Skip to main content
SpringerLink
Log in

Pharmacologic Goals in Interstitial Cystitis/Bladder Pain Syndrome

  • Chapter
  • First Online:
Bladder Pain Syndrome – An Evolution

  • 628 Accesses

Abstract

During the last 30 years, a number of treatments and management algorithms have been developed and applied in the treatment of patients with Interstitial Cystitis/Bladder Painful Syndrome (IC/BPS), and many behavioral, dietary, interventional, pharmacologic and surgical therapies have been developed in the attempt to control the disease and to offer substantial benefits to the affected patients. Nevertheless, the complexity of the disease in terms of aetiology and pathogenesis still has made it difficult to induce significant and long-lasting benefits for any kind of these treatments. In addition, few well designed, randomised controlled trials have been conducted until now on different treatment modalities, and this still precludes the development of evidence-based management strategies. Indeed, the majority of pharmacological agents used to treat patients with IC/BPS are still off label. In this respect, the Interstitial Cystitis Data Base study noted >180 treatment modalities for IC/BPS, with poor results in the majority of cases [1]. To date, there is general agreement on the use of some agents, orally or intravesically administered, as indicated by the EAU guidelines on chronic pelvic pain [2] and the AUA Guidelines for the Diagnosis and Treatment of Interstitial Cystitis/ Bladder Pain Syndrome [3].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rovner E, Propert KJ, Brensinger C, Wein AJ, Foy M, Kirkemo A, Landis JR, Kusek JW, Nyberg LM. Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group. Urology. 2000;56(6):940–5.

    Article  CAS  PubMed  Google Scholar 

  2. Engeler DS, Baranowski AP, Dinis-Oliveira P, Elneil S, Hughes J, Messelink EJ, van Ophoven A, Williams AC, European Association of Urology. The 2013 EAU guidelines on chronic pelvic pain: is management of chronic pelvic pain a habit, a philosophy, or a science? 10 years of development. Eur Urol. 2013;64:431–9.

    Article  PubMed  Google Scholar 

  3. Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM, Interstitial Cystitis Guidelines Panel of the American Urological Association Education and Research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185:2162–70.

    Article  PubMed  Google Scholar 

  4. Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ. Contemporary management of the painful bladder: a systematic review. Eur Urol. 2012;61:29–53.

    Article  PubMed  Google Scholar 

  5. Davis NF, Brady CM, Creagh T. Interstitial cystitis/painful bladder syndrome: epidemiology, pathophysiology and evidence-based treatment options. Eur J Obstet Gynecol Reprod Biol. 2014;175:30–7.

    Article  CAS  PubMed  Google Scholar 

  6. Pazin C, Moreira de Souza Mitidieri A, Moreira Silva AP, Ferreira Gurian MB, Poli-Neto OB, Rosa-e-Silva JC. Treatment of bladder pain syndrome and interstitial cystitis: a systematic review. Int Urogynecol J. 2016;27:697–708.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. Ogawa T, Ishizuka O, Ueda T, Tyagi P, Chancellor MB, Yoshimura N. Current and emerging drugs for interstitial cystitis/bladder pain syndrome (IC/BPS). Expert Opin Emerg Drugs. 2015;20(4):555–70.

    Article  CAS  PubMed  Google Scholar 

  9. Fall M, Logadottir Y, Peeker R. Interstitial cystitis is bladder pain syndrome with Hunner’s lesion. Int J Urol. 2014;21(Suppl 1):79–82.

    Article  PubMed  Google Scholar 

  10. Nickel JC, Irvine-Bird K, Jianbo L, et al. Phenotype-directed management of interstitial cystitis/bladder pain syndrome. Urology. 2014 Jul;84(1):175–9.

    Article  PubMed  Google Scholar 

  11. Hurst RE. Structure, function and pathology of proteoglycans and glycosaminoglycans in the urinary tract. World J Urol. 1994;12:3–10.

    Article  CAS  PubMed  Google Scholar 

  12. Emtage J, Morales A, Heaton JPW, Perez-Marrero R. Heparin in the treatment of interstitial cystitis. J Urol. 1985;133:168.

    Google Scholar 

  13. Morales A, Emerson L, Nickel JC, Lundie M. Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. J Urol. 1996;156:45–9.

    Article  CAS  PubMed  Google Scholar 

  14. Bade JJ, Laseur M, Nieuwenburg LT, van der Weele LT, Mensink HJ. A placebo-controlled study of intravesical Pentosanpolysulfate for the treatment of interstitial cystitis. Br J Urol. 1997;79:168–71.

    Article  CAS  PubMed  Google Scholar 

  15. Parsons CL, Schmidt JD, Pollen JJ. Successful treatment of interstitial cystitis with sodium pentosan polysulfate. J Urol. 1983;130:51–3.

    Article  CAS  PubMed  Google Scholar 

  16. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997;49(5A Suppl):93–9.

    Article  CAS  PubMed  Google Scholar 

  17. Jepsen JV, Sall M, Rhodes PR, Schmidt D, Messing E, Bruskewitz RC. Long term experience with pentosanpolysulfate in interstitial cystitis. Urology. 1998;51:381–7.

    Article  CAS  PubMed  Google Scholar 

  18. Nickel JC, Kaufman DM, Zhang HF, Wan GJ, Sand PK. Time to initiation of pentosan polysulfate sodium treatment after interstitial cystitis diagnosis: effect on symptom improvement. Urology. 2008;71:57–61.

    Article  PubMed  Google Scholar 

  19. Sand PK, Kaufman DM, Evans RJ, Zhang HF, Alan Fisher DL, Nickel JC. Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction. Curr Med Res Opin. 2008;24:2259–64.

    Article  CAS  PubMed  Google Scholar 

  20. Chuang YC, Lee WC, Lee WC, Chiang PH. Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol. 2009;182:1393–400.

    Article  CAS  PubMed  Google Scholar 

  21. Parsons CL, Benson G, Childs SJ, Hanno P, Sant GR, Webster G. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J Urol. 1993;150:845–8.

    Article  CAS  PubMed  Google Scholar 

  22. Sant GR, Propert KJ, Hanno PM, et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003;170:810–5.

    Article  CAS  PubMed  Google Scholar 

  23. Nickel JC, Barkin J, Forrest J, et al. Randomized, double-blind, dose ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology. 2005;65:654–8.

    Article  PubMed  Google Scholar 

  24. Sairanen J, Tammela TLJ, Leppilahti M, et al. Cyclosporine A and pentosanpolysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study. J Urol. 2005;174:2235–8.

    Article  CAS  PubMed  Google Scholar 

  25. 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;179:177–85.

    Article  CAS  PubMed  Google Scholar 

  26. Sorensen RB. Chondroitin sulphate in the treatment of interstitial cystitis and chronic inflammatory disease of the urinary bladder. Eur Urol Suppl. 2003;2(4):16–8.

    Article  CAS  Google Scholar 

  27. Steinhoff G. The efficacy of chondroitin sulphate in treating interstitial cystitis. Eur Urol Suppl. 2003;14-16(10):2.

    Google Scholar 

  28. Nickel JC, Egerdie B, Downey J, Singh R, Skehan A, Carr L, Irvine-Bird K. A real-life multi-centre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulfate for the treatment of interstitial cystitis. BJU Int 2008;103:56–6.

    Google Scholar 

  29. Nordling J, van Ophoven A. Intravesical Glysosaminoglycan replenishment with chondroitin sulfate in chronic forms of cystitis. Arzneimittelforschung. 2008;58:328–35.

    CAS  PubMed  Google Scholar 

  30. Nickel JC, Egerdie RB, Steinhoff G, Palmer B, Hanno P. A multicenter, randomized, double-blind, parallel group pilot evaluation of the efficacy and safety of intravesical sodium chondroitin sulfate versus vehicle control in patients with interstitial cystitis/painful bladder syndrome. Urology. 2010;76:804–9.

    Article  PubMed  Google Scholar 

  31. Riedl CR, Engelhardt PF, Daha KL, Morakis N, Pflüger H. Hyaluronan treatment of interstitial cystitis/painful bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19:717–21.

