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Bladder Pain Syndrome Associated with Interstitial Cystitis: Recent Research and Treatment Options

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Abstract

Purpose of Review

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain syndrome of unknown etiology, the pathophysiology of which has not been fully explored. This article reports recently published research in diagnosis and treatment of IC/BPS.

Recent Findings

Current research shows that the syndrome is likely heterogeneous, with different pathogeneses, clinical characteristics, cystoscopic findings, and characteristics of urine biomarkers. Chronic bladder inflammation results in deficits in the bladder urothelial barrier in addition to increased apoptosis and impaired regeneration of urothelial cells, causing bladder pain symptoms and urinary frequency and urgency. The initial therapeutic approach is conservative treatment with lifestyle modification, anti-inflammatory drugs, and intravesical glycosaminoglycan replenishment and dimethyl sulfoxide instillation. In patients with non-Hunner’s lesion IC/BPS refractory to conventional therapy, intravesical botulinum toxin A injection and sacral neuromodulation may be tried. Experimental therapies are intravesical platelet-rich plasma, low-energy shock wave bladder treatment and bladder instillation of liposomes with or without mixed botulinum toxin A. For IC/BPS patients with Hunner’s lesion, electrocauterization or laser ablation is the first-line treatment. Patients with Epstein-Barr virus infection may also benefit from antiviral therapy. For patients with Hunner’s IC/BPS and a contracted bladder, partial cystectomy with augmentation enterocystoplasty or total cystectomy with urinary diversion should be the last resort for treatment to address early elimination and bladder pain and to resume normal lower urinary tract function.

Summary

IC/BPS remains a mysterious bladder disease with chronic inflammation and urothelial dysfunction and involves functional somatic disorders. Treatment should be multidisciplinary and target at potential pathogenesis of the disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gohritz A, Dellon AL. Bladder pain syndome/interstitial cystitis due to pudendal nerve compression: described in 1915-A reminder for treating pelvic pain a century later. J Brachial Plex Peripher Nerve Inj. 2020;15:e5–8.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Messing EM, Stamey TA. Interstitial cystitis: early diagnosis, pathology, and treatment. Urology. 1978;12:381–92.

    Article  CAS  PubMed  Google Scholar 

  3. • Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208:34–42. A guideline directing the accurate diagnosis and principle of treatment in patients with IC/BPS.

    Article  PubMed  Google Scholar 

  4. • Akiyama Y, Luo Y, Hanno PM, Maeda D, Homma Y. Interstitial cystitis/bladder pain syndrome: the evolving landscape, animal models and future perspectives. Int J Urol. 2020;27:491–503. A comprehensive review of pathophysiology of patients with HIC and NHIC.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Homma Y, Akiyama Y, Tomoe H, Furuta A, Ueda T, Maeda D, Lin AT, Kuo HC, Lee MH, Oh SJ, Kim JC, Lee KS. Clinical guidelines for interstitial cystitis/bladder pain syndrome. Int J Urol. 2020;27:578–89.

    Article  PubMed  Google Scholar 

  6. van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, Elneil S, Fall M, Hohlbrugger G, Irwin P, Mortensen S, van Ophoven A, Osborne JL, Peeker R, Richter B, Riedl C, Sairanen J, Tinzl M, Wyndaele JJ. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53:60–7.

    Article  PubMed  Google Scholar 

  7. Homma Y, Ueda T, Tomoe H, Lin AT, Kuo HC, Lee MH, Lee JG, Kim DY, Lee KS. Interstitial cystitis guideline committee. Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome. Int J Urol. 2009;16:597–615.

    Article  PubMed  Google Scholar 

  8. 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  PubMed Central  Google Scholar 

  9. Lee MH, Lin AT, Kuo HC, Chen YF. Clinical characteristic picture and impact of symptoms on quality of life of interstitial cystitis patients in Taiwan. Low Urin Tract Symptoms. 2014;6:20–5.

    Article  PubMed  Google Scholar 

  10. Nickel JC. Interstitial cystitis: a chronic pelvic pain syndrome. Med Clin North Am. 2004;88:467–81.

    Article  PubMed  Google Scholar 

  11. • Jhang JF, Jiang YH, Kuo HC. Current understanding of the pathophysiology and novel treatments of interstitial cystitis/bladder pain syndrome. Biomedicines. 2022;10:2380. A comprehensive review of the histopathology of IC/BPS and treatment guidance based on the underlying pathophysiology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. •• Jiang YH, Jhang JF, Hsu YH, Kuo HC. Usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome. Int J Mol Sci. 2022;23:12044. This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with IC/BPS. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jiang YH, Peng CH, Liu HT, Kuo HC. Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis/bladder pain syndrome. PLoS One. 2013;8:e76779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lin HY, Lu JH, Chuang SM, Chueh KS, Juan TJ, Liu YC, Juan YS. Urinary biomarkers in interstitial cystitis/bladder pain syndrome and its impact on therapeutic outcome. Diagnostics (Basel). 2021;12:75.

    Article  PubMed  PubMed Central  Google Scholar 

  15. • Jiang YH, Jhang JF, Hsu YH, Ho HC, Wu YH, Kuo HC. Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics. Am J Physiol Renal Physiol. 2020;318:F1391–9. Patients with IC/BPS have distinct higher urinary cytokines level, which can be useful in identifying IC from the other sensory bladder diseases.

    Article  CAS  PubMed  Google Scholar 

  16. Liu HT, Tyagi P, Chancellor MB, Kuo HC. Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity. BJU Int. 2010;106:1681–5.

    Article  PubMed  Google Scholar 

  17. • Jhang JF, Jiang YH, Hsu YH, Ho HC, Kuo HC. Decreased urothelial cytoskeleton and cell proliferation protein expression suggest interstitial cystitis/bladder pain syndrome patients with Hunner's lesion and grade 3 glomerulation might be different from other types of patients. Int J Urol. 2021;28:823–30. Patients with HIC and NHIC with high-grade glomerulations had impaired urothelial cytoskeletal protein expressions.

    Article  CAS  PubMed  Google Scholar 

  18. Lee YK, Jhang JF, Jiang YH, Hsu YH, Ho HC, Kuo HC. Difference in electron microscopic findings among interstitial cystitis/bladder pain syndrome with distinct clinical and cystoscopic characteristics. Sci Rep. 2021;11:17258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hauser PJ, VanGordon SB, Seavey J, Sofinowski TM, Ramadan M, Abdullah S, Buffington CA, Hurst RE. Abnormalities in expression of structural, barrier and differentiation related proteins, and chondroitin sulfate in feline and human interstitial cystitis. J Urol. 2015;194:571–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Monastyrskaya K, Sánchez-Freire V, Hashemi Gheinani A, Klumpp DJ, Babiychuk EB, Draeger A, Burkhard FC. miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome. Am J Pathol. 2013;182:431–48.

    Article  CAS  PubMed  Google Scholar 

  21. Jhang JF, Kuo HC. Pathomechanism of interstitial cystitis/bladder pain syndrome and mapping the heterogeneity of disease. Int Neurourol J. 2016;20(Suppl 2):S95–104.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Shie JH, Kuo HC. Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int. 2011;108(2 Pt 2):E136–41.

    PubMed  Google Scholar 

  23. Shie JH, Liu HT, Kuo HC. Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. Urology. 2012;79(484):e7–13.

    Google Scholar 

  24. Yu WR, Jiang YH, Jhang JF, Kuo HC. Use of urinary cytokine and chemokine levels for identifying bladder conditions and predicting treatment outcomes in patients with interstitial cystitis/bladder pain syndrome. Biomedicines. 2022;10:1149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. •• Yu WR, Jhang JF, Ho HC, Jiang YH, Lee CL, Hsu YH, Kuo HC. Cystoscopic hydrodistention characteristics provide clinical and long-term prognostic features of interstitial cystitis after treatment. Sci Rep. 2021;11:455. Patients with IC/BPS subgroups had distinct bladder characteristics and treatment outcomes. The patients with high maximal bladder capacity and low glomerulation grade after hydrodistention had more medical comorbidities but a significantly higher rate of satisfactory treatment outcome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Whitmore KE, Fall M, Sengiku A, Tomoe H, Logadottir Y, Kim YH. Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome. Int J Urol. 2019;26(Suppl 1):26–34.

    Article  PubMed  Google Scholar 

  27. Lee JD, Lee MH. Increased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor associated with glomerulation formation in patients with interstitial cystitis. Urology. 2011;78(971):e11–5.

    Google Scholar 

  28. Akiyama Y, Miyakawa J, O’Donnell MA, Kreder KJ, Luo Y, Maeda D, Ushiku T, Kume H, Homma Y. Overexpression of HIF1-α in Hunner lesions of interstitial cystitis: pathophysiological implications. J Urol. 2022;207:635–46.

    Article  PubMed  Google Scholar 

  29. Jiang YH, Jhang JF, Kuo HC. Urinary oxidative stress biomarker levels might be useful in identifying functional bladder disorders in women with frequency and urgency syndrome. J Clin Med. 2023;12:2336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. • Wu ZS, Luo HL, Chuang YC, Lee WC, Wang HJ, Chancellor MB. Platelet lysate therapy attenuates hypoxia induced apoptosis in human uroepithelial SV-HUC-1 cells through regulating the oxidative stress and mitochondrial-mediated intrinsic apoptotic pathway. Biomedicines. 2023;11:935. PRP injection can attenuate hypoxia-induced urothelial apoptosis and regulate oxidative stress condition in IC/BPS

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. •• Jhang JF, Hsu YH, Peng CW, Jiang YH, Ho HC, Kuo HC. Epstein-Barr virus as a potential etiology of persistent bladder inflammation in human interstitial cystitis/bladder pain syndrome. J Urol. 2018;200:590–6. EB virus infection was demonstrated to be one of the pathogenesis in patients with IC/BPS, especially in patients with HIC

    Article  PubMed  Google Scholar 

  32. •• Jhang JF, Liu CD, Hsu YH, Chen CC, Chen HC, Jiang YH, Wu WC, Peng CW, Kuo HC. EBV infection mediated BDNF expression is associated with bladder inflammation in interstitial cystitis/bladder pain syndrome with Hunner's lesion. J Pathol. 2023;259:276–90. The first study to provide insights into the mechanisms underlying the involvement of EBV-infected B cells in HIC pathogenesis. Anti-viral therapy can reduce bladder pain and improve bladder condition in HIC and NHIC with high glomerulation grade.

    Article  CAS  PubMed  Google Scholar 

  33. Peng L, Jin X, Li BY, Zeng X, Liao BH, Jin T, Chen JW, Gao XS, Wang W, He Q, Chen G, Gong LN, Shen H, Wang KJ, Li H, Luo DY. Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis. Signal Transduct Target Ther. 2022;7:161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Antunes-Lopes T, Vale L, Coelho AM, Silva C, Rieken M, Geavlete B, Rashid T, Rahnama'i SM, Cornu JN, Marcelissen T, EAU Young Academic Urologists (YAU) Functional Urology Working Group. The role of urinary microbiota in lower urinary tract dysfunction: a systematic review. Eur Urol Focus. 2020;6:361–9.

    Article  PubMed  Google Scholar 

  35. Yıldırım S, Shoskes D, Kulkarni S, Laguna P. Urinary microbiome in uncomplicated and interstitial cystitis: is there any similarity? World J Urol. 2020;38:2721–31.

    Article  PubMed  Google Scholar 

  36. Kim J, De Hoedt A, Wiggins E, Haywood K, Jin P, Greenwood B, Narain NR, Tolstikov V, Bussberg V, Barbour KE, Kiebish MA, Freedland SJ, Anger JT. Diagnostic utility of serum and urinary metabolite analysis in patients with interstitial cystitis/painful bladder syndrome. Urology. 2021;157:85–92.

    Article  PubMed  Google Scholar 

  37. Parsons CL. The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology. 2007;69(4 Suppl):9–16.

    Article  PubMed  Google Scholar 

  38. Kuo HC, Jiang YH, Tsai YC, Kuo YC. 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. 2016;35:609–14.

    Article  CAS  PubMed  Google Scholar 

  39. Jhang JF, Lin TY, Kuo HC. Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-a prospective clinical trial. Neurourol Urodyn. 2019;38:703–9.

    Article  CAS  PubMed  Google Scholar 

  40. • Chuang YC, Meng E, Chancellor M, Kuo HC. Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome-a prospective, multicenter, randomized, double-blind, placebo-controlled study. Neurourol Urodyn. 2020;39:1505–14. LESW applied on the bladder could attenuate the bladder pain visual analog score, but was not superior to the placebo effect.

    Article  PubMed  Google Scholar 

  41. Jhang JF, Jiang YH, Hsu YH, Ho HC, Birder LA, Lin TY, Kuo HC. Improved urothelial cell proliferation, cytoskeleton and barrier function protein expression in the patients with interstitial cystitis/bladder pain syndrome after intravesical platelet-rich plasma injection. Int Neurourol J. 2022;26(Suppl 1):S57–567.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ko KJ, Cho WJ, Lee YS, Choi J, Byun HJ, Lee KS. Comparison of the efficacy between transurethral coagulation and transurethral resection of Hunner lesion in interstitial cystitis/bladder pain syndrome patients: a prospective randomized controlled trial. Eur Urol. 2020;77:644–51.

    Article  PubMed  Google Scholar 

  43. Chung SD, Wang CC, Kuo HC. Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain. Neurourol Urodyn. 2014;33:1207–11.

    Article  CAS  PubMed  Google Scholar 

  44. Wu SY, Kuo HC. A real-world experience with augmentation enterocystoplasty- high patient satisfaction with high complication rates. Neurourol Urodyn. 2018;37:744–50.

    Article  PubMed  Google Scholar 

  45. Yu WR, Jhang JF, Chen BY, Ou SR, Li HM, Kuo HC. Multimodal treatment with cognitive behavioral therapeutic intervention plus bladder treatment Is more effective than monotherapy for patients with interstitial cystitis/bladder pain syndrome - a randomized clinical trial. J Clin Med. 2022;11:6221.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Hoke TP, Goldstein H, Saks EK, Vakili B. Hydrodistention of the bladder for the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Neurourol Urodyn. 2017;36:784–6.

    Article  PubMed  Google Scholar 

  47. Kirk PS, Santiago-Lastra Y, Qin Y, Stoffel JT, Clemens JQ, Cameron AP. The effects of cystoscopy and hydrodistention on symptoms and bladder capacity in interstitial cystitis/bladder pain syndrome. Neurourol Urodyn. 2018;37:2002–7.

    Article  PubMed  Google Scholar 

  48. Grinberg K, Sela Y, Nissanholtz-Gannot R. New insights about chronic pelvic pain syndrome (CPPS). Int J Environ Res Public Health. 2020;17:3005.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Overman EL, Rivier JE, Moeser AJ. CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PLoS One. 2012;7:e39935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Jhang JF, Birder LA, Jiang YH, Hsu YH, Ho HC, Kuo HC. Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome. Sci Rep. 2019;9:19169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Brünahl CA, Klotz SGR, Dybowski C, Albrecht R, Höink J, Fisch M, Ketels G, Löwe B. Physiotherapy and combined cognitive-behavioural therapy for patients with chronic pelvic pain syndrome: results of a non-randomised controlled feasibility trial. BMJ Open. 2021;11:e053421.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. J Urol. 2001;166:2226–31.

    Article  CAS  PubMed  Google Scholar 

  53. FitzGerald MP, Payne CK, Lukacz ES, Yang CC, Peters KM, Chai TC, Nickel JC, Hanno PM, Kreder KJ, Burks DA, Mayer R, Kotarinos R, Fortman C, Allen TM, Fraser L, Mason-Cover M, Furey C, Odabachian L, Sanfield A, et al. Interstitial Cystitis Collaborative Research Network. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness. J Urol. 2012;187:2113–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. •• Jhang JF, Hsu YH, Ho HC, Jiang YH, Lee CL, Yu WR, Kuo HC. Possible association between bladder wall morphological changes on computed tomography and bladder-centered interstitial cystitis/bladder pain syndrome. Biomedicines. 2021;9:1306. Bladder wall thickening on CT was correlated with clinical phenotypes of IC/BPS, including histopathological findings. Focal or diffuse bladder wall thickening on CT indicates the presence of chronic bladder wall inflammation and fibrosis.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Hillelsohn JH, Rais-Bahrami S, Friedlander JI, Okhunov Z, Kashan M, Rosen L, Moldwin RM. Fulguration for Hunner ulcers: long-term clinical outcomes. J Urol. 2012;188:2238–41.

    Article  PubMed  Google Scholar 

  56. Ryu J, Pak S, Song M, Chun JY, Hong S, Choo MS. Elimination of Hunner's ulcers by fulguration in patients with interstitial cystitis: is it effective and long lasting? Korean J Urol. 2013;54:767–71.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Chennamsetty A, Khourdaji I, Goike J, Killinger KA, Girdler B, Peters KM. Electrosurgical management of Hunner ulcers in a referral center’s interstitial cystitis population. Urology. 2015;85:74–8.

    Article  PubMed  Google Scholar 

  58. Morales A, Emerson L, Nickel JC, Lundie M. Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. J Urol. 1996;156:45–8.

    Article  CAS  PubMed  Google Scholar 

  59. Lai MC, Kuo YC, Kuo HC. Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: a comparative randomized assessment of different regimens. Int J Urol. 2013;20:203–7.

    Article  CAS  PubMed  Google Scholar 

  60. Pyo JS, Cho WJ. Systematic review and meta-analysis of intravesical hyaluronic acid and hyaluronic acid/chondroitin sulfate instillation for interstitial cystitis/painful bladder syndrome. Cell Physiol Biochem. 2016;39:1618–25.

    Article  CAS  PubMed  Google Scholar 

  61. Lin CJ, Liu CK, Hsieh HY, Chen MJ, Tsai CP. Changes in cystoscopic findings after intravesical hyaluronic acid instillation therapy in patients with interstitial cystitis. Diagnostics (Basel). 2022;12:2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wyndaele JJJ, Riedl C, Taneja R, Lovász S, Ueda T, Cervigni M. GAG replenishment therapy for bladder pain syndrome/interstitial cystitis. Neurourol Urodyn. 2019;38:535–44.

    Article  PubMed  Google Scholar 

  63. Jiang YH, Liao CH, Kuo HC. Current and potential urological applications of botulinum toxin A. Nat Rev Urol. 2015;12:519–33.

    Article  CAS  PubMed  Google Scholar 

  64. 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;58:360–5.

    Article  CAS  PubMed  Google Scholar 

  65. Giannantoni A, Gubbiotti M, Bini V. Botulinum neurotoxin A intravesical injections in interstitial cystitis/bladder painful syndrome: a systematic review with meta-analysis. Toxins (Basel). 2019;11:510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kuo HC, Chancellor MB. Comparison of intravesical botulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis/painful bladder syndrome. BJU Int. 2009;104:657–61.

    Article  CAS  PubMed  Google Scholar 

  67. Wang HJ, Yu WR, Ong HL, Kuo HC. Predictive factors for a satisfactory treatment outcome with intravesical botulinum toxin A injection in patients with interstitial cystitis/bladder pain syndrome. Toxins (Basel). 2019;11:676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pinto R, Lopes T, Costa D, Barros S, Silva J, Silva C, Cruz C, Dinis P, Cruz F. Ulcerative and nonulcerative forms of bladder pain syndrome/interstitial cystitis do not differ in symptom intensity or response to onabotulinum toxin A. Urology. 2014;83:1030–4.

    Article  PubMed  Google Scholar 

  69. Lee CL, Kuo HC. Intravesical botulinum toxin a injections do not benefit patients with ulcer type interstitial cystitis. Pain Physician. 2013;16:109–16.

    PubMed  Google Scholar 

  70. Janicki JJ, Chancellor MB, Kaufman J, Gruber MA, Chancellor DD. Potential effect of liposomes and liposome-encapsulated botulinum toxin and tacrolimus in the treatment of bladder dysfunction. Toxins (Basel). 2016;8:81.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Rappaport YH, Zisman A, Jeshurun-Gutshtat M, Gerassi T, Hakim G, Vinshtok Y, Stav K. Safety and feasibility of intravesical instillation of botulinum toxin-A in hydrogel-based slow-release delivery system in patients with interstitial cystitis-bladder pain syndrome: a pilot study. Urology. 2018;114:60–5.

    Article  PubMed  Google Scholar 

  72. Chuang YC, Kuo HC. A Prospective, Multicenter, Double-blind, randomized trial of bladder instillation of liposome formulation onabotulinumtoxinA for interstitial cystitis/bladder pain syndrome. J Urol. 2017;198:376–82.

    Article  CAS  PubMed  Google Scholar 

  73. Rawls WF, Cox L, Rovner ES. Dimethyl sulfoxide (DMSO) as intravesical therapy for interstitial cystitis/bladder pain syndrome: a review. Neurourol Urodyn. 2017;36(7):1677–84.

    Article  PubMed  Google Scholar 

  74. Shiga KI, Hirano K, Nishimura J, Niiro N, Naito S, Kanaide H. Dimethyl sulphoxide relaxes rabbit detrusor muscle by decreasing the Ca2+ sensitivity of the contractile apparatus. Br J Pharmacol. 2007;151(7):1014–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yoshimura N, Homma Y, Tomoe H, Otsuka A, Kitta T, Masumori N, Akiyama Y, Niimi A, Mitsui T, Nanri M, Namima T, Takei M, Yamaguchi A, Sekiguchi Y, Kajiwara M, Kobayashi S, Ameda K, Ohashi Y, Sakamoto S, et al. Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: a multicenter, randomized, double-blind, placebo-controlled, clinical study. Int J Urol. 2021;28(5):545–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Moss NP, Chill HH, Sand PK, Chang C, Goldberg RP, Gafni-Kane A. A prospective, randomized trial comparing intravesical dimethyl sulfoxide (DMSO) to bupivacaine, triamcinolone, and heparin (BTH), for newly diagnosed interstitial cystitis/painful bladder syndrome (IC/PBS). Neurourol Urodyn. 2023;42(3):615–22.

    Article  CAS  PubMed  Google Scholar 

  77. Laviana A, Jellison F, Kim JH. Sacral neuromodulation for refractory overactive bladder, interstitial cystitis, and painful bladder syndrome. Neurosurg Clin N Am. 2014;25(1):33–46.

    Article  PubMed  Google Scholar 

  78. Greig J, Mak Q, Furrer MA, Sahai A, Raison N. Sacral neuromodulation in the management of chronic pelvic pain: a systematic review and meta-analysis. Neurourol Urodyn. 2023;42(4):822–36.

    Article  PubMed  Google Scholar 

  79. Padilla-Fernández B, Hernández-Hernández D, Castro-Díaz DM. Current role of neuromodulation in bladder pain syndrome/interstitial cystitis. Ther Adv Urol. 2022;14:17562872221135941.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Tutolo M, Ammirati E, Heesakkers J, Kessler TM, Peters KM, Rashid T, Sievert KD, Spinelli M, Novara G, Van der Aa F, De Ridder D. efficacy and safety of sacral and percutaneous tibial neuromodulation in non-neurogenic lower urinary tract dysfunction and chronic pelvic pain: a systematic review of the literature. Eur Urol. 2018;73(3):406–18.

    Article  PubMed  Google Scholar 

  81. Rahnama'i MS, Marcelissen T, Apostolidis A, Veit-Rubin N, Schurch B, Cardozo L, Dmochowski R. The efficacy of botulinum toxin A and sacral neuromodulation in the management of interstitial cystitis (IC)/bladder pain syndrome (BPS), what do we know? ICI-RS 2017 think thank, Bristol. Neurourol Urodyn. 2018;37(S4):S99–S107.

    Article  PubMed  Google Scholar 

  82. Ke QS, Jhang JF, Lin TY, Ho HC, Jiang YH, Hsu YH, Kuo HC. Therapeutic potential of intravesical injections of platelet-rich plasma in the treatment of lower urinary tract disorders due to regenerative deficiency. Ci Ji Yi Xue Za Zhi. 2019;31:135–43.

    PubMed  Google Scholar 

  83. •• Jiang YH, Kuo YC, Jhang JF, Lee CL, Hsu YH, Ho HC, Kuo HC. Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis. Sci Rep. 2020;10:15218. Repeated intravesical injections of PRP improve bladder pain and clinical symptoms of IC/BPS and decrease the urinary level of nerve growth factor, matrix metalloproteinase-13, and vascular endothelial growth factor.

    Article  PubMed  PubMed Central  Google Scholar 

  84. • Lee YK, Jiang YH, Jhang JF, Ho HC, Kuo HC. Changes in the ultrastructure of the bladder urothelium in patients with interstitial cystitis after intravesical injections of platelet-rich plasma. Biomedicines. 2022;10:1182. Repeated PRP injection can improve the ultrastructural morphology of the urothelium in IC/BPS patients, including urothelium cell layers, umbrella cell integrity, umbrella cell surface uroplakin plaque, tight junctions between adjacent umbrella cells, lysed organelles, and decreased inflammatory cell infiltration.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hung MJ, Tsai CP, Ying TH, Chen GD, Su HL, Tseng CJ. Improved symptoms and signs of refractory interstitial cystitis in women after intravesical Nanofat plus platelet-rich plasma grafting: a pilot study. J Chin Med Assoc. 2022;85:730–5.

    Article  CAS  PubMed  Google Scholar 

  86. Chen PY, Cheng JH, Wu ZS, Chuang YC. New frontiers of extracorporeal shock wave medicine in urology from bench to clinical studies. Biomedicines. 2022;10:675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wang HJ, Tyagi P, Lin TK, Huang CC, Lee WC, Chancellor MB, Chuang YC. Low energy shock wave therapy attenuates mitochondrial dysfunction and improves bladder function in HCl induced cystitis in rats. Biomed J. 2022;45:482–90.

    Article  CAS  PubMed  Google Scholar 

  88. Jhang LS, Hsieh WC, Huang TX, Chou YC, Lo TS, Liang CC, Lin YH. Use of low-intensity extracorporeal shock wave therapy in the management of interstitial cystitis/bladder pain syndrome patients: a thirty case study in a tertiary medical center. Neurourol Urodyn. 2023;42:65–72.

    Article  CAS  PubMed  Google Scholar 

  89. Chuang YC, Huang TL, Tyagi P, Huang CC. Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using low energy shock waves. J Urol. 2016;196:599–608.

    Article  CAS  PubMed  Google Scholar 

  90. • Jiang YH, Jhang JF, Lee YK, Kuo HC. Low-energy shock wave plus intravesical instillation of botulinum toxin A for interstitial cystitis/bladder pain syndrome: pathophysiology and preliminary result of a novel minimally invasive treatment. Biomedicines. 2022;10:396. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on IC/BPS. The result provides evidence for the treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Blaivas JG, Weiss JP, Desai P, Flisser AJ, Stember DS, Stahl PJ. Long-term followup of augmentation enterocystoplasty and continent diversion in patients with benign disease. J Urol. 2005;173:1631–4.

    Article  PubMed  Google Scholar 

  92. Linn JF, Hohenfellner M, Roth S, Dahms SE, Stein R, Hertle L, Thüroff JW, Hohenfellner R. Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution. J Urol. 1998;159(3):774–8.

    Article  CAS  PubMed  Google Scholar 

  93. Castillo OA, Miranda-Utrera N. Laparoscopic cystectomy and intracorporeal continent urinary diversion (Mainz II) in treatment for interstitial cystitis. Actas Urol Esp. 2014;38(3):200–4.

    Article  CAS  PubMed  Google Scholar 

  94. Peng CH, Jhang JF, Shie JH, Kuo HC. Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical OnabotulinumtoxinA injections combined with hydrodistention for patients with interstitial cystitis--clinical results and immunohistochemistry analysis. Urology. 2013;82(1452):e1–6.

    Google Scholar 

  95. Tooke K, Girard B, Vizzard MA. Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis. Am J Physiol Renal Physiol. 2019;317:F43–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Furuta A, Suzuki Y, Igarashi T, Koike Y, Kimura T, Egawa S, Yoshimura N. Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome. Int J Urol. 2019;26(Suppl 1):35–40.

    Article  CAS  PubMed  Google Scholar 

  97. Perkins ME, Girard BM, Campbell SE, Vizzard MA. Imatinib mesylate reduces voiding frequency in female mice with acute cyclophosphamide-induced cystitis. Front Syst Neurosci. 2022;16:867875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Di Lena M, Tolls V, Kelly KL, Nickel JC. Mirabegron as adjuvant treatment for patients with interstitial cystitis/bladder pain syndrome. Can Urol Assoc J. 2018;12:E100–4.

    Article  PubMed  Google Scholar 

  99. • Jiang YH, Jhang JF, Birder LA, Kuo HC. Sensory receptor, inflammatory, and apoptotic protein expression in the bladder urothelium of patients with different subtypes of interstitial cystitis/bladder pain syndrome. Int J Mol Sci. 2023;24:820. The results of this study revealed that IC/BPS patients with frequency and bladder pain complaints have higher levels of urothelial sensory receptors, and inflammatory and pro-apoptotic proteins. The sensory receptors might be a treatment target for refractory IC/BPS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Werneburg GT, Keslar KS, Gotwald P, Doolittle J, Vij SC, Lee BH, Shoskes DA. Neuroinflammatory gene expression analysis reveals potential novel mediators and treatment targets in interstitial cystitis with Hunner lesions. Transl Androl Urol. 2021;10:4100–9.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Chen CL, Kao CC, Yang MH, Fan GY, Cherng JH, Tsao CW, Wu ST, Cha TL, Meng E. a novel intravesical dextrose injection improves lower urinary tract symptoms on interstitial cystitis/bladder pain syndrome. Front Pharmacol. 2021;12:755615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Nursing, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan

    Wan-Ru Yu

  2. Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien, Taiwan

    Yuan-Hong Jiang, Jia-Fong Jhang & Hann-Chorng Kuo

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  1. Wan-Ru Yu
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  4. Hann-Chorng Kuo
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Yu, WR., Jiang, YH., Jhang, JF. et al. Bladder Pain Syndrome Associated with Interstitial Cystitis: Recent Research and Treatment Options. Curr Bladder Dysfunct Rep 18, 389–400 (2023). https://doi.org/10.1007/s11884-023-00722-6

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