Etiology of Interstitial Cystitis and the Role of Pentosanpolysulfate in IC Therapy

  • C. Lowell ParsonsEmail author


For over 40 years I have studied the bladder epithelium and interstitial cystitis (IC). I have seen over 9000 patients and conducted extensive basic laboratory and clinical research on IC that has substantially changed my concepts of the disease. My understanding now is that there is one primary disease process that generates bladder symptoms of urgency, frequency, pain and incontinence (in any combination) in women of all ages and men less than 55 (before the age of bladder outlet obstruction). This pathologic process is a dysfunctional, “leaky” bladder epithelium that allows urinary potassium to diffuse into the bladder interstitium and directly depolarize, nerves, muscles, cause bladder symptoms and injure tissue. The rare but not separate severe form of this process is the patient historically diagnosed with IC [1].


  1. 1.
    Parsons CL. The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain. BJU Int. 2011;107:370–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Parsons CL, Stauffer C, Schmidt JD. Bladder-surface glycosaminoglycans: an efficient mechanism of environmental adaptation. Science. 1980;208(4444):605–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Parsons CL, Greenspan C, Mulholland SG. The primary antibacterial defense mechanism of the bladder. Investig Urol. 1975;13(1):72–8.Google Scholar
  4. 4.
    Parsons CL, et al. Bladder surface glycosaminoglycans: an epithelial permeability barrier. J Urol. 1990;143(1):139–42.CrossRefPubMedGoogle Scholar
  5. 5.
    Lilly JD, Parsons CL. Bladder surface glycosaminoglycans is a human epithelial permeability barrier. Surg Gynecol Obstet. 1990;171(6):493–6.PubMedGoogle Scholar
  6. 6.
    Parsons CL, Lilly JD, Stein P. Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J Urol. 1991;145(4):732–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Parsons CL, et al. The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol. 1998;159(6):1862–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Parsons CL, Stauffer CW, Schmidt JD. Reversible inactivation of bladder surface glycosaminoglycan antibacterial activity by protamine sulfate. Infect Immun. 1988;56(5):1341–3.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Parsons CL, Mulholland SG, Anwar H. Antibacterial activity of bladder surface mucin duplicated by exogenous glycosaminoglycan (heparin). Infect Immun. 1979;24(2):552–7.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Parsons CL, Pollen JJ, Anwar H, Stauffer C, Schmidt JD. Antibacterial activity of bladder surface mucin duplicated in the rabbit bladder by exogenous glycosaminoglycan (sodium pentosanpolysulfate). Infect Immun. 1980;27(3):876–81.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Mulholland SG, Hanno P, Parsons CL, Sant GR, Staskin DR. Pentosanpolysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study. Urology. 1990;35(6):552–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Parsons CL, Benson G, Childs SJ, Hanno P, Sant GR, Webster GJ. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. Urology. 1993;150(3):845–8.CrossRefGoogle Scholar
  13. 13.
    Parsons CL, Mulholland SG. Successful therapy of interstitial cystitis with pentosanpolysulfate. J Urol. 1987;138:513–16.Google Scholar
  14. 14.
    Parsons CL, et al. Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis. Neurourol Urodyn. 1994;13(5):515–20.Google Scholar
  15. 15.
    Parsons CL, Zupkas P, Parsons JK. Intravesical potassium sensitivity in patients with interstitial cystitis and urethral syndrome. Urology. 2001;57(3):428–32. discussion 432-3.CrossRefPubMedGoogle Scholar
  16. 16.
    Parsons CL, et al. The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity. Am J Obstet Gynecol. 2002;187(5):1395–400.CrossRefPubMedGoogle Scholar
  17. 17.
    Parsons CL, et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology. 2002;60(4):573–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Parsons CL, Albo M. Intravesical potassium sensitivity in patients with prostatitis. J Urol. 2002;168(3):1054–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kahn BS, Tatro C, Parsons CL, Willems JJ. Prevalence of interstitial cystitis in vulvodynia patients detected by bladder potassium sensitivity. J Sex Med. 2010;7(2 Pt 2):996–1002.CrossRefPubMedGoogle Scholar
  20. 20.
    Parsons CL, et al. Quantifying symptoms in men with interstitial cystitis/prostatitis, and its correlation with potassium-sensitivity testing. BJU Int. 2005;95(1):86–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Parsons CL, Shaw T, Berecz Z, Su Y, Zupkas P, Argade S. Role of urinary cations in the aetiology of bladder symptoms and interstitial cystitis. BJU Int. 2014;114(2):286–93.CrossRefPubMedGoogle Scholar
  22. 22.
    Hassan AA, Elgamal SA, Sabaa MA, Salem K. Evaluation of intravesical potassium sensitivity test and bladder biopsy in patients with chronicprostatitis/chronic pelvic pain syndrome. Int J Urol. 2007;14(8):738–42.Google Scholar
  23. 23.
    Argade S, Berecz Z, Su Y, Parsons CL. Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms. World J Urol. 2016;34(12):1685–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Jiang YH, Jhang JF, Kuo HC. Revisiting the role of potassium sensitivity testing and cystoscopic hydrodistention for the diagnosis of interstitial cystitis. PLoS One. 2016;11(3):e0151692. doi: 10.1371/journal.pone.0151692.
  25. 25.
    Minaglia S, Ozel B, Bizhang R, Mishell DR Jr. Increased prevalence of interstitial cystitis in women with detrusor overactivity refractory to anticholinergic therapy. Urology. 2005;66(4):702–6.Google Scholar
  26. 26.
    Hanno PM, Parsons CL, Shrom SH, Fritz R, Mulholland SG. The protective effect of heparin in experimental bladder infection. J Surg Res. 1978;25(4):324–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Parsons CL, Schmidt JD, Pollen JJ. Successful treatment of interstitial cystitis with sodium pentosanpolysulfate. J Urol. 1983;130(1):51–3.CrossRefPubMedGoogle Scholar
  28. 28.
    Holm-Bentzen M, Jacobsen F, Nerstrøm B, Lose G, Kristensen JK, Pedersen RH, Krarup T, Feggetter J, Bates P, Barnard R, et al. A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease. J Urol. 1987;138(3):503–7.Google Scholar
  29. 29.
    Parsons CL. How does interstitial cystitis begin? Transl Androl Urol. 2015;4(6):605–10. doi: 10.3978/j.issn.2223-4683.2015.11.02.PMID:26816860.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Parsons CL, Forrest J, Nickel JC, Evans R, Lloyd LK, Barkin J, Mosbaugh PG, Kaufman DM, Hernandez-Graulau JM, Atkinson L, Albrecht D, Elmiron Study Group. Effect of pentosan polysulfate therapy on intravesical potassium sensitivity. Urology. 2002;59(3):329–33.CrossRefPubMedGoogle Scholar
  31. 31.
    Nickel JC, Barkin J, Forrest J, Mosbaugh PG, Hernandez-Graulau J, Kaufman D, Lloyd K, Evans RJ, Parsons CL, Atkinson LE, Elmiron Study Group. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology. 2005;65(4):654–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Parsons CL. Diagnosing the bladder as the source of pelvic pain: successful treatment for adults and children. Pain Manage. 2014;4(4):293–301.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.School of MedicineUniversity of California San DiegoLa JollaUSA

Personalised recommendations