Skip to main content

Physiopathology of Overactive Bladder

  • Chapter
  • First Online:
Non-Neurogenic Bladder Dysfunctions

Abstract

Overactive bladder syndrome (OAB) is a common disorder with significant impact on quality of life. According to the International Continence Society (ICS), OAB is characterized by urgency, with or without urgency urinary incontinence, usually with increased daytime frequency and nocturia. To date, this condition has a poorly defined pathophysiology. The present chapter provides an overview on multiple factors and mechanisms that might be involved in OAB pathophysiology.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21:167–78.

    Article  PubMed  Google Scholar 

  2. Abrams P, Artibani W, Cardozo L, et al. Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn. 2009;28(4):287.

    Article  PubMed  Google Scholar 

  3. Milsom I, Kaplan SA, Coyne KS, et al. Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: results from EpiLUTS. Urology. 2012;80(1):90–6.

    Article  PubMed  Google Scholar 

  4. Wyndaele JJ, Van Meel TD, De Wachter S. Detrusor overactivity. Does it represent a difference if patients feel the involuntary contractions? J Urol. 2004;172(5 Pt 1):1915–8.

    Article  PubMed  Google Scholar 

  5. Malone-Lee J, Henshaw DJ, Cummings K. Urodynamic verification of an overactive bladder is not a prerequisite for antimuscarinic treatment response. BJU Int. 2003;92(4):415–7.

    Article  CAS  PubMed  Google Scholar 

  6. Matharu G, Donaldson MM, McGrother CW, et al. Relationship between urinary symptoms reported in a postal questionnaire and urodynamic diagnosis. Neurourol Urodyn. 2005;24(2):100–5.

    Article  CAS  PubMed  Google Scholar 

  7. Hashim H, Abrams P. Is the bladder a reliable witness for predicting detrusor overactivity? J Urol. 2006;175(1):191–4; discussion 194–5.

    Article  CAS  PubMed  Google Scholar 

  8. Michel MC, Chapple CR. Basic mechanisms of urgency: preclinical and clinical evidence. Eur Urol. 2009;56(2):298–307.

    Article  PubMed  Google Scholar 

  9. Shefchyk SJ. Sacral spinal interneurones and the control of urinary bladder and urethral striated sphincter muscle function. J Physiol. 2001;533:57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yoshimura N, Chancellor MB. Neurophysiology of lower urinary tract function and dysfunction. Rev Urol. 2003;5(Suppl 8):S3–S10.

    PubMed  PubMed Central  Google Scholar 

  11. de Groat WC, Booth AM. Synaptic transmission in pelvic ganglia. In: Maggi CA, editor. The autonomic nervous system. London: Harwood Academic Publishers; 1993. p. 291–347.

    Google Scholar 

  12. Andersson KE. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev. 1993;45:253–308.

    Google Scholar 

  13. Thor KB, Morgan C, et al. Organization of afferent and efferent pathways in the pudendal nerve of the female cat. J Comp Neurol. 1989;288(2):263–79.

    Article  CAS  PubMed  Google Scholar 

  14. Andersson KE, Pehrson R. CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention. Drugs. 2003;63(23):2595–611.

    Article  CAS  PubMed  Google Scholar 

  15. Chancellor MB, de Groat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol. 1999;162(1):3–11.

    Article  CAS  PubMed  Google Scholar 

  16. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9(6):453–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. de Groat WC, Booth AM, Yoshimura N. Neurophysiology of micturition and its modification in animal models of human disease. In: Maui CA, editor. The autonomic nervous system. London: Harwood Academic Publishers; 1993. p. 227–89.

    Google Scholar 

  18. Rick BF, Holstege A. Two pontine micturition centers in the cat are not interconnected directly: implications for the central organization of micturition. J Comp Neural. 1993;402:209–18.

    Google Scholar 

  19. de Groat WC. A neurologic basis for the overactive bladder. Urology. 1997;50:36–52; discussion 53–6.

    Article  PubMed  Google Scholar 

  20. Yokoyama O, Yoshiyama M, Namiki M, et al. Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion. Am J Phys. 1999;276(4):R935–42.

    CAS  Google Scholar 

  21. Campeau L, Soler R, Andersson KE. Bladder dysfunction and parkinsonism: current pathophysiological understanding and management strategies. Curr Urol Rep. 2011;12(6):396–403.

    Article  PubMed  Google Scholar 

  22. Sakakibara R, Tateno F, Kishi M, et al. Pathophysiology of bladder dysfunction in Parkinson’s disease. Neurobiol Dis. 2012;46(3):565–71.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. Brady CM, Apostolidis A, Yiangou Y, et al. P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol. 2004;46(2):247–53.

    Article  CAS  PubMed  Google Scholar 

  25. Apostolidis A, Fowler CJ. The use of botulinum neurotoxin type a (BoNTA) in urology. J Neural Transm. 2008;115(4):593–605.

    Article  CAS  PubMed  Google Scholar 

  26. O’Reilly BA, Kosaka AH, Knight GF, et al. P2X receptors and their role in female idiopathic detrusor instability. J Urol. 2002;167:157–64.

    Article  PubMed  Google Scholar 

  27. Brading AF. A myogenic basis for the overactive bladder. Urology. 1997;50(6A Suppl):57–67; discussion 68–73.

    Article  CAS  PubMed  Google Scholar 

  28. Brading AF, Turner WH. The unstable bladder: towards a common mechanism. Br J Urol. 1994;73(1):3–8.

    Article  CAS  PubMed  Google Scholar 

  29. Levin RM, Longhurst PA, Monson FC, et al. Effect of bladder outlet obstruction on the morphology, physiology, and pharmacology of the bladder. Prostate Suppl. 1990;3:9–26.

    Article  CAS  PubMed  Google Scholar 

  30. Gosling JA, Kung LS, Dixon JS, et al. Correlation between the structure and function of the rabbit urinary bladder following partial outlet obstruction. J Urol. 2000;163:1349–56.

    Article  CAS  PubMed  Google Scholar 

  31. Malmqvist U, Arner A, Uvelius B. Contractile and cytoskeletal proteins in smooth muscle during hypertrophy and its reversal. Am J Phys. 1991;260:C1085–93.

    Article  CAS  Google Scholar 

  32. Sjuve R, Haase H, Morano I, et al. Contraction kinetics and myosin isoform composition in smooth muscle from hypertrophied rat urinary bladder. J Cell Biochem. 1996;63:86–93.

    Article  CAS  PubMed  Google Scholar 

  33. Levin RM, Levin SS, Zhao Y. Cellular and molecular aspects of bladder hypertrophy. Eur Urol. 1997;32(Suppl 1):15–21.

    PubMed  Google Scholar 

  34. Gabella G, Uvelius B. Urinary bladder of rat: fine structure of normal and hypertrophic musculature. Cell Tissue Res. 1990;262:67–79.

    Article  CAS  PubMed  Google Scholar 

  35. Turner WH, Brading AF. Smooth muscle of the bladder in the normal and the diseased state: pathophysiology, diagnosis and treatment. Pharmacol Ther. 1997;75:77–110.

    Article  CAS  PubMed  Google Scholar 

  36. Charlton RG, Morley AR, Chambers P, et al. Focal changes in nerve, muscle and connective tissue in normal and unstable human bladder. BJU Int. 1999;84:953–60.

    Article  CAS  PubMed  Google Scholar 

  37. Mills IW, Greenland JE, McMurray G, et al. Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation. J Urol. 2000;163:646–51.

    Article  CAS  PubMed  Google Scholar 

  38. Steers WD. Pathophysiology of overactive bladder and urge urinary incontinence. Rev Urol. 2002;4(Suppl 4):S7–S18.

    PubMed  PubMed Central  Google Scholar 

  39. Elbadawi A, Hailemariam S, Yalla SV, et al. Structural basis of geriatric voiding dysfunction. VII. Prospective ultrastructural/urodynamic evaluation of its natural evolution. J Urol. 1997;157:1814–22.

    Article  CAS  PubMed  Google Scholar 

  40. Yoshida M, Miyamae K, Iwashita H, et al. Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology. 2004;63:17–23.

    Article  PubMed  Google Scholar 

  41. Wang HZ, Lee SW, Day NS. Gap junction channel activity in cultured human bladder smooth muscle cell pairs: gating and unitary conductances. Urology. 2001;57(suppl 1):111–2.

    Article  CAS  PubMed  Google Scholar 

  42. Neuhaus J, Weimann A, Stolzenburg JU, et al. Smooth muscle cells from human urinary bladder express connexin 43 in vivo and in vitro. World J Urol. 2002;20:250–4.

    Article  CAS  PubMed  Google Scholar 

  43. Miyazato M, Sugaya K, Nishijima S, et al. Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats. Int Urol Nephrol. 2009;41(4):815–21.

    Article  CAS  PubMed  Google Scholar 

  44. Hegde SS. Muscarinic receptors in the bladder: from basic research to therapeutics. Br J Pharmacol. 2006;147:S80–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bing W, Chang S, Hypolite JA, et al. Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for rho kinase. Am J Physiol Renal Physiol. 2003;285(5):F990–7.

    Article  PubMed  Google Scholar 

  46. Rajasekaran M, Wilkes N, Kuntz S, et al. Rho-kinase inhibition suppresses bladder hyperactivity in spontaneously hypertensive rats. Neurourol Urodyn. 2005;24(3):295–300.

    Article  CAS  PubMed  Google Scholar 

  47. Maggi CA, Santicioli P, Parlani M, et al. The presence of mucosa reduces the contractile response of the Guinea-pig urinary bladder to substance P. J Pharm Pharmacol. 1987;39:653–5.

    Article  CAS  PubMed  Google Scholar 

  48. Birder LA, de Groat WC. Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol. 2007;4:46–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Apodaca G. The uroepithelium: not just a passive barrier. Traffic. 2004;5:117–28.

    Article  CAS  PubMed  Google Scholar 

  50. Wang EC, Lee JM, Ruiz WG, et al. ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. J Clin Invest. 2005;115(9):2412–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lewis SA, Lewis JR. Kinetics of urothelial ATP release. Am J Physiol Renal Physiol. 2006;291(2):F332–40.

    Article  CAS  PubMed  Google Scholar 

  52. Elneil S, Skepper JN, Kidd EJ, et al. Distribution of P2X(1) and P2X(3) receptors in the rat and human urinary bladder. Pharmacology. 2001;63(2):120–8.

    Article  CAS  PubMed  Google Scholar 

  53. Vlaskovska M, Kasakov L, Rong W, et al. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001;21(15):5670–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn. 2007;26(6 Suppl):934–47.

    Article  CAS  PubMed  Google Scholar 

  55. Khera M, Somogyi GT, Kiss S, et al. Botulinum toxin a inhibits ATP release from bladder urothelium after chronic spinal cord injury. Neurochem Int. 2004;45(7):987–93.

    Article  CAS  PubMed  Google Scholar 

  56. Sugaya K, Nishijima S, Kadekawa K, et al. Relationship between lower urinary tract symptoms and urinary ATP in patients with benign prostatic hyperplasia or overactive bladder. Biomed Res. 2009;30(5):287–94.

    Article  CAS  PubMed  Google Scholar 

  57. Bschleipfer T, Schukowski K, Weidner W, et al. Expression and distribution of cholinergic receptors in the human urothelium. Life Sci. 2007;80(24–25):2303–7.

    Article  CAS  PubMed  Google Scholar 

  58. Yoshida M, Inadome A, Maeda Y, et al. Non-neuronal cholinergic system in human bladder urothelium. Urology. 2006;67(2):425–30.

    Article  PubMed  Google Scholar 

  59. Araki I, Du S, Kamiyama M, et al. Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction. Urology. 2004;64(6):1255–60.

    Article  PubMed  Google Scholar 

  60. Liu HT, Kuo HC. Increased expression of transient receptor potential vanilloid subfamily 1 in the bladder predicts the response to intravesical instillations of resiniferatoxin in patients with refractory idiopathic detrusor overactivity. BJU Int. 2007;100(5):1086–90.

    CAS  PubMed  Google Scholar 

  61. Apostolidis A, Brady CM, Yiangou Y, et al. Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology. 2005;65(2):400–5.

    Article  PubMed  Google Scholar 

  62. Steers WD, Kolbeck S, Creedon D, et al. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest. 1991;88(5):1709–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Baker SA, Hatton WJ, Han J, et al. Role of TREK-1 potassium channel in bladder overactivity after partial bladder outlet obstruction in mouse. J Urol. 2010;183(2):793–800.

    Article  CAS  PubMed  Google Scholar 

  64. Darblade B, Behr-Roussel D, Oger S, et al. Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder. Urology. 2006;68(2):442–8.

    Article  PubMed  Google Scholar 

  65. Kita M, Yunoki T, Takimoto K, et al. Effects of bladder outlet obstruction on properties of Ca2+-activated K+ channels in rat bladder. Am J Physiol Regul Integr Comp Physiol. 2010;298(5):R1310–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Semins MJ, Chancellor MB. Diagnosis and management of patients with overactive bladder syndrome and abnormal detrusor activity. Nat Clin Pract Urol. 2004;1(2):78–84.

    Article  PubMed  Google Scholar 

  67. Dupont MC, Spitsbergen JM, Kim KB, et al. Histological and neurotrophic changes triggered by varying models of bladder inflammation. J Urol. 2001;166:1111–8.

    Article  CAS  PubMed  Google Scholar 

  68. Archer JSNAMS. Solvay resident essay award. Relationship between estrogen, serotonin, and depression. Menopause. 1999;6(1):71–8.

    CAS  PubMed  Google Scholar 

  69. Nishizawa S, Benkefalt C, Young SN, et al. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997;94(10):5308–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hanna-Mitchell AT, Robinson D, Cardozo L, et al. Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014. Neurol Urodyn. 2016;35:299–303.

    Article  CAS  Google Scholar 

  71. Lee KC. Changes of muscarinic receptors and connexin-43 expression as a mechanism of overactive bladder in ovariectomized rats. World J Urol. 2015;33:1875–9.

    Article  CAS  PubMed  Google Scholar 

  72. Petros PE, Woodman PJ. The integral theory of continence. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19:35–40.

    Article  PubMed  Google Scholar 

  73. Wolfe F, Russell IJ, Vipraio G, et al. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol. 1997;24:555–9.

    CAS  PubMed  Google Scholar 

  74. Zorn BH, Montgomery H, Pieper K, et al. Urinary incontinence and depression. J Urol. 1999;162:82–4.

    Article  CAS  PubMed  Google Scholar 

  75. Read KE, Sanger GJ, Ramage AG. Evidence for the involvement of central 5-HT7 receptors in the micturition reflex in anaesthetized female rats. Br J Pharmacol. 2003;140:53–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. de Groat WC. Influence of central serotoninergic mechanisms on lower urinary tract function. Urology. 2002;59(5 Suppl 1):30–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Enrico Finazzi Agrò .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Finazzi Agrò, E., Pastore, S., Ambrosi Grappelli, V.M., Carilli, M. (2021). Physiopathology of Overactive Bladder. In: Balzarro, M., Li Marzi, V. (eds) Non-Neurogenic Bladder Dysfunctions. Urodynamics, Neurourology and Pelvic Floor Dysfunctions. Springer, Cham. https://doi.org/10.1007/978-3-030-57393-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-57393-5_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-57392-8

  • Online ISBN: 978-3-030-57393-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics