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Botulinum Toxin for Neurogenic and Non-neurogenic Bladder Pain

  • Neurogenic Bladder (C Powell, Section Editor)
  • Published:
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Abstract

Purpose of Review

The use of botulinum toxin in managing urinary incontinence has been well established. Given the expanding indications for this agent for several neuromuscular disorders, its role in managing the symptoms associated with interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic pelvic pain syndrome (CPPS) is evolving. In this review article, we examine the current literature on outcomes after botulinum toxin injection in patients with these conditions, as well as recent developments in mechanism of delivery.

Recent Findings

The change in pain scores after injection in IC/BPS patients is inconsistent, as it has been used in combination with and without other interventions, such as hydrodistension. Pooled studies favor the use of botulinum toxin, but the findings are not significant to justify its use as a first-line treatment for IC/BPS. The initial hope that botulinum toxin would improve CPPS by addressing hypertonic pelvic floor dysfunction has been tempered by several studies showing no significant reduction in pain scores after injection compared to placebo.

Summary

Several studies have shown there to be a therapeutic benefit for pain management in IC/BPS, particularly in those without Hunner’s lesions. Meta-analysis suggests that higher dose may further improve pain scores, but side effects of urinary retention may limit its applicability. This effect does not appear to be dependent on how the toxin is injected (trigone vs non-trigone). Future use of intravesical liposomes to deliver botulinum toxin shows promise in administration of the agent in a non-invasive manner.

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References

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

  1. Hanno PM, Erickson D, Moldwin R, Faraday MM, Association AU. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545–53. https://doi.org/10.1016/j.juro.2015.01.086.

    Article  PubMed  Google Scholar 

  2. Suskind AM, Berry SH, Ewing BA, Elliott MN, Suttorp MJ, Clemens JQ. The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. J Urol. 2013;189(1):141–5. https://doi.org/10.1016/j.juro.2012.08.088.

    Article  PubMed  Google Scholar 

  3. Warren JW, Howard FM, Cross RK, et al. Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology. 2009;73(1):52–7. https://doi.org/10.1016/j.urology.2008.06.031.

    Article  PubMed  Google Scholar 

  4. Talati A, Ponniah K, Strug LJ, Hodge SE, Fyer AJ, Weissman MM. Panic disorder, social anxiety disorder, and a possible medical syndrome previously linked to chromosome 13. Biol Psychiatry. 2008;63(6):594–601. https://doi.org/10.1016/j.biopsych.2007.07.021.

    Article  CAS  PubMed  Google Scholar 

  5. Ahangari A. Prevalence of chronic pelvic pain among women: an updated review. Pain Physician. 2014;17(2):E141-7.

    Article  Google Scholar 

  6. Latthe P, Mignini L, Gray R, Hills R, Khan K. Factors predisposing women to chronic pelvic pain: systematic review. BMJ. 2006;332(7544):749–55. https://doi.org/10.1136/bmj.38748.697465.55.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Purwar B, Khullar V. Use of botulinum toxin for chronic pelvic pain. Womens Health (Lond). 2016;12(3):293–6. https://doi.org/10.2217/whe-2016-0007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hanno PM, Burks DA, Clemens JQ, et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185(6):2162–70. https://doi.org/10.1016/j.juro.2011.03.064.

    Article  PubMed  Google Scholar 

  9. Fall M, Baranowski AP, Elneil S, et al. EAU guidelines on chronic pelvic pain. Eur Urol. 2010;57(1):35–48. https://doi.org/10.1016/j.eururo.2009.08.020.

    Article  PubMed  Google Scholar 

  10. Scaglione F. 2016 Conversion Ratio between Botox®, Dysport®, and Xeomin® in Clinical Practice. Toxins (Basel) 8(3) https://doi.org/10.3390/toxins8030065

  11. Dolly JO, O’Connell MA. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol. 2012;12(1):100–8. https://doi.org/10.1016/j.coph.2011.11.001.

    Article  CAS  PubMed  Google Scholar 

  12. Rummel A. The long journey of botulinum neurotoxins into the synapse. Toxicon. 2015;107(Pt A):9–24. https://doi.org/10.1016/j.toxicon.2015.09.009.

    Article  CAS  PubMed  Google Scholar 

  13. Antonucci F, Corradini I, Fossati G, Tomasoni R, Menna E, Matteoli M. SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions. Front Synaptic Neurosci. 2016;8:7. https://doi.org/10.3389/fnsyn.2016.00007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bleakman D, Alt A, Nisenbaum ES. Glutamate receptors and pain. Semin Cell Dev Biol. 2006;17(5):592–604. https://doi.org/10.1016/j.semcdb.2006.10.008.

    Article  CAS  PubMed  Google Scholar 

  15. Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE. Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int. 2008;101(3):366–70. https://doi.org/10.1111/j.1464-410X.2007.07312.x.

    Article  CAS  PubMed  Google Scholar 

  16. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26(5):785–93. https://doi.org/10.1016/j.neuro.2005.01.017.

    Article  CAS  PubMed  Google Scholar 

  17. Bittencourt da Silva L, Karshenas A, Bach FW, Rasmussen S, Arendt-Nielsen L, Gazerani P. Blockade of glutamate release by botulinum neurotoxin type A in humans: a dermal microdialysis study. Pain Res Manag. 2014;19(3):126–32. https://doi.org/10.1155/2014/410415.

    Article  PubMed  Google Scholar 

  18. Burnstock G. Purinergic signalling in the urinary tract in health and disease. Purinergic Signal. 2014;10(1):103–55. https://doi.org/10.1007/s11302-013-9395-y.

    Article  CAS  PubMed  Google Scholar 

  19. Hanna-Mitchell AT, Wolf-Johnston AS, Barrick SR, et al. Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium. Neurourol Urodyn. 2015;34(1):79–84. https://doi.org/10.1002/nau.22508.

    Article  CAS  PubMed  Google Scholar 

  20. Khera M, Somogyi GT, Kiss S, Boone TB, Smith CP. Botulinum toxin A inhibits ATP release from bladder urothelium after chronic spinal cord injury. Neurochem Int. 2004;45(7):987–93. https://doi.org/10.1016/j.neuint.2004.06.001.

    Article  CAS  PubMed  Google Scholar 

  21. Apostolidis A, Popat R, Yiangou Y, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174(3):977–82. https://doi.org/10.1097/01.ju.0000169481.42259.54 (discussion 982-3).

    Article  CAS  PubMed  Google Scholar 

  22. Schulte-Baukloh H, Priefert J, Knispel HH, Lawrence GW, Miller K, Neuhaus J. Botulinum toxin A detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity: a single-blind study. Urology. 2013;81(5):1052–7. https://doi.org/10.1016/j.urology.2012.12.021.

    Article  PubMed  Google Scholar 

  23. Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB. Intravesical botulinum toxin A administration inhibits COX-2 and EP4 expression and suppresses bladder hyperactivity in cyclophosphamide-induced cystitis in rats. Eur Urol. 2009;56(1):159–66. https://doi.org/10.1016/j.eururo.2008.05.007.

    Article  CAS  PubMed  Google Scholar 

  24. Shie JH, Liu HT, Wang YS, Kuo HC. Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome. BJU Int. 2013;111(4):638–46. https://doi.org/10.1111/j.1464-410X.2012.11466.x.

    Article  CAS  PubMed  Google Scholar 

  25. Peck MW, Smith TJ, Anniballi F, et al. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature. Toxins (Basel). 2017;9(1)https://doi.org/10.3390/toxins9010038

  26. Chen CL, Meng E. Can Botulinum Toxin A Play A Role In Treatment Of Chronic Pelvic Pain Syndrome In Female Patients?-Clinical and Animal Evidence. Toxins (Basel). 2020;12(2)https://doi.org/10.3390/toxins12020110

  27. 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(3)https://doi.org/10.3390/toxins8030081

  28. Atassi MZ. Basic immunological aspects of botulinum toxin therapy. Mov Disord. 2004;19(Suppl 8):S68-84. https://doi.org/10.1002/mds.20020.

    Article  PubMed  Google Scholar 

  29. Kazerooni R, Broadhead C. Cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia. Am J Health Syst Pharm. 2015;72(4):301–7. https://doi.org/10.2146/ajhp140276.

    Article  PubMed  Google Scholar 

  30. Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol. 1973;12(12):924–7.

    CAS  PubMed  Google Scholar 

  31. Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988;139(5):919–22. https://doi.org/10.1016/s0022-5347(17)42717-0.

    Article  CAS  PubMed  Google Scholar 

  32. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131–9. https://doi.org/10.1016/j.juro.2012.01.125.

    Article  CAS  PubMed  Google Scholar 

  33. Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742–50. https://doi.org/10.1016/j.eururo.2011.07.002.

    Article  CAS  PubMed  Google Scholar 

  34. Nitti VW, Dmochowski R, Herschorn S, et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186–93. https://doi.org/10.1016/j.juro.2012.12.022.

    Article  CAS  PubMed  Google Scholar 

  35. Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64(2):249–56. https://doi.org/10.1016/j.eururo.2013.04.001.

    Article  CAS  PubMed  Google Scholar 

  36. 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(5):657–61. https://doi.org/10.1111/j.1464-410X.2009.08495.x.

    Article  CAS  PubMed  Google Scholar 

  37. G K. Randomized controlled trial for efficacy of botulinum toxin type a in treatment of patients suffering bladder pain syndrome/interstitial cystitis with Hunner's lesions: preliminary results. Journal of Urology. 2012;187:335–6.

  38. Manning J, Dwyer P, Rosamilia A, Colyvas K, Murray C, Fitzgerald E. A multicentre, prospective, randomised, double-blind study to measure the treatment effectiveness of abobotulinum A (AboBTXA) among women with refractory interstitial cystitis/bladder pain syndrome. Int Urogynecol J. 2014;25(5):593–9. https://doi.org/10.1007/s00192-013-2267-8.

    Article  PubMed  Google Scholar 

  39. Gottsch HP, Miller JL, Yang CC, Berger RE. A pilot study of botulinum toxin for interstitial cystitis/painful bladder syndrome. Neurourol Urodyn. 2011;30(1):93–6. https://doi.org/10.1002/nau.20946.

    Article  CAS  PubMed  Google Scholar 

  40. 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(5):609–14. https://doi.org/10.1002/nau.22760.

    Article  CAS  PubMed  Google Scholar 

  41. Pinto RA, Costa D, Morgado A, et al. Intratrigonal OnabotulinumtoxinA Improves Bladder Symptoms and Quality of Life in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Pilot, Single Center, Randomized, Double-Blind, Placebo Controlled Trial. J Urol. 2018;199(4):998–1003. https://doi.org/10.1016/j.juro.2017.10.018.

    Article  CAS  PubMed  Google Scholar 

  42. Lee CL, Kuo HC. Intravesical botulinum toxin a injections do not benefit patients with ulcer type interstitial cystitis. Pain Physician. 2013;16(2):109–16.

    PubMed  Google Scholar 

  43. Evans RJ, Overholt T, Colaco M, Walker SJ. Injection location does not impact botulinum toxin A efficacy in interstitial cystitis/bladder pain syndrome patients. Can J Urol. 2020;27(1):10125–9.

    PubMed  Google Scholar 

  44. Jiang YH, Jhang JF, Lee CL, Kuo HC. Comparative study of efficacy and safety between bladder body and trigonal intravesical onabotulinumtoxina injection in the treatment of interstitial cystitis refractory to conventional treatment-A prospective, randomized, clinical trial. Neurourol Urodyn. 2018;37(4):1467–73. https://doi.org/10.1002/nau.23475.

    Article  CAS  PubMed  Google Scholar 

  45. • Lee CL, Kuo HC. Long-Term Efficacy and Safety of Repeated Intravescial OnabotulinumtoxinA Injections Plus Hydrodistention in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome. Toxins (Basel). 2015;7(10):4283–93. https://doi.org/10.3390/toxins7104283. (This prospective study is the only one to report sustained long-term effectiveness of BoNT-A injections in reducing pain and improving bladder capacity.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gao Y, Liao L. Intravesical injection of botulinum toxin A for treatment of interstitial cystitis/bladder pain syndrome: 10 years of experience at a single center in China. Int Urogynecol J. 2015;26(7):1021–6. https://doi.org/10.1007/s00192-015-2631-y.

    Article  PubMed  Google Scholar 

  47. Shim SR, Cho YJ, Shin IS, Kim JH. Efficacy and safety of botulinum toxin injection for interstitial cystitis/bladder pain syndrome: a systematic review and meta-analysis. Int Urol Nephrol. 2016;48(8):1215–27. https://doi.org/10.1007/s11255-016-1295-y.

    Article  CAS  PubMed  Google Scholar 

  48. Parsons BA, Goonewardene S, Dabestani S, et al. The benefits and harms of botulinum toxin-A in the treatment of chronic pelvic pain syndromes: a systematic review by the European Association of Urology Chronic Pelvic Pain Panel. Eur Urol Focus. 2021. https://doi.org/10.1016/j.euf.2021.01.005.

    Article  PubMed  Google Scholar 

  49. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol. 1996;87(3):321–7. https://doi.org/10.1016/0029-7844(95)00458-0.

    Article  CAS  PubMed  Google Scholar 

  50. Srinivasan AK, Kaye JD, Moldwin R. Myofascial dysfunction associated with chronic pelvic floor pain: management strategies. Curr Pain Headache Rep. 2007;11(5):359–64. https://doi.org/10.1007/s11916-007-0218-0.

    Article  PubMed  Google Scholar 

  51. Moldwin RM, Fariello JY. Myofascial trigger points of the pelvic floor: associations with urological pain syndromes and treatment strategies including injection therapy. Curr Urol Rep. 2013;14(5):409–17. https://doi.org/10.1007/s11934-013-0360-7.

    Article  PubMed  Google Scholar 

  52. Jarvis SK, Abbott JA, Lenart MB, Steensma A, Vancaillie TG. Pilot study of botulinum toxin type A in the treatment of chronic pelvic pain associated with spasm of the levator ani muscles. Aust N Z J Obstet Gynaecol. 2004;44(1):46–50. https://doi.org/10.1111/j.1479-828X.2004.00163.x.

    Article  PubMed  Google Scholar 

  53. Abbott JA, Jarvis SK, Lyons SD, Thomson A, Vancaille TG. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet Gynecol. 2006;108(4):915–23. https://doi.org/10.1097/01.AOG.0000237100.29870.cc.

    Article  PubMed  Google Scholar 

  54. • Adelowo A, Hacker MR, Shapiro A, Modest AM, Elkadry E. Botulinum toxin type A (BOTOX) for refractory myofascial pelvic pain. Female Pelvic Med Reconstr Surg. 2013;19(5):288–92. https://doi.org/10.1097/SPV.0b013e3182989fd8. (Authors demonstrated that BoNT-A with TPI can reduce pelvic pain though there are temporary adverse effects.)

    Article  PubMed  PubMed Central  Google Scholar 

  55. Halder GE, Scott L, Wyman A, et al. Botox combined with myofascial release physical therapy as a treatment for myofascial pelvic pain. Investig Clin Urol. 2017;58(2):134–9. https://doi.org/10.4111/icu.2017.58.2.134.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dessie SG, Von Bargen E, Hacker MR, Haviland MJ, Elkadry E. A randomized, double-blind, placebo-controlled trial of onabotulinumtoxin A trigger point injections for myofascial pelvic pain. Am J Obstet Gynecol. 2019;221(5):517.e1-517.e9. https://doi.org/10.1016/j.ajog.2019.06.044.

    Article  CAS  Google Scholar 

  57. Bartley J, Nguyen L, Hasenau D, et al. 2019 PD20–09 Onobotuliumtoxin A versus Kenalog for intravaginal trigger point injections in the treatment of chronic pelvic pain. https://doi.org/10.1097/01.JU.0000555741.75359.15

  58. Chuang YC, Lee WC, Chiang PH. Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol. 2009;182(4):1393–400. https://doi.org/10.1016/j.juro.2009.06.024.

    Article  CAS  PubMed  Google Scholar 

  59. Peters KM, Hasenau D, Killinger KA, Chancellor MB, Anthony M, Kaufman J. Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation. Int Urol Nephrol. 2014;46(12):2291–5. https://doi.org/10.1007/s11255-014-0828-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kuo HC, Liu HT, Chuang YC, Birder LA, Chancellor MB. Pilot study of liposome-encapsulated onabotulinumtoxina for patients with overactive bladder: a single-center study. Eur Urol. 2014;65(6):1117–24. https://doi.org/10.1016/j.eururo.2014.01.036.

    Article  CAS  PubMed  Google Scholar 

  61. • Chuang YC, Kaufmann JH, Chancellor DD, Chancellor MB, Kuo HC. Bladder instillation of liposome encapsulated onabotulinumtoxina improves overactive bladder symptoms: a prospective, multicenter, double-blind, randomized trial. J Urol. 2014;192(6):1743–9. https://doi.org/10.1016/j.juro.2014.07.008. (This well-designed multi-centered RCT of lipo-BoNT in refractory OAB patients is an exciting as it promises the next technological advancement for intravesical BoNT-A. Patient’s frequency improved while suffering from no side effects that commonly plagues BoNT-A injections. If results in larger trials continue to show efficacy, the role of lipo-BoNT may surpass that of BoNT-A injections.)

    Article  CAS  PubMed  Google Scholar 

  62. Kuo H-C. https://clinicaltrials.gov/ct2/show/NCT02247557.

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  1. Oakland University William Beaumont School of Medicine, Beaumont Hospital, 3535 W. 13 Mile Rd. Suite 438, Royal Oak, MI, 48073, USA

    Ly Hoang Roberts & Jason P. Gilleran

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Roberts, L.H., Gilleran, J.P. Botulinum Toxin for Neurogenic and Non-neurogenic Bladder Pain. Curr Bladder Dysfunct Rep 17, 38–47 (2022). https://doi.org/10.1007/s11884-021-00640-5

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