Bladder Pain Syndrome/Interstitial Cystitis

  • Rui Almeida Pinto


Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition characterized by chronic pelvic pain, pressure, or discomfort perceived to be related to the bladder. It is a chronic visceral painful condition of unknown etiology that affects millions of people worldwide. Symptoms can be so severe that patients with BPS/IC may have quality of life with lower scores than those treated for end-stage renal disease. There is no cure for BPS/IC. Thus, the main goal of available treatments is to decrease the intensity of lower urinary tract symptoms, in particular pain. Thus, a tailor-made treatment plan directed toward the patient’s unique clinical phenotype or main complaint should be the gold standard.


Postmenopausal diseases Bladder pain syndrome Pain Interstitial cystitis Diagnosis Treatment 


  1. 1.
    Clemens JQ, Calhoun EA, Litwin MS, et al. A survey of primary care physician practices in the diagnosis and management of women with interstitial cystitis/painful bladder syndrome. Urology. 2010;76(2):323–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Van de Merwe JP, Nordling J, Bouchelouche P, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53(1):60–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Hanno P, Lin A, Nordling J, et al. Bladder pain syndrome committee of the international consultation on incontinence. Neurourol Urodyn. 2010;29(1):191–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Peeker R, Fall M. Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol. 2002;167(6):2470–2.PubMedCrossRefGoogle Scholar
  5. 5.
    Peters KM, Killinger KA, Mounayer MH, et al. Are ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome 2 distinct diseases? A study of coexisting conditions. Urology. 2011;78(2):301–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Killinger KA, Boura JA, Peters KM. Pain in interstitial cystitis/bladder pain syndrome: do characteristics differ in ulcerative and non-ulcerative subtypes? Int Urogynecol J. 2013;24(8):1295–301.PubMedCrossRefGoogle Scholar
  7. 7.
    Rosenberg MT, Hazzard M. Prevalence of interstitial cystitis symptoms in women: a population-based study in the primary care office. J Urol. 2005;174:2231–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Clemens JQ, Meenan RT, O’Keeffe Rosetti MC, et al. Prevalence of interstitial cystitis symptoms in a managed care population. J Urol. 2005;174:576–80.PubMedCrossRefGoogle Scholar
  9. 9.
    Rourke W, Khan SAA, Ahmed K, et al. Painful bladder syndrome/interstitial cystitis: aetiology, evaluation and management. Arch Ital Urol Androl. 2014;86(2):126–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Leppilahti M, Sairanen J, Tammela TL, et al. Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland. J Urol. 2005;174:581–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Warren JW, Jackson TL, Langenberg P, et al. Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis. Urology. 2004;63:17–21.PubMedCrossRefGoogle Scholar
  12. 12.
    Hanno P, Nordling J, Fall M, et al. Bladder pain syndrome. Med Clin N Am. 2011;95:55–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Nickel JC, Shoskes DA, Irvine-Bird K. Prevalence and impact of bacteriuria and/or urinary tract infection in interstitial cystitis/painful bladder syndrome. Urology. 2010;76(4):799–803.PubMedCrossRefGoogle Scholar
  14. 14.
    Dasgupta J, Tincello DG. Interstitial cystitis/bladder pain syndrome: an update. Maturitas. 2009;64(4):212–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Ratliff TL, Klutke CG, Hofmeister M, et al. Role of the immune response in interstitial cystitis. Clin Immunol Immunopathol. 1995;74:209–16.PubMedCrossRefGoogle Scholar
  16. 16.
    Lutgendorf SK, Latini JM, Rothrock N, et al. Autonomic response to stress in interstitial cystitis. J Urol. 2004;172:227–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Ness TJ, Powell-Boone T, Cannon R, et al. Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis. J Urol. 2005;173:1983–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Chelimsky G, McCabe NP, Janata J, et al. Autonomic testing of women with interstitial cystitis/bladder pain syndrome. Clin Auton Res. 2014;24(4):161–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Stein PC, Torri A, Parsons CL. Elevated urinary norepinephrine in interstitial cystitis. Urology. 1999;53(6):1140–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Buffington CA. Norepinephrine content and adrenoceptor function in the bladder of cats with feline interstitial cystitis. J Urol. 2002;167(4):1876–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Buffington CA. Comorbidity of interstitial cystitis with other unexplained clinical conditions. J Urol. 2004;172:1242–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Offiah I, McMahon SB, O’Reilly BA. Interstitial cystitis/bladder pain syndrome: diagnosis and management. Int Urogynecol J. 2013;24(8):1243–56.PubMedCrossRefGoogle Scholar
  23. 23.
    Bullones Rodriguez MA, Afari N, Buchwald DS, et al. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2013;189(1 Suppl):S66.PubMedGoogle Scholar
  24. 24.
    Warren JW, Howard FM, Morozov VV. Is there a high incidence of hysterectomy and other nonbladder surgeries before and after onset of interstitial cystitis/bladder pain syndrome? Am J Obstet Gynecol. 2013;208(1):77e1–6.CrossRefGoogle Scholar
  25. 25.
    Madersbacher H, van Ophoven A, van Kerrebroeck PE. GAG layer replenishment therapy for chronic forms of cystitis with intravesical glycosaminoglycans—a review. Neurourol Urodyn. 2013;32(1):9–18.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang CO, Wang JY, Koch KR, et al. Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis. J Urol. 2005;174:2382–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Shie JH, Liu HT, Kuo HC. Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. Urology. 2012;79(2):484e7–484e13.CrossRefGoogle Scholar
  28. 28.
    Hohenfellner M, Nunes L, Schmidt RA, et al. Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis. J Urol. 1992;147(3):587–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Dickson A, Avelino A, Cruz F, Ribeiro-da-Silva A. Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat urinary bladder in a chronic model of cyclophosphamide-induced cystitis. Neuroscience. 2006;141(3):1633–47.PubMedCrossRefGoogle Scholar
  30. 30.
    Ochodnicky P, Cruz CD, Yoshimura N, et al. Neurotrophins as regulators of urinary bladder function. Nat Rev Urol. 2012;9(11):628–37.PubMedCrossRefGoogle Scholar
  31. 31.
    Kiuchi H, Tsujimura A, Takao T, et al. Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations. BJU Int. 2009;104(6):826–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Tripp DA, Nickel JC, Wong J, et al. Mapping of pain phenotypes in female patients with bladder pain syndrome/interstitial cystitis and controls. Eur Urol. 2012;62(6):1188–94.PubMedCrossRefGoogle Scholar
  33. 33.
    O’Leary MP, Sant G. The interstitial cystitis symptom and problem indices: rationale, development, and application. In: Sant G, editor. Interstitial cystitis. Philadelphia: Lippincott-Raven; 1997. p. 271–6.Google Scholar
  34. 34.
    Hanno P, Dmochowski R. Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn. 2009;28(4):274–86.PubMedCrossRefGoogle Scholar
  35. 35.
    Larsen MS, Mortensen S, Nordling J, et al. Quantifying mast cells in bladder pain syndrome by immunohistochemical analysis. BJU Int. 2008;102:204–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Parsons CL, Greenberger M, Gabal L, et al. The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol. 1998;159(6):186206.CrossRefGoogle Scholar
  37. 37.
    Alp BF, Akyol I, Adayener C, et al. The significance of potassium chloride sensitivity test and urinary uronic acid level in the diagnosis of chronic pelvic pain syndrome. Int Urol Nephrol. 2009;41(3):483–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Lee SW, Liong ML, Yuen KH, et al. Acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic pain. Am J Med. 2008;121(1):1–7.CrossRefGoogle Scholar
  39. 39.
    Moutzouris DA, Falagas ME. Interstitial cystitis: an unsolved enigma. Clin J Am Soc Nephrol. 2009;4(11):1844–57.PubMedCrossRefGoogle Scholar
  40. 40.
    Hanno P. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997;49(Suppl 5A):93–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Foster HE Jr, Hanno PM, Nickel JC, et al. Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010;183(5):1853–8.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Fall M, Oberpenning F, Peeker R. Treatment of bladder pain syndrome/interstitial cystitis: can we make evidence-based decisions? Eur Urol. 2008;54(1):65–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Moldwin RM, Evans RJ, Stanford EJ, et al. Rational approaches to the treatment of patients with interstitial cystitis. Urology. 2007;69(4 Suppl):73–81.PubMedCrossRefGoogle Scholar
  44. 44.
    Evans RJ, Moldwin RM, Cossons N, et al. Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J Urol. 2011;185(5):1716–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Keay S, Kaczmarek P, Zhang CO, et al. Normalization of proliferation and tight junction formation in bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome by D-Proline and D-Pipecolic acid derivatives of antiproliferative factor. Chem Biol Drug Des. 2011;77(6):421–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Sanchez Freire V, Burkhard FC, et al. MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome. Am J Pathol. 2010;176(1):288–303.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Tambaro S, Casu MA, Mastinu A, et al. Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis. Eur J Pharmacol. 2014;729:67–74.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen H, Wang F, Chen W, et al. Efficacy of daily low-dose sildenafil for treating interstitial cystitis: results of a randomized, double-blind, placebo-controlled trial—treatment of interstitial cystitis/painful bladder syndrome with low-dose sildenafil. Urology. 2014;84(1):51–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Perez-Marrero R, Emerson LE, Feltis JT. A controlled study of dimethyl sulfoxide in interstitial cystitis. J Urol. 1988;140(1):36–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Stav K, Beberashvili I, Lindner A, et al. Predictors of response to intravesical sulfoxide cocktail in patients with interstitial cystitis. Urology. 2012;80(1):61–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Taneja R. Intravesical lignocaine in the diagnosis of bladder pain syndrome. Int Urogynecol J. 2010;21(3):321–4.PubMedCrossRefGoogle Scholar
  52. 52.
    Nickel JC, Moldwin R, Lee S, Davis EL, et al. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int. 2009;103(7):910–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Davis EL, El Khoudary SR, Talbott EO, Davis J, Regan LJ. Safety and efficacy of the use of intravesical and oral pentosan polysulfate sodium for interstitial cystitis: a randomized double-blind clinical trial. J Urol. 2008;179(1):177–85.PubMedCrossRefGoogle Scholar
  54. 54.
    Engelhardt PF, Morakis N, Daha LK, Esterbauer B, Riedl CR. Long-term results of intravesical hyaluronan therapy in bladder pain syndrome/interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct. 2011;22(4):401–5.CrossRefGoogle Scholar
  55. 55.
    Payne CK, Mosbaugh PG, Forrest JB, et al. Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol. 2005;173:1590–4.PubMedCrossRefGoogle Scholar
  56. 56.
    Propert KJ, Mayer R, Nickel JC, et al. Follow-up of patients with interstitial cystitis responsive to treatment with intravesical bacillus Calmette-Guerin or placebo. J Urol. 2008;179(2):552–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Hsieh CH, Chang ST, Hsieh CJ, et al. Treatment of interstitial cystitis with hydrodistention and bladder training. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(10):1379–84.PubMedCrossRefGoogle Scholar
  58. 58.
    Rofeim O, Hom D, Freid RM, et al. Use of the neodymium: YAG laser for interstitial cystitis: a prospective study. J Urol. 2001;166(1):134–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Gajewski JB, Al-Zahrani AA. The long-term efficacy of sacral neuromodulation in the management of intractable cases of bladder pain syndrome: 14 years of experience in one centre. BJU Int. 2011;107(8):1258–64.PubMedCrossRefGoogle Scholar
  60. 60.
    O’Reilly BA, Dwyer PL, Hawthorne G, et al. Transdermal posterior tibial nerve laser therapy is not effective in women with interstitial cystitis. J Urol. 2004;172:1880–3.PubMedCrossRefGoogle Scholar
  61. 61.
    Tanaka T, Nitta Y, Morimoto K, et al. Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan. BMC Urol. 2011;24:11.CrossRefGoogle Scholar
  62. 62.
    Cruz F. Targets for botulinum toxin in the lower urinary tract. Neurourol Urodyn. 2014;33(1):31–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Kuo HC. Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis. Int J Urol. 2014;21(Suppl 1):34–41.PubMedCrossRefGoogle Scholar
  64. 64.
    Peng CH, Jhang JF, Shie JH, et al. Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical Onabotulinum toxin A injections combined with hydrodistention for patients with interstitial cystitis - clinical results and immunohistochemistry analysis. Urology. 2013;82(6):1452.e1–6.CrossRefGoogle Scholar
  65. 65.
    Giannantoni A, Porena M, Costantini E, et al. Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup. J Urol. 2008;179(3):1031–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Kuo HC, Chancellor MB. Comparison of intravesical botulinum toxin type A injections plus hydrodistension with hydrodistension alone for the treatment of refractory interstitial cystitis/painful bladder syndrome. BJU Int. 2009;1:1–5.Google Scholar
  67. 67.
    Pinto R, Lopes T, Frias B, Silva A, Silva JA, Silva CM, Cruz C, Cruz F, Dinis P. Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis. Eur Urol. 2010;58(3):360–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Pinto R, Lopes T, Silva J, Silva C, Dinis P, Cruz F. Persistent therapeutic effect of repeated injections of onabotulinum toxin a in refractory bladder pain syndrome/interstitial cystitis. J Urol. 2013;189(2):548–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Pinto R, Costa D, Morgado A, Pereira P, Charrua A, Silva J, Cruz F. Intra- Trigonal Onabotulinum Toxin A improves bladder symptoms and quality of life in bladder pain syndrome/interstitial cystitis patients—a pilot, single centre, randomized, double-blind, placebo-controlled trial. J Urol. 2018;199(4):998–1003.PubMedCrossRefGoogle Scholar
  70. 70.
    Rossberger J, Fall M, Jonsson O, et al. Long-term results of reconstructive surgery in patients with bladder pain syndrome/interstitial cystitis: sub-typing is imperative. Urology. 2007;70(4):638–42.PubMedCrossRefGoogle Scholar
  71. 71.
    Kochakarn W, Lertsithichai P, Pummangura W. Bladder substitution by ileal neobladder for women with interstitial cystitis. Int Braz J Urol. 2007;33(4):486–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Rui Almeida Pinto
    • 1
    • 2
    • 3
  1. 1.Department of UrologyHospital de S. JoãoPortoPortugal
  2. 2.Faculty of Medicine of PortoPortoPortugal
  3. 3.i3S (Institute of Innovation and Investigation in Health)PortoPortugal

Personalised recommendations