    Article  PubMed  Google Scholar 

  32. Daha LK, Riedl CR, Lazar D, Hohlbrugger G, Pflüger H. Do cystometric findings predict the results of intravesical hyaluronic acid in women with interstitial cystitis? Eur Urol. 2005;47:393–7.

    Article  PubMed  Google Scholar 

  33. Shao Y, Shen ZJ, RuiWB ZWL. Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis. J Urol. 2010;75:547–50.

    Article  Google Scholar 

  34. Thilagarajah R, Witherow RO, Walker MM. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double-blind placebo-controlled trial. BJU Int. 2001;87:207–12.

    Article  CAS  PubMed  Google Scholar 

  35. van Ophoven A, Pokupic S, Heinecke A, Hertle L. A prospective, randomized, placebo controlled, double-blind study ofamitriptyline for the treatment of interstitial cystitis. J Urol. 2004;172:533–6.

    Article  PubMed  Google Scholar 

  36. Foster HE, Hanno PM, Nickel JC, et al. Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/ painful bladder syndrome. J Urol. 2010;183:1853–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. van Ophoven A, Hertle L. The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study. J Urol. 2007;177:552–5.

    Article  PubMed  Google Scholar 

  38. Kapturczak MH, Meier-Kriesche HU, Kaplan B. Pharmacology of calcineurin antagonists. Transplant Proc. 2004;36(2 Suppl):25S–32S.

    Article  CAS  PubMed  Google Scholar 

  39. Moran PA, Dwyer PL, Carey MP, Maher CF, Radford NJ. Oral methotrexate in the management of refractory interstitial cystitis. Aust N Z J Obstet Gynaecol. 1999;39(4):468–71.

    Article  CAS  PubMed  Google Scholar 

  40. Ueda T, Tamaki M, Ogawa O, Yamauchi T, Yoshimura N. Improvement of interstitial cystitis symptoms and problems that developed during treatment with oral IPD-1151T. J Urol. 2000;164:1917–20.

    Article  CAS  PubMed  Google Scholar 

  41. Ochodnicky P, Cruz CD, Yoshimura N, Cruz F. Neurotrophins as regulators of urinary bladder function. Nat Rev Urol. 2012;9(11):628–37.

    CAS  PubMed  Google Scholar 

  42. Lowe EM, Anand P, Terenghi G, et al. Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 1997;79(4):572–7.

    Article  CAS  PubMed  Google Scholar 

  43. Okragly AJ, Niles AL, Saban R, et al. Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol. 1999;161(2):438–41. discussion 41-2

    Article  CAS  PubMed  Google Scholar 

  44. HC Q, Zhang W, Yan S, et al. Urinary nerve growth factor could be a biomarker for interstitial cystitis/painful bladder syndrome: a meta-analysis. PLoS One. 2014;9(9):e106321.

    Article  Google Scholar 

  45. 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.

    Article  CAS  PubMed  Google Scholar 

  46. Wang H, Russell LJ, Kelly KM, Wang S, Thipphawong J. Fulranumab in patients with interstitial cystitis/bladder pain syndrome: observations from a randomized, double-blind, placebo-controlled study. BMC Urol. 2017;17(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Tyagi P, Kashyap M, Majima T, Kawamorita N, Yoshizawa T, Yoshimura N. Intravesical liposome therapy for interstitial cystitis. Int J Urol. 2017;24(4):267–71.

    Article  Google Scholar 

  48. Henry RA, Morales A, Cahill CM. Beyond a simple anesthetic effect: lidocaine in the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Urology. 2015;85(5):1025–33.

    Article  PubMed  Google Scholar 

  49. Nickel JC, Moldwin R, Lee S, 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.

    Article  CAS  PubMed  Google Scholar 

  50. Nickel JC, Jain P, Shore N, et al. Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: safety and efficacy of a new drug delivery device. Sci Transl Med. 2012;4(143):143ra00.

    Article  Google Scholar 

  51. Cockayne DA, Hamilton SG, Zhu QM, et al. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature. 2000;407(6807):1011–5.

    Article  CAS  PubMed  Google Scholar 

  52. Sun Y, Chai TC. Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis. BJU Int. 2002;90(4):381–5.

    Article  CAS  PubMed  Google Scholar 

  53. Sun Y, Keay S, De Deyne PG, et al. Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. J Urol. 2001;166(5):1951–6.

    Article  CAS  PubMed  Google Scholar 

  54. Sun Y, Chai TC. Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol. 2004;171(1):448–52.

    Article  CAS  PubMed  Google Scholar 

  55. Sun Y, Chai TC. Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis. Am J Physiol Cell Physiol. 2006;290(1):C27–34.

    Article  CAS  PubMed  Google Scholar 

  56. Moldwin R, Kitt M, Mangel J, Beyer R, Hanno P, Butera P, Ford A. A phase 2 study in women with interstitial cystitis/bladder pain syndrome (IC/BPS) of the novel P2X3 antagonist AF-219 (Abstract #23), 45th International Continence Society (ICS) Annual Meeting, Montreal, Canada, 2015.

    Google Scholar 

  57. Stenton GR, Mackenzie LF, Tam P, et al. Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 1. Effects on inflammatory cell activation and chemotaxis in vitro and pharmacokinetic characterization in vivo. Br J Pharmacol. 2013;168(6):1506–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Nickel JC, Egerdie B, Davis E, Evans R, Mackenzie L, Shrewsbury SB. A phase II study of the efficacy and safety of the novel oral SHIP1 activator AQX-1125 in subjects with moderate to severe interstitial cystitis/bladder pain syndrome. J Urol. 2016;196(3):747–54.

    Article  CAS  PubMed  Google Scholar 

  59. Ogawa T, Homma T, Igawa Y, et al. CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. J Urol. 2010;183(3):1206–12.

    Article  CAS  PubMed  Google Scholar 

  60. Fall M, Johansson SL, Aldenborg F. Chronic interstitial cystitis: a heterogeneous syndrome. J Urol. 1987;137(1):35–8.

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  PubMed  Google Scholar 

  62. Fall M, Baranowski AP, Elneil S, et al. EAU guidelines on chronic pelvic pain. Eur Urol. 2010;57(1):35–48.

    Article  PubMed  Google Scholar 

  63. Logadottir Y, Fall M, Kabjorn-Gustafsson C, et al. Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis. Scand J Urol Nephrol. 2012;46(5):365–70.

    Article  PubMed  Google Scholar 

  64. Wennevik GE, Meijlink JM, Hanno P, Nordling J. The role of glomerulations in bladder pain syndrome: a review. J Urol. 2016;195(1):19–25.

    Article  PubMed  Google Scholar 

  65. Ueda T, Nakagawa M, Okamura M, et al. New cystoscopic diagnosis for interstitial cystitis/painful bladder syndrome using narrow-band imaging system. Int J Urol. 2008;15(12):1039–43.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Urology Section, Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy

    Antonella Giannantoni M.D., Ph.D. & Marilena Gubbiotti M.D.

  2. Department of Urology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Naoki Yoshimura M.D., Ph.D.

  3. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA

    Karl-Erik Andersson M.D., Ph.D.

Authors
  1. Antonella Giannantoni M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marilena Gubbiotti M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoki Yoshimura M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karl-Erik Andersson M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonella Giannantoni M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Stanford University School of Medicine, Stanford, California, USA

    Philip M. Hanno

  2. Department of Urology, Herlev Hospital, Herlev, Denmark

    Jørgen Nordling

  3. St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA

    David R. Staskin

  4. Penn Medicine, Perelman School of Medicine, Perelman Center for Advanced Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA

    Alan J. Wein

  5. Urology, Antwerp University, GGW, Wilrijk, Antwerp, Belgium

    Jean Jacques Wyndaele

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Giannantoni, A., Gubbiotti, M., Yoshimura, N., Andersson, KE. (2018). Pharmacologic Goals in Interstitial Cystitis/Bladder Pain Syndrome. In: Hanno, P., Nordling, J., Staskin, D., Wein, A., Wyndaele, J. (eds) Bladder Pain Syndrome – An Evolution. Springer, Cham. https://doi.org/10.1007/978-3-319-61449-6_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-61449-6_19

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-61448-9

  • Online ISBN: 978-3-319-61449-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation