Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2025.029

Effects of intravesical cocktail instillation on outcomes and serum pain factors of patients with bladder pain syndrome

Yunpeng Jia1, Yuanning Zhang2, Bo Wang1, Junjia Shi3
1 Department of Urology, TCM Hospital of Gansu Province, Lanzhou 730050, Gansu Province, China
2 Department of Urology, Renhuai People's Hospital, Renhuai 564500, Guizhou Province, China
3 Department of Urology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou 325000, Zhejiang Province, China

Aims: We aimed to assess the effects of intravesical cocktail instillation on the outcomes and serum pain factors of patients with bladder pain syndrome (BPS).

Methods: The clinical data of 86 female BPS patients hospitalized between March 2017 and March 2024 were collected for retrospective analysis. All patients were treated with oral medication (amitriptyline) + local intravesical instillation of drugs, and then assigned to a control group (sodium hyaluronate intravesical instillation) and a research group [intravesical instillation of dimethyl sulfoxide (DMSO) + chondroitin sulfate (CS) + low-molecular-weight heparin (LMWH) cocktail].

Results: The research group (n=43) had lower urination frequency in 24 h, Pelvic Pain and Urgency/Frequency Patient Symptom Scale score, and O'Leary-Sant interstitial cystitis symptom index and interstitial cystitis problem index, as well as larger single urination volume than those of the control group (n=43) after 3 and 6 months of treatment (P<0.05). In the serum, the levels of substance P (SP), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2), neuropeptide Y (NPY), β-endorphin (β-EP), and dopamine (DA) declined in the two groups after 1 month of treatment in comparison to the pre-treatment levels. The levels of SP, 5-HT, PGE2, and NPY were lower, while the levels of β-EP and DA were higher in the research group than those in the control group (P<0.05).

Conclusion: The intravesical instillation of DMSO + CS + LMWH cocktail is superior in long-term outcomes. It is more conducive to improving the levels of serum pain factors, with a good safety profile and without increasing adverse reactions.

Keywords: bladder pain syndrome, cocktail, intravesical instillation, outcome

Received: April 27, 2025; Revised: September 3, 2025; Accepted: October 6, 2025; Prepublished online: November 11, 2025 

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References

  1. Chen A, Shahiyan RH, Anger JT. Interstitial Cystitis/Bladder Pain Syndrome Treatment: A Systematic Review of Sexual Health Outcomes. Sex Med Rev2022;10(1):71-6. Go to original source...
  2. Borrego-Jimenez PS, Flores-Fraile J, Padilla-Fernández BY, Valverde-Martinez S, Gómez-Prieto A, Márquez-Sánchez MT, Mirón-Canelo JA, Lorenzo-Gómez MF. Improvement in Quality of Life with Pelvic Floor Muscle Training and Biofeedback in Patients with Painful Bladder Syndrome/Interstitial Cystitis. J Clin Med 2021;10(4):862. Go to original source...
  3. 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(1):60-7. Go to original source...
  4. Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 2015;193(5):1545-53. Go to original source...
  5. Cox A, Golda N, Nadeau G, Curtis Nickel J, Carr L, Corcos J, Teichman J. CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Can Urol Assoc J 2016;10(5-6):E13655. Go to original source...
  6. van Ginkel C, Baars C, Heesakkers J, Martens F, Janssen D. Study protocol of a multicentre double-blind RCT, comparing a traditional RCT with an aggregated N-of-1 trial: GAG therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI study). BMJ Open 2023;13(4):e068546. Go to original source...
  7. Guo W, Liu H, Zhang J, Zhang J, Wang F, Zhang P, Yang Y. Preparation and characterization of a novel composite acellular matrix/hyaluronic acid thermosensitive hydrogel for interstitial cystitis/bladder pain syndrome. J Biomed Mater Res A 2024;112(3):449-62. Go to original source...
  8. 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 and hypersensitive bladder syndrome. Int J Urol 2009;16(7):597-615. Go to original source...
  9. Ford AC, Wright-Hughes A, Alderson SL, Ow PL, Ridd MJ, Foy R, Bianco G, Bishop FL, Chaddock M, Cook H, Cooper D, Fernandez C, Guthrie EA, Hartley S, Herbert A, Howdon D, Muir DP, Nath T, Newman S, Smith T, Taylor CA, Teasdale EJ, Thornton R, Farrin AJ, Everitt HA; ATLANTIS trialists. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023;402(10414):1773-85. Go to original source...
  10. Tesfaye S, Sloan G, Petrie J, White D, Bradburn M, Julious S, Rajbhandari S, Sharma S, Rayman G, Gouni R, Alam U, Cooper C, Loban A, Sutherland K, Glover R, Waterhouse S, Turton E, Horspool M, Gandhi R, Maguire D, Jude EB, Ahmed SH, Vas P, Hariman C, McDougall C, Devers M, Tsatlidis V, Johnson M, Rice ASC, Bouhassira D, Bennett DL, Selvarajah D; OPTION-DM trial group. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022;400(10353):680-90. Go to original source...
  11. Shen SH, Peng L, Zeng X, Zhang J, Shen H, Luo DY. Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis: A Randomized Clinical Trial. JAMA Netw Open 2024;7(4):e244880. Go to original source...
  12. Ghaith AF, Radwan MH, Rashed Taha M, Elbendary MA, Al Damhogy ME, Hagras AM. Evaluation of pain and quality of life after hyaluronic acid instillation in addition to botulinum toxin-A injection in women with refractory Interstitial Cystitis/Painful Bladder Syndrome: A pilot study. Arch Itali Urol Androl 2022;94(4):447-50. Go to original source...
  13. Yoshimura N, Uno T, Sasaki M, Ohinata A, Nawata S, Ueda T. The O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically useful indicator of treatment outcome in patients with interstitial cystitis/bladder pain syndrome with Hunner lesions: A post hoc analysis of the Japanese phase III trial of KRP-116D, 50% dimethyl sulfoxide solution. Int J Urol 2022;29(4):289-96. Go to original source...
  14. Huang MC, Hsieh CH, Chang WC, Chang ST, Lee MS. Assessment of treatment outcomes of interstitial cystitis with hydrodistention and bladder training by O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices. Taiwan J Obstet Gynecol 2018;57(5):718-21. Go to original source...
  15. Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, Koziol JA. 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):573-78. Go to original source...
  16. 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, Muraki O, Shishido T, Kageyama S, Kokura K, Okazoe H, Yamanishi T, Watanabe T, Uno T, Ohinata A, Ueda T. 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. Go to original source...
  17. Poletajew S, Brzózka MM, Krajewski W, Kamecki H, Nyk Ł, Kryst P. Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review. Pain Ther 2024;13:1-22. Go to original source...
  18. Danacioglu YO, Erol B, Ozkanli S, Yildirim A, Atis RG, Silay MS, Caskurlu T. Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis. Int Neurourol J 2021;25(1):42-50. Go to original source...
  19. Sogutdelen E, Citamak B. Efficacy of intravesical cocktail therapy with or without dimethyl sulphoxide in interstitial cystitis. Cent European J Urol 2022;75(3):299-304.
  20. Konthapakdee N, Grundy L, O'Donnell T, Garcia-Caraballo S, Brierley SM, Grundy D, Daly DM. Serotonin exerts a direct modulatory role on bladder afferent firing in mice. J Physiol 2019;597(21):5247-64. Go to original source...
  21. Hokanson JA, Langdale CL, Milliken PH, Sridhar A, Grill WM. Effects of intravesical prostaglandin E2 on bladder function are preserved in capsaicin-desensitized rats. Am J Physiol Renal Physiol 2021;320(2):F212-23. Go to original source...
  22. Nanri M, Matsuo M. Early experience of intravesical instillation of dimethyl sulfoxide 50% solution for hunner type interstitial cystitis in a clinic. Nihon Hinyokika Gakkai Zasshi 2022;113(4):122-7. Go to original source...
  23. Obara K, Matsuoka Y, Iwata N, Abe Y, Ikegami Y, Fujii A, Yoshioka K, Tanaka Y. Dimethyl Sulfoxide Enhances Acetylcholine-Induced Contractions in Rat Urinary Bladder Smooth Muscle by Inhibiting Acetylcholinesterase Activities. Biol Pharm Bull 2023;46(2):354-58. Go to original source...
  24. Kocatürk H, Atasoy N, Bedir F, Altay MS, Demirdöđen ŢO, Koç E, Yilmaz S. Questionnaire-guided evaluation of the effectiveness of long-term intravesical 0,2% chondroitin sulfate therapy in interstitial cystitis. Int Urogynecol J 2021;32(5):1293-8. Go to original source...
  25. Di XP, Luo DY, Jin X, Zhao WY, Li H, Wang KJ. Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis. Int Urogynecol J 2021;32(5):1129-41. Go to original source...
  26. Liu L, Xue L, Zhou J, Dong B, Li Y, Li Z, Dong Y, Han C. Evaluation of clinical efficacy of pelvic ultrasound monitoring combined with scale scoring in the treatment of interstitial cystitis by intravesical instillation regimen combined with hydrodistention and transurethral fulguration. BMC Urol 2025;25(1):117. Go to original source...
  27. Wein AJ. Re: Long-Term Outcomes of Intravesical Dimethyl Sulfoxide/Heparin/Hydrocortisone Therapy for Interstitial Cystitis/Bladder Pain Syndrome. J Urol 2018;199(4):897-8. Go to original source...

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