580. doi:10.1097/01.ju.0000165170.43617.be

    Article  PubMed  Google Scholar 

  94. Bade JJ, Rijcken B, Mensink HJ (1995) Interstitial cystitis in The Netherlands: prevalence, diagnostic criteria and therapeutic preferences. J Urol 154:2035–2037; discussion 2037–2038. doi:10.1016/s0022-5347(01)66684-9

    Article  CAS  PubMed  Google Scholar 

  95. Clemens JQ, Link CL, Eggers PW, Kusek JW, Nyberg LM Jr, McKinlay JB, Investigators BS (2007) Prevalence of painful bladder symptoms and effect on quality of life in black, Hispanic and white men and women. J Urol 177:1390–1394. doi:10.1016/j.juro.2006.11.084

    Article  PubMed  Google Scholar 

  96. Barry MJ, Link CL, McNaughton-Collins MF, McKinlay JB, Boston Area Community Health I (2008) Overlap of different urological symptom complexes in a racially and ethnically diverse, community-based population of men and women. BJU Int 101:45–51. doi:10.1111/j.1464-410X.2007.07191.x

    PubMed  Google Scholar 

  97. Lifford KL, Curhan GC (2009) Prevalence of painful bladder syndrome in older women. Urology 73:494–498. doi:10.1016/j.urology.2008.01.053

    Article  PubMed  Google Scholar 

  98. Simon LJ, Landis JR, Erickson DR, Nyberg LM (1997) The Interstitial Cystitis Data Base Study: concepts and preliminary baseline descriptive statistics. Urology 49:64–75. doi:10.1016/s0090-4295(99)80334-3

    Article  CAS  PubMed  Google Scholar 

  99. Chelimsky G, Heller E, Buffington CA, Rackley R, Zhang D, Chelimsky T (2012) Co-morbidities of interstitial cystitis. Front Neurosci 6:114. doi:10.3389/fnins.2012.00114

    Article  PubMed  PubMed Central  Google Scholar 

  100. Alagiri M, Chottiner S, Ratner V, Slade D, Hanno PM (1997) Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes. Urology 49:52–57. doi:10.1016/s0090-4295(99)80332-x

    Article  CAS  PubMed  Google Scholar 

  101. Clemens JQ, Elliott MN, Suttorp M, Berry SH (2012) Temporal ordering of interstitial cystitis/bladder pain syndrome and non-bladder conditions. Urology 80:1227–1231. doi:10.1016/j.urology.2012.06.059

    Article  PubMed  PubMed Central  Google Scholar 

  102. Warren JW, Howard FM, Cross RK, Good JL, Weissman MM, Wesselmann U, Langenberg P, Greenberg P, Clauw DJ (2009) Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology 73:52–57. doi:10.1016/j.urology.2008.06.031

    Article  PubMed  Google Scholar 

  103. Novi JM, Jeronis S, Srinivas S, Srinivasan R, Morgan MA, Arya LA (2005) Risk of irritable bowel syndrome and depression in women with interstitial cystitis: a case-control study. J Urol 174:937–940. doi:10.1097/01.ju.0000169258.31345.5d

    Article  PubMed  Google Scholar 

  104. Laganà AS, La Rosa VL, Rapisarda AM, Vitale SG (2017) Comment on: “effect on sexual function of patients and patients’ spouses after midurethal sling procedure for stress urinary incontinence: a prospective single center study”. Low Urin Tract Symptoms 9:62. doi:10.1111/luts.12164

    Article  PubMed  Google Scholar 

  105. Gardella B, Porru D, Nappi RE, Dacco MD, Chiesa A, Spinillo A (2011) Interstitial cystitis is associated with vulvodynia and sexual dysfunction—a case-control study. J Sex Med 8:1726–1734. doi:10.1111/j.1743-6109.2011.02251.x

    Article  PubMed  Google Scholar 

  106. Carrico DJ, Sherer KL, Peters KM (2009) The relationship of interstitial cystitis/painful bladder syndrome to vulvodynia. Urol Nurs 29:233–238

    PubMed  Google Scholar 

  107. Tirlapur SA, Kuhrt K, Chaliha C, Ball E, Meads C, Khan KS (2013) The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis. Int J Surg 11:233–237. doi:10.1016/j.ijsu.2013.02.003

    Article  CAS  PubMed  Google Scholar 

  108. Pontari MA (2006) Chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: are they related? Curr Urol Rep 7:329–334. doi:10.1007/s11934-996-0013-1

    Article  PubMed  Google Scholar 

  109. Paulson JD, Delgado M (2005) Chronic pelvic pain: the occurrence of interstitial cystitis in a gynecological population. JSLS 9:426–430

    PubMed  PubMed Central  Google Scholar 

  110. Vitale SG, La Rosa VL, Rapisarda AM, Laganà AS (2016) Impact of endometriosis on quality of life and psychological well-being. J Psychosom Obstet Gynaecol. doi:10.1080/0167482X.2016.1244185

    Google Scholar 

  111. Vetvicka V, Laganà AS, Salmeri FM, Triolo O, Palmara VI, Vitale SG, Sofo V, Kralickova M (2016) Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives. Arch Gynecol Obstet 294:897–904. doi:10.1007/s00404-016-4195-6

    Article  CAS  PubMed  Google Scholar 

  112. Clemens JQ, Meenan RT, O’Keeffe Rosetti MC, Kimes TA, Calhoun EA (2008) Case-control study of medical comorbidities in women with interstitial cystitis. J Urol 179:2222–2225. doi:10.1016/j.juro.2008.01.172

    Article  PubMed  Google Scholar 

  113. Elliott CS, Payne CK (2012) Interstitial cystitis and the overlap with overactive bladder. Curr Urol Rep 13:319–326. doi:10.1007/s11934-012-0264-y

    Article  PubMed  Google Scholar 

  114. Chung MK, Butrick CW, Chung CW (2010) The overlap of interstitial cystitis/painful bladder syndrome and overactive bladder. JSLS 14:83–90. doi:10.4293/108680810X12674612014743

    Article  PubMed  PubMed Central  Google Scholar 

  115. Cameron AP, Gajewski JB (2009) Bladder outlet obstruction in painful bladder syndrome/interstitial cystitis. Neurourol Urodyn 28:944–948. doi:10.1002/nau.20729

    Article  PubMed  Google Scholar 

  116. Keller J, Chiou HY, Lin HC (2013) Increased risk of bladder cancer following diagnosis with bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 32:58–62. doi:10.1002/nau.22283

    Article  PubMed  Google Scholar 

  117. Vitale SG, Laganà AS, Gulino FA, Tropea A, Tarda S (2016) Prosthetic surgery versus native tissue repair of cystocele: literature review. Updates Surg 68:325–329. doi:10.1007/s13304-015-0343-y

    Article  PubMed  Google Scholar 

  118. Lembo F, Subba E, Laganà AS, Vitale SG, Valenti G, Magno C (2016) Intradiverticular Sarcomatoid Carcinoma of The Bladder: An Overview Starting From A Peculiar Case. Urol J 13:2800–2802

    PubMed  Google Scholar 

  119. Peeker R, Atanasiu L, Logadottir Y (2003) Intercurrent autoimmune conditions in classic and non-ulcer interstitial cystitis. Scand J Urol Nephrol 37:60–63. doi:10.1080/00365590310008721

    Article  PubMed  Google Scholar 

  120. Watkins KE, Eberhart N, Hilton L, Suttorp MJ, Hepner KA, Clemens JQ, Berry SH (2011) Depressive disorders and panic attacks in women with bladder pain syndrome/interstitial cystitis: a population-based sample. Gen Hosp Psychiatry 33:143–149. doi:10.1016/j.genhosppsych.2011.01.004

    Article  PubMed  PubMed Central  Google Scholar 

  121. Goldstein HB, Safaeian P, Garrod K, Finamore PS, Kellogg-Spadt S, Whitmore KE (2008) Depression, abuse and its relationship to interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct 19:1683–1686. doi:10.1007/s00192-008-0712-x

    Article  CAS  PubMed  Google Scholar 

  122. Clemens JQ, Brown SO, Calhoun EA (2008) Mental health diagnoses in patients with interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control study. J Urol 180:1378–1382. doi:10.1016/j.juro.2008.06.032

    Article  PubMed  PubMed Central  Google Scholar 

  123. Keller JJ, Liu SP, Lin HC (2013) Increased risk of depressive disorder following diagnosis with bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 32:467–471. doi:10.1002/nau.22316

    Article  PubMed  Google Scholar 

  124. Link CL, Pulliam SJ, Hanno PM, Hall SA, Eggers PW, Kusek JW, McKinlay JB (2008) Prevalence and psychosocial correlates of symptoms suggestive of painful bladder syndrome: results from the Boston area community health survey. J Urol 180:599–606. doi:10.1016/j.juro.2008.04.009

    Article  PubMed  PubMed Central  Google Scholar 

  125. Richter B, Hesse U, Hansen AB, Horn T, Mortensen SO, Nordling J (2010) Bladder pain syndrome/interstitial cystitis in a Danish population: a study using the 2008 criteria of the European Society for the Study of Interstitial Cystitis. BJU Int 105:660–667. doi:10.1111/j.1464-410X.2009.08847.x

    Article  PubMed  Google Scholar 

  126. Tsai CF, Ouyang WC, Tsai SJ, Hong CJ, Lin TL (2010) Risk factors for poor sleep quality among patients with interstitial cystitis in Taiwan. Neurourol Urodyn 29:568–572. doi:10.1002/nau.20799

    PubMed  Google Scholar 

  127. Kang JH, Keller JJ, Chen YK, Lin HC (2013) Reflux esophagitis increased the risk of bladder pain syndrome/interstitial cystitis: a 3-year follow-up study. Neurourol Urodyn 32:271–275. doi:10.1002/nau.22270

    Article  PubMed  Google Scholar 

  128. Chung SD, Xirasagar S, Lin CC, Ling W, Li HC, Lin HC (2015) Increased risk of ischemic stroke among women with bladder pain syndrome/interstitial cystitis: a cohort study from Taiwan. Neurourol Urodyn 34:44–49. doi:10.1002/nau.22515

    Article  PubMed  Google Scholar 

  129. Keller J, Chen YK, Lin HC (2013) Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study. Int Urogynecol J 24:565–571. doi:10.1007/s00192-012-1917-6

    Article  PubMed  Google Scholar 

  130. Gomes CM, Sanchez-Ortiz RF, Harris C, Wein AJ, Rovner ES (2001) Significance of hematuria in patients with interstitial cystitis: review of radiographic and endoscopic findings. Urology 57:262–265. doi:10.1016/s0090-4295(00)00918-3

    Article  CAS  PubMed  Google Scholar 

  131. Christmas TJ, Smith GL, Rode J (1996) Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis. Br J Urol 78:862–865. doi:10.1046/j.1464-410x.1996.02599.x

    Article  CAS  PubMed  Google Scholar 

  132. Denson MA, Griebling TL, Cohen MB, Kreder KJ (2000) Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis. J Urol 164:1908–1911. doi:10.1016/s0022-5347(05)66915-7

    Article  CAS  PubMed  Google Scholar 

  133. Erickson DR, Tomaszewski JE, Kunselman AR, Bentley CM, Peters KM, Rovner ES, Demers LM, Wheeler MA, Keay SK (2005) Do the National Institute of Diabetes and Digestive and Kidney Diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol 173:93–97. doi:10.1097/01.ju.0000146466.71311.ab

    Article  PubMed  Google Scholar 

  134. Erickson DR, Tomaszewski JE, Kunselman AR, Stetter CM, Peters KM, Rovner ES, Demers LM, Wheeler MA, Keay SK (2008) Urine markers do not predict biopsy findings or presence of bladder ulcers in interstitial cystitis/painful bladder syndrome. J Urol 179:1850–1856. doi:10.1016/j.juro.2008.01.047

    Article  PubMed  PubMed Central  Google Scholar 

  135. Tomaszewski JE, Landis JR, Russack V, Williams TM, Wang LP, Hardy C, Brensinger C, Matthews YL, Abele ST, Kusek JW, Nyberg LM; Interstitial Cystitis Database Study Group (2001) Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. Urology 57:67–81. doi:10.1016/s0090-4295(01)01166-9

    Article  CAS  PubMed  Google Scholar 

  136. Hossler FE, Monson FC (1995) Microvasculature of the rabbit urinary bladder. Anat Rec 243:438–448. doi:10.1002/ar.1092430406

    Article  CAS  PubMed  Google Scholar 

  137. Lewis SA (2000) Everything you wanted to know about the bladder epithelium but were afraid to ask. Am J Physiol Renal Physiol 278:F867–F874

    CAS  PubMed  Google Scholar 

  138. Andersson KE, McCloskey KD (2014) Lamina propria: the functional center of the bladder? Neurourol Urodyn 33:9–16. doi:10.1002/nau.22465

    Article  PubMed  Google Scholar 

  139. Johansson SL, Fall M (1990) Clinical features and spectrum of light microscopic changes in interstitial cystitis. J Urol 143:1118–1124

    CAS  PubMed  Google Scholar 

  140. Graham E, Chai TC (2006) Dysfunction of bladder urothelium and bladder urothelial cells in interstitial cystitis. Curr Urol Rep 7:440–446. doi:10.1007/s11934-006-0051-8

    Article  PubMed  Google Scholar 

  141. Lynes WL, Flynn SD, Shortliffe LD, Stamey TA (1990) The histology of interstitial cystitis. Am J Surg Pathol 14:969–976. doi:10.1097/00000478-199010000-00011

    Article  CAS  PubMed  Google Scholar 

  142. Horn T, Holm NR, Hald T (1998) Interstitial cystitis. Ultrastructural observations on detrusor smooth muscle cells. APMIS 106:909–916. doi:10.1111/j.1699-0463.1998.tb00238.x

    Article  CAS  PubMed  Google Scholar 

  143. Rosamilia A, Cann L, Dwyer P, Scurry J, Rogers P (1999) Bladder microvasculature in women with interstitial cystitis. J Urol 161:1865–1870. doi:10.1016/S0022-5347(05)68830-1

    Article  CAS  PubMed  Google Scholar 

  144. Parsons CL, Lilly JD, Stein P (1991) Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J Urol 145:732–735

    CAS  PubMed  Google Scholar 

  145. Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC (1995) Increased number of substance P positive nerve fibres in interstitial cystitis. Br J Urol 75(6):744–750. doi:10.1111/j.1464-410X.1995.tb07384.x

    Article  CAS  PubMed  Google Scholar 

  146. Esko JD, Kimata K, Lindahl U (2009) Proteoglycans and Sulfated Glycosaminoglycans. In: Varki A, Cummings RD, Esko JD et al. (eds) Essentials of Glycobiology, 2nd edn. Cold Spring Harbor, New York.

  147. Hurst RE, Moldwin RM, Mulholland SG (2007) Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis. Urology 69:17–23. doi:10.1016/j.urology.2006.03.083

    Article  PubMed  Google Scholar 

  148. Theoharides TC, Pang X, Letourneau R, Sant GR (1998) Interstitial cystitis: a neuroimmunoendocrine disorder. Ann N Y Acad Sci 840:619–634. doi:10.1111/j.1749-6632.1998.tb09601.x

    Article  CAS  PubMed  Google Scholar 

  149. Hurst RE, Zebrowski R (1994) Identification of proteoglycans present at high density on bovine and human bladder luminal surface. J Urol 152:1641–1645

    CAS  PubMed  Google Scholar 

  150. Richter B, Roslind A, Hesse U, Nordling J, Johansen JS, Horn T, Hansen AB (2010) YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis. Histopathology 57:371–383. doi:10.1111/j.1365-2559.2010.03640.x

    Article  PubMed  Google Scholar 

  151. Treutlein G, Dorsch R, Euler KN, Hauck SM, Amann B, Hartmann K, Deeg CA (2012) Novel potential interacting partners of fibronectin in spontaneous animal model of interstitial cystitis. PloS one 7:e51391. doi:10.1371/journal.pone.0051391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Lewis SA, Berg JR, Kleine TJ (1995) Modulation of epithelial permeability by extracellular macromolecules. Physiol Rev 75:561–589

    CAS  PubMed  Google Scholar 

  153. Acharya P, Beckel J, Ruiz WG, Wang E, Rojas R, Birder L, Apodaca G (2004) Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium. Am J Physiol Renal Physiol 287:F305-F318. doi:10.1152/ajprenal.00341.2003

    PubMed  Google Scholar 

  154. Pochynyuk O, Tong Q, Staruschenko A, Ma HP, Stockand JD (2006) Regulation of the epithelial Na + channel (ENaC) by phosphatidylinositides. Am J Physiol Renal Physiol 290:F949-F957. doi:10.1152/ajprenal.00386.2005

    PubMed  Google Scholar 

  155. Rubenwolf PC, Georgopoulos NT, Kirkwood LA, Baker SC, Southgate J (2012) Aquaporin expression contributes to human transurothelial permeability in vitro and is modulated by NaCl. PloS one 7:e45339. doi:10.1371/journal.pone.0045339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Shyr CR, Chen CC, Hsieh TF, Chang CH, Ma WL, Yeh S, Messing E, Li TH, Li FY, Chang C (2013) The expression and actions of androgen receptor in upper urinary tract urothelial carcinoma (UUTUC) tissues and the primary cultured cells. Endocr 43:191–199. doi:10.1007/s12020-012-9762-4

    Article  CAS  Google Scholar 

  157. Hanna-Mitchell AT, Beckel JM, Barbadora S, Kanai AJ, de Groat WC, Birder LA (2007) Non-neuronal acetylcholine and urinary bladder urothelium. Life Sci 80:2298–2302. doi:10.1016/j.lfs.2007.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Downie JW, Karmazyn M (1984) Mechanical trauma to bladder epithelium liberates prostanoids which modulate neurotransmission in rabbit detrusor muscle. J Pharmacol Exp Ther 230:445–449

    CAS  PubMed  Google Scholar 

  159. Fernandes VS, Hernandez M (2016) The role of nitric oxide and hydrogen sulfide in urinary tract function. Basic Clin Pharmacol Toxicol 119(Suppl 3):34–41. doi:10.1111/bcpt.12565

    Article  CAS  PubMed  Google Scholar 

  160. Nausch B, Heppner TJ, Nelson MT (2010) Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release. Am J Physiol Regul Integr Comp Physiol 299:R878–R888. doi:10.1152/ajpregu.00180.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Munoz A, Smith CP, Boone TB, Somogyi GT (2011) Overactive and underactive bladder dysfunction is reflected by alterations in urothelial ATP and NO release. Neurochem Int 58:295–300. doi:10.1016/j.neuint.2010.12.002

    Article  CAS  PubMed  Google Scholar 

  162. Tempest HV, Dixon AK, Turner WH, Elneil S, Sellers LA, Ferguson DR (2004) P2X and P2X receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int 93:1344–1348. doi:10.1111/j.1464-410X.2004.04858.x

    Article  CAS  PubMed  Google Scholar 

  163. Hwang P, Auclair B, Beechinor D, Diment M, Einarson TR (1997) Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a meta-analysis. Urology 50:39–43. doi:10.1016/S0090-4295(97)00110-6

    Article  CAS  PubMed  Google Scholar 

  164. Zhang W, Deng X, Liu C, Wang X (2016) Intravesical treatment for interstitial cystitis/painful bladder syndrome: a network meta-analysis. Int Urogynecol J. doi:10.1007/s00192-016-3079-4

    Google Scholar 

  165. Keay S, Schwalbe RS, Trifillis AL, Lovchik JC, Jacobs S, Warren JW (1995) A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology 45:223–229. doi:10.1016/0090-4295(95)80009-3

    Article  CAS  PubMed  Google Scholar 

  166. English SF, Liebert M, Cross CA, McGuire EJ (1998) The incidence of Helicobacter pylori in patients with interstitial cystitis. J Urol 159:772–773. doi:10.1016/S0022-5347(01)63725-X

    Article  CAS  PubMed  Google Scholar 

  167. Warren JW (1994) Is interstitial cystitis an infectious disease? Med Hypotheses 43:183–186. doi:10.1016/0306-9877(94)90150-3

    Article  CAS  PubMed  Google Scholar 

  168. Heritz DM, Lacroix JM, Batra SD, Jarvi KA, Beheshti B, Mittelman MW (1997) Detection of eubacteria in interstitial cystitis by 16 S rDNA amplification. J Urol 158:2291–2295. doi:10.1016/S0022-5347(01)68237-5

    Article  CAS  PubMed  Google Scholar 

  169. Winnard KP, Dmitrieva N, Berkley KJ (2006) Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve. Am J Physiol Regul Integr Comp Physiol 291:R1592–R1601. doi:10.1152/ajpregu.00455.2006

    Article  CAS  PubMed  Google Scholar 

  170. Atug F, Turkeri L, Atug O, Cal C (2004) Detection of Helicobacter pylori in bladder biopsy specimens of patients with interstitial cystitis by polymerase chain reaction. Urol Res 32:346–349. doi:10.1007/s00240-004-0425-7

    Article  CAS  PubMed  Google Scholar 

  171. Agarwal M, Dixon RA (2003) A study to detect Helicobacter pylori in fresh and archival specimens from patients with interstitial cystitis, using amplification methods. BJU Int 91:814–816. doi:10.1046/j.1464-410X.2003.04221.x

    Article  CAS  PubMed  Google Scholar 

  172. Zhang QH, Shen XC, Zhou ZS, Chen ZW, Lu GS, Song B (2010) Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment. Int Urogynecol J 21:103–109. doi:10.1007/s00192-009-0994-7

    Article  PubMed  Google Scholar 

  173. Al-Hadithi HN, Williams H, Hart CA, Frazer M, Adams EJ, Richmond DH, Tincello DG (2005) Absence of bacterial and viral DNA in bladder biopsies from patients with interstitial cystitis/chronic pelvic pain syndrome. J Urol 174(1):151–154. doi:10.1097/01.ju.0000161605.14804.a9

    Article  CAS  PubMed  Google Scholar 

  174. Duncan JL, Schaeffer AJ (1997) Do infectious agents cause interstitial cystitis? Urology 49:48–51. doi:10.1016/S0090-4295(99)80331-8

    Article  CAS  PubMed  Google Scholar 

  175. Haarala M, Jalava J, Laato M, Kiilholma P, Nurmi M, Alanen A (1996) Absence of bacterial DNA in the bladder of patients with interstitial cystitis. J Urol 156:1843–1845. doi:10.1016/S0022-5347(01)65549-6

    Article  CAS  PubMed  Google Scholar 

  176. Haq A, Mattocks S, Wong L, Dasgupta P, Dawson C, Blackford HN, Sharma S, Turner AG (2001) Incidence of Helicobacter pylori in patients with interstitial cystitis. Eur Urol 40:652–654. doi:10.1159/000049852

    Article  CAS  PubMed  Google Scholar 

  177. Sant GR, Kempuraj D, Marchand JE, Theoharides TC (2007) The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology 69:34–40. doi:10.1016/j.urology.2006.08.1109

    Article  PubMed  Google Scholar 

  178. Galli SJ, Nakae S, Tsai M (2005) Mast cells in the development of adaptive immune responses. Nat Immunol 6:135–142. doi:10.1038/ni1158

    Article  CAS  PubMed  Google Scholar 

  179. Galli SJ, Maurer M, Lantz CS (1999) Mast cells as sentinels of innate immunity. Curr Opin Immunol 11:53–59. doi:10.1016/S0952-7915(99)80010-7

    Article  CAS  PubMed  Google Scholar 

  180. Metz M, Maurer M (2007) Mast cells-key effector cells in immune responses. Trends Immunol 28:234–241. doi:10.1016/j.it.2007.03.003

    Article  CAS  PubMed  Google Scholar 

  181. Simmons JL, Bunce PL (1958) On the use of an antihistamine in the treatment of interstitial cystitis. Am Surg 24:664–667

    CAS  PubMed  Google Scholar 

  182. Lynes WL, Flynn SD, Shortliffe LD, Lemmers M, Zipser R, Roberts LJ 2nd, Stamey TA (1987) Mast cell involvement in interstitial cystitis. J Urol 138:746–752

    CAS  PubMed  Google Scholar 

  183. Sant GR, Theoharides TC (1996) Re: Mast cell counts are not useful in the diagnosis of nonulcerative interstitial cystitis. J Urol 156:1445–1446. doi:10.1016/S0022-5347(01)65619-2

    Article  CAS  PubMed  Google Scholar 

  184. Dodd LG, Tello J (1998) Cytologic examination of urine from patients with interstitial cystitis. Acta Cytol 42:923–927. doi:10.1159/000331969

    Article  CAS  PubMed  Google Scholar 

  185. Anderson JB, Parivar F, Lee G, Wallington TB, MacIver AG, Bradbrook RA, Gingell JC (1989) The enigma of interstitial cystitis—an autoimmune disease? Br J Urol 63:58–63. doi:10.1111/j.1464-410X.1989.tb05124.x

    Article  CAS  PubMed  Google Scholar 

  186. Reichlin S (1993) Neuroendocrine-immune interactions. N Engl J Med 329:1246–1253. doi:10.1056/NEJM199310213291708

    Article  CAS  PubMed  Google Scholar 

  187. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638

    CAS  PubMed  Google Scholar 

  188. Gaillard RC (1994) Neuroendocrine-immune system interactions The immune-hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 5:303–309. doi:10.1016/1043-2760(94)P3206-M

    Article  CAS  PubMed  Google Scholar 

  189. Mulla A, Buckingham JC (1999) Regulation of the hypothalamo-pituitary-adrenal axis by cytokines. Baillieres. Best Pract Res Clin Endocrinol Metab 13:503–521. doi:10.1053/beem.1999.0041

    Article  CAS  Google Scholar 

  190. Webster JI, Tonelli L, Sternberg EM (2002) Neuroendocrine regulation of immunity. Annu Rev Immunol 20:125–163. doi:10.1146/annurev.immunol.20.082401.104914

    Article  CAS  PubMed  Google Scholar 

  191. Keay S (2008) Cell signaling in interstitial cystitis/painful bladder syndrome. Cell Signal 20:2174–2179. doi:10.1016/j.cellsig.2008.06.004

    Article  CAS  PubMed  Google Scholar 

  192. Buffington CA, Teng B, Somogyi GT (2002) Norepinephrine content and adrenoceptor function in the bladder of cats with feline interstitial cystitis. J Urol 167:1876–1880. doi:10.1016/S0022-5347(05)65253-6

    Article  CAS  PubMed  Google Scholar 

  193. Reche Junior A, Buffington CA (1998) Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus of cats with interstitial cystitis. J Urol 159:1045–1048

    Article  CAS  PubMed  Google Scholar 

  194. Westropp JL, Kass PH, Buffington CA (2006) Evaluation of the effects of stress in cats with idiopathic cystitis. Am J Vet Res 67:731–736. doi:10.2460/ajvr.67.4.731

    Article  PubMed  Google Scholar 

  195. Nazif O, Teichman JM, Gebhart GF (2007) Neural upregulation in interstitial cystitis. Urology 69:24–33. doi:10.1016/j.urology.2006.08.1108

    Article  PubMed  Google Scholar 

  196. Buffington CA, Pacak K (2001) Increased plasma norepinephrine concentration in cats with interstitial cystitis. J Urol 165:2051–2054. doi:10.1016/S0022-5347(05)66292-1

    Article  CAS  PubMed  Google Scholar 

  197. Dimitrakov J, Tchitalov J, Zlatanov T, Dikov D, Rawadi G (2001) Corticotropin-releasing hormone perturbations in interstitial cystitis patients: evidence for abnormal sympathetic activity. Urology 57:128. doi:10.1016/S0090-4295(01)01098-6

    Article  CAS  PubMed  Google Scholar 

  198. Westropp JL, Welk KA, Buffington CA (2003) Small adrenal glands in cats with feline interstitial cystitis. J Urol 170:2494–2497. doi:10.1097/01.ju.0000095566.63870.66

    Article  PubMed  Google Scholar 

  199. Stein PC, Torri A, Parsons CL (1999) Elevated urinary norepinephrine in interstitial cystitis. Urology 53:1140–1143. doi:10.1016/S0090-4295(98)00663-3

    Article  CAS  PubMed  Google Scholar 

  200. Lutgendorf SK, Kreder KJ, Rothrock NE, Hoffman A, Kirschbaum C, Sternberg EM, Zimmerman MB, Ratliff TL (2002) Diurnal cortisol variations and symptoms in patients with interstitial cystitis. J Urol 167:1338–1343. doi:10.1016/S0022-5347(05)65295-0

    Article  PubMed  Google Scholar 

  201. Heim C, Ehlert U, Hellhammer DH (2000) The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25:1–35. doi:10.1016/S0306-4530(99)00035-9

    Article  CAS  PubMed  Google Scholar 

  202. Parsons CL (2007) The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology 69:9–16. doi:10.1016/j.urology.2006.03.084

    Article  PubMed  Google Scholar 

  203. Steers WD, Kolbeck S, Creedon D, Tuttle JB (1991) Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest 88:1709–1715. doi:10.1172/JCI115488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Liu HT, Tyagi P, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int 104:1476–1481. doi:10.1111/j.1464-410X.2009.08675.x

    Article  CAS  PubMed  Google Scholar 

  205. Hanno P, Andersson KE, Birder L, Elneil S, Kanai A, Pontari M (2012) Chronic pelvic pain syndrome/bladder pain syndrome: taking stock, looking ahead: ICI-RS 2011. Neurourol Urodyn 31:375–383. doi:10.1002/nau.22202

    Article  PubMed  Google Scholar 

  206. Amaya F, Oh-hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G, Tominaga M, Tanaka Y, Tanaka M (2003) Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 963:190–196. doi:10.1016/S0006-8993(02)03972-0

    Article  CAS  PubMed  Google Scholar 

  207. Liu BL, Yang F, Zhan HL, Feng ZY, Zhang ZG, Li WB, Zhou XF (2014) Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome. Urol Int 92:202–208. doi:10.1159/000355175

    Article  CAS  PubMed  Google Scholar 

  208. Grover S, Srivastava A, Lee R, Tewari AK, Te AE (2011) Role of inflammation in bladder function and interstitial cystitis. Ther Adv Urol 3:19–33. doi:10.1177/1756287211398255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Offiah I, Didangelos A, Dawes J, Cartwright R, Khullar V, Bradbury EJ, O’Sullivan S, Williams D, Chessell IP, Pallas K, Graham G, O’Reilly BA, McMahon SB (2016) The Expression of Inflammatory Mediators in Bladder Pain Syndrome. Eur Urol 70:283–290. doi:10.1016/j.eururo.2016.02.058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Tsai MH, Kamm KE, Stull JT (2012) Signalling to contractile proteins by muscarinic and purinergic pathways in neurally stimulated bladder smooth muscle. J Physiol 590:5107–5121. doi:10.1113/jphysiol.2012.235424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Nasrin S, Masuda E, Kugaya H, Ito Y, Yamada S (2013) Improvement by phytotherapeutic agent of detrusor overactivity, down-regulation of pharmacological receptors and urinary cytokines in rats with cyclophosphamide induced cystitis. J Urol 189:1123–1129. doi:10.1016/j.juro.2012.09.054

    Article  CAS  PubMed  Google Scholar 

  212. Sun Y, Chai TC (2004) Up-regulation of P2 × 3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171:448–452. doi:10.1097/01.ju.0000099660.46774.3c

    Article  CAS  PubMed  Google Scholar 

  213. Yang W, Rudick CN, Hoxha E, Allsop SA, Dimitrakoff JD, Klumpp DJ (2012) Ca(2+)/calmodulin-dependent protein kinase II is associated with pelvic pain of neurogenic cystitis. Am J Physiol Renal Physiol 303:F350-F356. doi:10.1152/ajprenal.00077.2012

    Google Scholar 

  214. Westropp JL, Buffington CA (2002) In vivo models of interstitial cystitis. J Urol 167:694–702. doi:10.1016/S0022-5347(01)69129-8

    Article  PubMed  Google Scholar 

  215. Clasper M (1990) A case of interstitial cystitis and Hunner’s ulcer in a domestic shorthaired cat. N Z Vet J 38:158–160. doi:10.1080/00480169.1990.35644

    Article  CAS  PubMed  Google Scholar 

  216. Buffington CA (2011) Idiopathic cystitis in domestic cats–beyond the lower urinary tract. J Vet Intern Med 25:784–796. doi:10.1111/j.1939-1676.2011.0732.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Kruger JM, Osborne CA, Lulich JP (2009) Changing paradigms of feline idiopathic cystitis. Vet Clin North Am Small Anim Pract 39:15–40. doi:10.1016/j.cvsm.2008.09.008

    Article  PubMed  Google Scholar 

  218. Birder LA, Ruan HZ, Chopra B, Xiang Z, Barrick S, Buffington CA, Roppolo JR, Ford AP, de Groat WC, Burnstock G (2004) Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am J Physiol Renal Physiol 287:F1084–F1091. doi:10.1152/ajprenal.00118.2004

    Article  CAS  PubMed  Google Scholar 

  219. Elbadawi AE, Light JK (1996) Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new observations and their potential significance in pathogenesis. Urol Int 56:137–162. doi:10.1159/000282832

    Article  CAS  PubMed  Google Scholar 

  220. Rivas DA, Chancellor MB, Shupp-Byrne S, Shenot PJ, McHugh K, McCue P (1997) Molecular marker for development of interstitial cystitis in rat model: isoactin gene expression. J Urol 157(5):1937–1940. doi:10.1016/S0022-5347(01)64905-X

    Article  CAS  PubMed  Google Scholar 

  221. McCarthy LS, Smeulders N, Wilcox DT (2003) Cell biology of bladder development and the role of the extracellular matrix. Nephron Exp Nephrol 95:e129–e133. doi:10.1159/000074839

    Article  CAS  PubMed  Google Scholar 

  222. Herz DB, Aitken K, Bagli DJ (2003) Collagen directly stimulates bladder smooth muscle cell growth in vitro: regulation by extracellular regulated mitogen activated protein kinase. J Urol 170:2072–2076. doi:10.1097/01.ju.0000091810.33953.13

    Article  CAS  PubMed  Google Scholar 

  223. Upadhyay J, Aitken KJ, Damdar C, Bolduc S, Bagli DJ (2003) Integrins expressed with bladder extracellular matrix after stretch injury in vivo mediate bladder smooth muscle cell growth in vitro. J Urol 169:750–755. doi:10.1097/01.ju.0000051682.61041.a5

    Article  CAS  PubMed  Google Scholar 

  224. Aitken KJ, Bagli DJ (2009) The bladder extracellular matrix. Part I: architecture, development and disease. Nat Rev Urol 6:596–611. doi:10.1038/nrurol.2009.201

    Article  CAS  PubMed  Google Scholar 

  225. Neuhaus J, Schwalenberg T, Horn LC, Alexander H, Stolzenburg JU (2011) New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis. Adv Urol 2011:639479. doi:10.1155/2011/639479

    Article  PubMed  PubMed Central  Google Scholar 

  226. Warren JW, Jackson TL, Langenberg P, Meyers DJ, Xu J (2004) Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis. Urology 63:17–21. doi:10.1016/j.urology.2003.08.027

    Article  PubMed  Google Scholar 

  227. Warren JW, Keay SK, Meyers D, Xu J (2001) Concordance of interstitial cystitis in monozygotic and dizygotic twin pairs. Urology 57:22–25. doi:10.1016/S0090-4295(01)01120-7

    Article  CAS  PubMed  Google Scholar 

  228. Altman D, Lundholm C, Milsom I, Peeker R, Fall M, Iliadou AN, Pedersen NL (2011) The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample. Eur Urol 59:280–285. doi:10.1016/j.eururo.2010.10.028

    Article  PubMed  Google Scholar 

  229. Li GZ, Zhang N, Du P, Yang Y, Wu SL, Xiao YX, Jin R, Liu L, Shen H, Dai Y (2010) Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med J (Engl) 123:2842–2846

    Google Scholar 

  230. Friedlander JI, Shorter B, Moldwin RM (2012) Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions. BJU Int 109:1584–1591. doi:10.1111/j.1464-410X.2011.10860.x

    Article  PubMed  Google Scholar 

  231. Schaeffer AJ, Freeman M, Giambarresi L (2010) Introduction to the national urology research agenda: a roadmap for priorities in urological disease research. J Urol 184:823–824. doi:10.1016/j.juro.2010.06.046

    Article  PubMed  Google Scholar 

  232. Doggweiler-Wiygul R, Blankenship J, MacDiarmid SA (2000) Interstitial cystitis: the painful bladder syndrome. Curr Rev. Pain 4:137–141

    CAS  Google Scholar 

  233. Payne CK, Terai A, Komatsu K (2003) Research criteria versus clinical criteria for interstitial cystitis. Int J Urol 10 Suppl:S7-S10. doi:10.1046/j.1442-2042.10.s1.3.x

    PubMed  Google Scholar 

  234. Ratner V (2001) Current controversies that adversely affect interstitial cystitis patients. Urology 57:89–94. doi:10.1016/S0090-4295(01)01132-3

    Article  CAS  PubMed  Google Scholar 

  235. Evans RJ, Sant GR (2007) Current diagnosis of interstitial cystitis: an evolving paradigm. Urology 69:64–72. doi:10.1016/j.urology.2006.05.048

    Article  PubMed  Google Scholar 

  236. Berry SH, Bogart LM, Pham C, Liu K, Nyberg L, Stoto M, Suttorp M, Clemens JQ (2010) Development, validation and testing of an epidemiological case definition of interstitial cystitis/painful bladder syndrome. J Urol 183:1848–1852. doi:10.1016/j.juro.2009.12.103

    Article  PubMed  PubMed Central  Google Scholar 

  237. u Zhang CO, Li ZL, Shoenfelt JL, Kong CZ, Chai TC, Erickson DR, Peters KM, Rovner ES, Keay S (2003) Comparison of APF activity and epithelial growth factor levels in urine from Chinese, African-American, and white American patients with interstitial cystitis. Urology 61:897–901. doi:10.1016/S0090-4295(02)02597-9

    Article  PubMed  Google Scholar 

  238. Rashid HH, Reeder JE, O’Connell MJ, Zhang CO, Messing EM, Keay SK (2004) Interstitial cystitis antiproliferative factor (APF) as a cell-cycle modulator. BMC Urol 4:3. doi:10.1186/1471-2490-4-3

    Article  PubMed  PubMed Central  Google Scholar 

  239. Keay S, Zhang CO, Marvel R, Chai T (2001) Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor: sensitive and specific urine markers for interstitial cystitis. Urology 57:104. doi:10.1016/S0090-4295(01)01028-7

    Article  CAS  PubMed  Google Scholar 

  240. Keay S, Warren JW (1998) A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair. Med Hypotheses 51:79–83. doi:10.1016/S0306-9877(98)90260-2

    Article  CAS  PubMed  Google Scholar 

  241. Kim J, Freeman MR (2011) Antiproliferative factor signaling and interstitial cystitis/painful bladder syndrome. Int Neurourol J 15:184–191. doi:10.5213/inj.2011.15.4.184

    Article  PubMed  PubMed Central  Google Scholar 

  242. Li Z, Zhu Y, Yu M, Ji D, Yang Z, Kong C (2013) c-Jun is involved in interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human bladder cancer T24 cells. Urol Oncol 31:228–233. doi:10.1016/j.urolonc.2010.11.011

    Article  PubMed  CAS  Google Scholar 

  243. Kaczmarek P, Tocci GM, Keay SK, Adams KM, Zhang CO, Koch KR, Grkovic D, Guo L, Michejda CJ, Barchi JJ, Jr. (2010) Structure-activity studies on antiproliferative factor (APF) glycooctapeptide derivatives. ACS Med Chem Lett 1:390–394. doi:10.1021/ml100087a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Kim J, Keay SK, Dimitrakov JD, Freeman MR (2007) p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells. FEBS Lett 581:3795–3799. doi:10.1016/j.febslet.2007.06.058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Kuo HC (2014) Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis. Int J Urol 21(Suppl 1):34–41. doi:10.1111/iju.12311

    Article  PubMed  Google Scholar 

  246. Steers WD, Tuttle JB (2006) Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol 3:101–110. doi:10.1038/ncpuro0408

    Article  CAS  PubMed  Google Scholar 

  247. Ochodnicky P, Cruz CD, Yoshimura N, Michel MC (2011) Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target. Neurourol Urodyn 30:1227–1241. doi:10.1002/nau.21022

    CAS  PubMed  Google Scholar 

  248. Gonzalez EJ, Arms L, Vizzard MA (2014) The role(s) of cytokines/chemokines in urinary bladder inflammation and dysfunction. Biomed Res Int 2014:120525. doi:10.1155/2014/120525

    PubMed  PubMed Central  Google Scholar 

  249. Rooney P, Srivastava A, Watson L, Quinlan LR, Pandit A (2015) Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis. Acta Biomater 19:66–75. doi:10.1016/j.actbio.2015.02.030

    Article  CAS  PubMed  Google Scholar 

  250. Jiang YH, Peng CH, Liu HT, Kuo HC (2013) Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis/bladder pain syndrome. PloS one 8:e76779. doi:10.1371/journal.pone.0076779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Lotz M, Villiger P, Hugli T, Koziol J, Zuraw BL (1994) Interleukin-6 and interstitial cystitis. J Urol 152:869–873

    CAS  PubMed  Google Scholar 

  252. Erickson DR, Xie SX, Bhavanandan VP, Wheeler MA, Hurst RE, Demers LM, Kushner L, Keay SK (2002) A comparison of multiple urine markers for interstitial cystitis. J Urol 167:2461–2469. doi:10.1016/S0022-5347(05)65005-7

    Article  CAS  PubMed  Google Scholar 

  253. Tyagi P, Killinger K, Tyagi V, Nirmal J, Chancellor M, Peters KM (2012) Urinary chemokines as noninvasive predictors of ulcerative interstitial cystitis. J Urol 187:2243–2248. doi:10.1016/j.juro.2012.01.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Lokeshwar VB, Selzer MG, Cerwinka WH, Gomez MF, Kester RR, Bejany DE, Gousse AE (2005) Urinary uronate and sulfated glycosaminoglycan levels: markers for interstitial cystitis severity. J Urol 174:344–349. doi:10.1097/01.ju.0000161599.69942.2e

    Article  CAS  PubMed  Google Scholar 

  255. Shrom SH, Parsons CL, Mulholland SG (1977) Role of urothelial surface mucoprotein in intrinsic bladder defense. Urology 9:526–533. doi:10.1016/0090-4295(77)90245-X

    Article  CAS  PubMed  Google Scholar 

  256. Hauser PJ, Dozmorov MG, Bane BL, Slobodov G, Culkin DJ, Hurst RE (2008) Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis. J Urol 179:764–769. doi:10.1016/j.juro.2007.09.022

    Article  CAS  PubMed  Google Scholar 

  257. Argade S, Chermansky C, Tyagi P (2016) Biomarkers for interstitial cystitis/painful bladder syndrome. Womens Health (Lond) 12:87–90. doi:10.2217/whe.15.93

    CAS  Google Scholar 

  258. Fowler JE Jr, Lynes WL, Lau JL, Ghosh L, Mounzer A (1988) Interstitial cystitis is associated with intraurothelial Tamm-Horsfall protein. J Urol 140:1385–1389

    PubMed  Google Scholar 

  259. Parsons CL, Stein P, Zupkas P, Chenoweth M, Argade SP, Proctor JG, Datta A, Trotter RN (2007) Defective Tamm-Horsfall protein in patients with interstitial cystitis. J Urol 178:2665–2670. doi:10.1016/j.juro.2007.07.125

    Article  CAS  PubMed  Google Scholar 

  260. Argade SP, Vanichsarn C, Chenoweth M, Parsons CL (2009) Abnormal glycosylation of Tamm-Horsfall protein in patients with interstitial cystitis. BJU Int 103:1085–1089. doi:10.1111/j.1464-410X.2008.08163.x

    Article  CAS  PubMed  Google Scholar 

  261. Marentette JO, Hurst RE, McHowat J (2015) Impaired Expression of prostaglandin E2 (PGE2) synthesis and degradation enzymes during differentiation of immortalized urothelial cells from patients with interstitial cystitis/painful bladder syndrome. PloS One 10:e0129466. doi:10.1371/journal.pone.0129466

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  262. Wada N, Ameda K, Furuno T, Okada H, Date I, Kakizaki H (2015) Evaluation of prostaglandin E2 and E-series prostaglandin receptor in patients with interstitial cystitis. J Urol 193:1987–1993. doi:10.1016/j.juro.2015.01.010

    Article  CAS  PubMed  Google Scholar 

  263. Koskela LR, Thiel T, Ehren I, De Verdier PJ, Wiklund NP (2008) Localization and expression of inducible nitric oxide synthase in biopsies from patients with interstitial cystitis. J Urol 180:737–741. doi:10.1016/j.juro.2008.03.184

    Article  CAS  PubMed  Google Scholar 

  264. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867. doi:10.1074/mcp.A300001-MCP200

    Article  CAS  PubMed  Google Scholar 

  265. Adachi J, Kumar C, Zhang Y, Olsen JV, Mann M (2006) The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins. Genome Biol 7:R80. doi:10.1186/gb-2006-7-9-R80

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  266. Goo YA, Tsai YS, Liu AY, Goodlett DR, Yang CC (2010) Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome: a pilot study. Int Braz J Urol 36:464–479. doi:10.1590/S1677-55382010000400010

    Article  PubMed  Google Scholar 

  267. Canter MP, Graham CA, Heit MH, Blackwell LS, Wilkey DW, Klein JB, Merchant ML (2008) Proteomic techniques identify urine proteins that differentiate patients with interstitial cystitis from asymptomatic control subjects. Am J Obstet Gynecol 198 (5):553 e551–556. doi:10.1016/j.ajog.2008.01.052

    Google Scholar 

  268. Song M, Lim J, Yu HY, Park J, Chun JY, Jeong J, Heo J, Kang H, Kim Y, Cho YM, Kim SW, Oh W, Choi SJ, Jang SW, Park S, Shin DM, Choo MS (2015) Mesenchymal stem cell therapy alleviates interstitial cystitis by activating Wnt signaling pathway. Stem Cells Dev 24:1648–1657. doi:10.1089/scd.2014.0459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Warren JW, van de Merwe JP, Nickel JC (2011) Interstitial cystitis/bladder pain syndrome and nonbladder syndromes: facts and hypotheses. Urology 78:727–732. doi:10.1016/j.urology.2011.06.014

    Article  PubMed  Google Scholar 

  270. Rudick CN, Chen MC, Mongiu AK, Klumpp DJ (2007) Organ cross talk modulates pelvic pain. Am J Physiol Regul Integr Comp Physiol 293:R1191–R1198. doi:10.1152/ajpregu.00411.2007

    Article  CAS  PubMed  Google Scholar 

  271. Minagawa T, Wyndaele M, Aizawa N, Igawa Y, Wyndaele JJ (2013) Mechanisms of pelvic organ cross-talk: 2. Impact of colorectal distention on afferent nerve activity of the rat bladder. J Urol 190:1123–1130. doi:10.1016/j.juro.2013.03.079

    Article  PubMed  Google Scholar 

  272. Peng HY, Chen GD, Lai CY, Hsieh MC, Hsu HH, Wu HC, Lin TB (2010) PI3K modulates estrogen-dependent facilitation of colon-to-urethra cross-organ reflex sensitization in ovariectomized female rats. J Neurochem 113:54–66. doi:10.1111/j.1471-4159.2010.06577.x

    Article  CAS  PubMed  Google Scholar 

  273. Acar D, Cayan S, Aktas S, Tek M, Akbay E (2007) The effect of tamoxifen on bladder functions and histology, and the role of estrogen receptor beta in a rat chemical cystitis model. Neurourol Urodyn 26:309–316. doi:10.1002/nau.20247

    Article  CAS  PubMed  Google Scholar 

  274. Cabral CA, Sampaio FJ, Cardoso LE (2003) Analysis of the modifications in the composition of bladder glycosaminoglycan and collagen as a consequence of changes in sex hormones associated with puberty or oophorectomy in female rats. J Urol 170:2512–2516. doi:10.1097/01.ju.0000088776.17126.93

    Article  CAS  PubMed  Google Scholar 

  275. Portman DJ, Gass ML, Vulvovaginal Atrophy Terminology Consensus Conference Panel (2014) Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Menopause 21:1063–1068. doi:10.1097/GME.0000000000000329

    Article  PubMed  Google Scholar 

  276. Nappi RE, Davis SR (2012) The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI. Climacteric 15:267–274. doi:10.3109/13697137.2012.657589

    Article  CAS  PubMed  Google Scholar 

  277. Novicki DE, Larson TR, Swanson SK (1998) Interstitial cystitis in men. Urology 52:621–624. doi:10.1016/S0090-4295(98)00317-3

    Article  CAS  PubMed  Google Scholar 

  278. Langenberg PW, Wallach EE, Clauw DJ, Howard FM, Diggs CM, Wesselmann U, Greenberg P, Warren JW (2010) Pelvic pain and surgeries in women before interstitial cystitis/painful bladder syndrome. Am J Obstet Gynecol 202(286):e281–e286. doi:10.1016/j.ajog.2009.10.866

    Google Scholar 

  279. Lemack GE, Zimmern PE (2001) Interstitial cystitis: reevaluation of patients who do no respond to standard treatments. Prog Urol 11:239–244

    CAS  PubMed  Google Scholar 

  280. Teichman JM, Nielsen-Omeis BJ, McIver BD (1997) Modified urodynamics for interstitial cystitis. Tech Urol 3:65–68

    CAS  PubMed  Google Scholar 

  281. Wu CH, Buffington CA, Fraser MO, Westropp JL (2011) Urodynamic evaluation of female cats with idiopathic cystitis. Am J Vet Res 72:578–582. doi:10.2460/ajvr.72.4.578

    Article  PubMed  PubMed Central  Google Scholar 

  282. Warren JW, Clauw DJ, Wesselmann U, Langenberg PW, Howard FM, Morozov V (2011) Sexuality and reproductive risk factors for interstitial cystitis/painful bladder syndrome in women. Urology 77:570–575. doi:10.1016/j.urology.2010.10.018

    Article  PubMed  Google Scholar 

  283. Rais-Bahrami S, Friedlander JI, Herati AS, Sadek MA, Ruzimovsky M, Moldwin RM (2012) Symptom profile variability of interstitial cystitis/painful bladder syndrome by age. BJU Int 109:1356–1359. doi:10.1111/j.1464-410X.2011.10481.x

    Article  PubMed  Google Scholar 

  284. Logadottir Y, Fall M, Kabjorn-Gustafsson C, Peeker R (2012) Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis. Scand J Urol Nephrol 46:365–370. doi:10.3109/00365599.2012.689008

    Article  PubMed  Google Scholar 

  285. Park JM (2001) Is interstitial cystitis an underdiagnosed problem in children? A diagnostic and therapeutic dilemma. Urology 57:30–31. doi:10.1016/S0090-4295(01)01122-0

    Article  CAS  PubMed  Google Scholar 

  286. Close CE, Carr MC, Burns MW, Miller JL, Bavendam TG, Mayo ME, Mitchell ME (1996) Interstitial cystitis in children. J Urol 156:860–862. doi:10.1016/S0022-5347(01)65842-7

    Article  CAS  PubMed  Google Scholar 

  287. Suskind AM, Berry SH, Ewing BA, Elliott MN, Suttorp MJ, Clemens JQ (2013) The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. J Urol 189:141–145. doi:10.1016/j.juro.2012.08.088

    Article  PubMed  Google Scholar 

  288. Hall SA, Link CL, Pulliam SJ, Hanno PM, Eggers PW, Kusek JW, McKinlay JB (2008) The relationship of common medical conditions and medication use with symptoms of painful bladder syndrome: results from the Boston area community health survey. J Urol 180:593–598. doi:10.1016/j.juro.2008.04.002

    Article  PubMed  Google Scholar 

  289. Payne CK, Joyce GF, Wise M, Clemens JQ, Urologic Diseases in America P (2007) Interstitial cystitis and painful bladder syndrome. J Urol 177:2042–2049. doi:10.1016/j.juro.2007.01.124

    Article  PubMed  Google Scholar 

  290. Tripp DA, Nickel JC, Wong J, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J (2012) Mapping of pain phenotypes in female patients with bladder pain syndrome/interstitial cystitis and controls. Eur Urol 62:1188–1194. doi:10.1016/j.eururo.2012.05.023

    Article  PubMed  Google Scholar 

  291. Erickson DR, Simon LJ, Belchis DA (1994) Relationships between bladder inflammation and other clinical features in interstitial cystitis. Urology 44:655–659. doi:10.1016/S0090-4295(94)80199-1

    Article  CAS  PubMed  Google Scholar 

  292. Cheng L, Davison DD, Adams J, Lopez-Beltran A, Wang L, Montironi R, Zhang S (2014) Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hematol 89:73–111. doi:10.1016/j.critrevonc.2013.08.008

    Article  PubMed  Google Scholar 

  293. Brenton JD, Carey LA, Ahmed AA, Caldas C (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23:7350–7360. doi:10.1200/JCO.2005.03.3845

    Article  CAS  PubMed  Google Scholar 

  294. Rakha EA, Reis-Filho JS, Ellis IO (2010) Combinatorial biomarker expression in breast cancer. Breast Cancer Res Treat 120:293–308. doi:10.1007/s10549-010-0746-x

    Article  CAS  PubMed  Google Scholar 

  295. Wessels LF, van Welsem T, Hart AA, van’t Veer LJ, Reinders MJ, Nederlof PM (2002) Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors. Cancer Res 62:7110–7117

    CAS  PubMed  Google Scholar 

  296. Covell DG, Wallqvist A, Rabow AA, Thanki N (2003) Molecular classification of cancer: unsupervised self-organizing map analysis of gene expression microarray data. Mol Cancer Ther 2:317–332

    CAS  PubMed  Google Scholar 

  297. Dolled-Filhart M, Ryden L, Cregger M, Jirstrom K, Harigopal M, Camp RL, Rimm DL (2006) Classification of breast cancer using genetic algorithms and tissue microarrays. Clin Cancer Res 12:6459–6468. doi:10.1158/1078-0432.CCR-06-1383

    Article  CAS  PubMed  Google Scholar 

  298. Andre F, Pusztai L (2006) Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy. Nat Clin Pract Oncol 3:621–632. doi:10.1038/ncponc0636

    Article  PubMed  Google Scholar 

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Author contributions

SSP manuscript writing, ASL manuscript writing, SGV manuscript editing, SB literature screening and data selection, MN manuscript writing, SG manuscript editing, GV literature screening and data selection, AMCR literature screening and data selection, VLLR manuscript editing, CM literature screening and data selection, OT manuscript writing, VD project supervision and final approval.

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Authors and Affiliations

  1. Department of Mechanical Engineering, University of Texas at San Antonio, San Antonio, TX, USA

    Sourav Sanchit Patnaik

  2. Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy

    Antonio Simone Laganà, Salvatore Giovanni Vitale & Onofrio Triolo

  3. Unit of Urology, Department of Human Pathology, University of Messina, Messina, Italy

    Salvatore Butticè & Carlo Magno

  4. Department of Woman and Child Health, University of Padua, Padua, Italy

    Marco Noventa & Salvatore Gizzo

  5. Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy

    Gaetano Valenti & Agnese Maria Chiara Rapisarda

  6. Unit of Psychodiagnostics and Clinical Psychology, University of Catania, Catania, Italy

    Valentina Lucia La Rosa

  7. Department of Obstetrics and Gynecology, University of Nevada Medical School, Reno, NV, USA

    Vani Dandolu

Authors
  1. Sourav Sanchit Patnaik
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  2. Antonio Simone Laganà
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  3. Salvatore Giovanni Vitale
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  4. Salvatore Butticè
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  5. Marco Noventa
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  7. Gaetano Valenti
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  8. Agnese Maria Chiara Rapisarda
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  9. Valentina Lucia La Rosa
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  10. Carlo Magno
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  11. Onofrio Triolo
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  12. Vani Dandolu
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Corresponding author

Correspondence to Antonio Simone Laganà.

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Patnaik, S.S., Laganà, A.S., Vitale, S.G. et al. Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Arch Gynecol Obstet 295, 1341–1359 (2017). https://doi.org/10.1007/s00404-017-4364-2

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  • DOI: https://doi.org/10.1007/s00404-017-4364-2

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