Skip to main content

Pathophysiology of Overactive Bladder: Current Understanding


Purpose of Review

To describe leading hypotheses surrounding the pathophysiology of overactive bladder (OAB), as well as describe the mechanisms of action of current treatment options for OAB.

Recent Findings

There are two main underlying mechanisms of OAB: mechanisms with increased sensory (afferent) activity and mechanisms with abnormal management of afferent signals. In the former category, increased afferent activity is thought to be related either to abnormalities in the urothelium receptor function and neurotransmitter release (urothelium-based hypothesis) or to abnormalities in myocyte excitability (myogenic hypothesis). In the latter category, OAB is thought to be related to the dysregulation of the handling of afferent signals (neurogenic hypothesis).


OAB is complex and multifactorial in its etiology. Further research should be undertaken to better characterize the pathophysiology of the disorder, so that more targeted treatments can be developed.

This is a preview of subscription content, access via your institution.


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

  1. 1.

    Haylen BT, De Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, et al. An International Urogynecological Association / International Continence Society joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29:4–20.

    PubMed  Google Scholar 

  2. 2.

    van Kerrebroeck P, Abrams P, Chaikin D. The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21:179–83.

    Article  PubMed  Google Scholar 

  3. 3.

    Banakhar MA, Al-Shaiji TF, Hassouna MM. Pathophysiology of overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct. 2012;975–82.

  4. 4.

    Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;37–49.

  5. 5.

    Wein AJ, Rovner ES, Staskin DR, Andersson KE, Ouslander JG. Definition and epidemiology of overactive bladder. Urology. 2002;7–12.

  6. 6.

    Dmochowski RR, Newman DK. Impact of overactive bladder on women in the United States: results of a national survey. Curr Med Res Opin. 2007;23:65–76. Available from:

    Article  PubMed  Google Scholar 

  7. 7.

    Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;327–36.

  8. 8.

    Hashim H, Abrams P. Is the bladder a reliable witness for predicting detrusor overactivity? J Urol. 2006;175:191–4.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    • Chapple C. Chapter 2: pathophysiology of neurogenic detrusor overactivity and the symptom complex of “overactive bladder”. Neurourol Urodyn. 2014;33:S6–13. This comprehensive review delineates the pathophysiology of neurogenic DO , citing recent evidence to support each of the proposed hypotheses.

    Article  PubMed  Google Scholar 

  10. 10.

    • Abrams P, Khoury S. et al. Incontinence: ICUD-EAU. 2013;261–359. This book is the ultimate resource on incontinence, summarizing the latest scientific evidence and current theories on OAB.

  11. 11.

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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    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 

  13. 13.

    Frazier EP, Peters SLM, Braverman AS, Ruggieri MR, Michel MC. Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and β3-adrenoceptors. Naunyn. Schmiedebergs. Arch Pharmacol. 2008;449–62.

  14. 14.

    • Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9:453–66. This review summarizes recent findings regarding the sensory and motor mechanisms and neural pathways in normal micturition.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Wiseman OJ, Fowler CJ, Landon DN. The role of the human bladder lamina propria myofibroblast. BJU Int. 2003;91:89–93.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Morrison J. The activation of bladder wall afferent nerves. Exp Physiol. 1999;84:131–6.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Andersson KE. Bladder activation: afferent mechanisms. Urology. 2002;59:43–50.

    Article  PubMed  Google Scholar 

  18. 18.

    • Yoshida M. The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: pathophysiology and pharmacotherapy of overactive bladder. J Pharmacol Sci. 2010;112:128–34. This is a comprehensive review of the pharmacology of the lower urinary tract.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    • Brading AF. A myogenic basis for the overactive bladder. Urology. 1997;57–73. This review proposes that the underlying mechanism for OAB ultimately lies within the myocytes, regardless of etiology.

  20. 20.

    Brading A, Turner W. The unstable bladder: towards a common mechanism. Br J Urol. 1994;73:3–8.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Drake MJ, Mills IW, Gillespie JI. Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function. Lancet. 2001;358:401–3.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Mills IW, Greenland JE, McMurray G, McCoy R, Ho KM, Noble JG, 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.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Coolsaet BLRA, Van Duyl WA, Van O, Bossagh P, De Bakker HV. New concepts in relation to urge and detrusor activity. Neurourol Urodyn. 1993;12:463–71.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Downie JW, Armour JA. Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder. Can J Physiol Pharmacol. 1992;70:1457–67.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Gillespie JI, Van Koeveringe GA, De Wachter SG, De Vente J. On the origins of the sensory output from the bladder: the concept of afferent noise. BJU Int. 2009;1324–33.

  26. 26.

    Drake MJ, Harvey IJ, Gillespie JI, Van Duyl WA. Localized contractions in the normal human bladder and in urinary urgency. BJU Int. 2005;95:1002–5.

    Article  PubMed  Google Scholar 

  27. 27.

    Neuhaus J, Pfeiffer F, Wolburg H, Horn LC, Dorschner W. Alterations in connexin expression in the bladder of patients with urge symptoms. BJU Int. 2005;96:670–6.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Phé V, Behr-Roussel D, Oger-Roussel S, Rouprêta M, Chartier-Kastlera E, Lebretc T, et al. Involvement of connexins 43 and 45 in functional mechanism of human detrusor overactivity in neurogenic bladder. Urology. 2013;82:982–3.

    Article  PubMed  Google Scholar 

  29. 29.

    Andersson KE. Detrusor myocyte activity and afferent signaling. Neurourol Urodyn. 2010;97–106.

  30. 30.

    McCloskey KD. Bladder interstitial cells: an updated review of current knowledge. Acta Physiol (Oxf). 2013;207:7–15.

    CAS  Article  Google Scholar 

  31. 31.

    Juszczak K, Maciukiewicz P, Drewa T, Thor PJ. Cajal-like interstitial cells as a novel target in detrusor overactivity treatment: true or myth? Cent Eur J Urol. 2013;413–7.

  32. 32.

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

  33. 33.

    • De Groat WC. Neurologic basis for the overactive bladder. Urology. 1997;36–52. The manuscript gives a detailed overview of the central neural control of micturition, explaining how disruptions in the mechanism lead to OAB.

  34. 34.

    Drake M, Emmanuel A. Neurologic urinary and faecal incontinence: ICUD-EAU. 2013.

  35. 35.

    Lucio AC, Campos RM, Perissinotto MC, Miyaoka R, Damasceno BP, D’Ancona CA. Pelvic floor muscle training in the treatment of lower urinary tract dysfunction in women with multiple sclerosis. Neurourol Urodyn. 2010;29:1410–3.

    Article  PubMed  Google Scholar 

  36. 36.

    McClurg D, Lowe-Strong A, Ashe R. The benefits of pelvic floor muscle training in people with multiple sclerosis and lower urinary tract dysfunction. J Assoc Chart Physiother Women’s Heal. 2008;103:21–8.

    Google Scholar 

  37. 37.

    Abrams P, Andersson K-E. Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007;100:987–1006.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Abrams P, Andersson K-E, Buccafusco JJ, Chapple C, de Groat WC, Fryer AD, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006;148:565–78.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Finney SM, Andersson KE, Gillespie JI, Stewart LH. Antimuscarinic drugs in detrusor overactivity and the overactive bladder syndrome: motor or sensory actions? BJU Int. 2006; 503–7.

  40. 40.

    De Laet K, De Wachter S, Wyndaele JJ. Systemic oxybutynin decreases afferent activity of the pelvic nerve of the rat: new insights into the working mechanism of antimuscarinics. Neurourol Urodyn. 2006;25:156–61.

    Article  PubMed  Google Scholar 

  41. 41.

    Iijima K, De Wachter S, Wyndaele JJ. Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve. Eur Urol. 2007;52:842–9.

    Article  PubMed  Google Scholar 

  42. 42.

    Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4’-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007;321:642–7.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Petkov GV. Role of potassium ion channels in detrusor smooth muscle function and dysfunction. Nat Rev Urol. 2012;9:30–40.

    CAS  Article  Google Scholar 

  44. 44.

    D’Agostino G, Condino AM, Calvi P. Involvement of β3-adrenoceptors in the inhibitory control of cholinergic activity in human bladder: direct evidence by [3H]-acetylcholine release experiments in the isolated detrusor. Eur J Pharmacol. 2015;758:115–22.

    Article  PubMed  Google Scholar 

  45. 45.

    Leng WW, Chancellor MB. How sacral nerve stimulation neuromodulation works. Urol Clin North Am. 2005;11–8.

  46. 46.

    Birder L, De Groat W, Mills I, Morrison J, Thor K, Drake M. Neural control of the lower urinary tract: peripheral and spinal mechanisms. Neurourol Urodyn. 2010;128–39.

  47. 47.

    Peters KM, MacDiarmid SA, Wooldridge LS, Leong FC, Shobeiri SA, Rovner ES, et al. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009;182:1055–61.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Peters KM, Carrico DJ, Perez-Marrero RA, Khan AU, Wooldridge LS, Davis GL, et al. Randomized trial of percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. 2010;183:1438–43.

    Article  PubMed  Google Scholar 

  49. 49.

    Finazzi-Agrò E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P. Percutaneous tibial nerve stimulation effects on detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial. J Urol. 2010;184:2001–6.

    Article  PubMed  Google Scholar 

  50. 50.

    Siegel S, Noblett K, Mangel J, Giebling T, Sutherland SE, Bird ET. Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6 months in subjects with mild symptoms of overactive bladder. Neurourol Urodyn. 2015;34:224–30.

    Article  PubMed  Google Scholar 

  51. 51.

    van Kerrebroeck PEV, van Voskuilen AC, Heesakkers JPFA, Lycklama Á, Nijholt AAB, Siegel S, et al. Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study. J Urol. 2007;178:2029–34.

    Article  PubMed  Google Scholar 

  52. 52.

    Hassouna MM, Siegel SW, Nÿeholt AA, Elhilali MM, van Kerrebroeck PE, Das AK, et al. Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety. J Urol. 2000;163:1849–54.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    López Ramos H, Torres Castellanos L, Ponce Esparza I, Jaramillo A, Rodríguez A, Moreno Bencardino C. Management of overactive bladder with OnabotulinumtoxinA: systematic review and meta-analysis. Urology. 2016.

  54. 54.

    Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D. Botulinum toxin injections for adults with overactive bladder syndrome. Cochrane Database Syst Rev. 2011;CD005493.

  55. 55.

    Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, 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;189:2186–93.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Gormley EA, Lightner DJ, Faraday M, Vasavada SP. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015;193:1572–80.

    Article  PubMed  Google Scholar 

  57. 57.

    Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected Botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;644–50.

  58. 58.

    Drake MJ. Mechanisms of action of intravesical botulinum treatment in refractory detrusor overactivity. BJU Int. 2008;11–6.

  59. 59.

    Cruz F. Mechanisms involved in new therapies for overactive bladder. Urology. 2004;65–73.

  60. 60.

    Nitti VW, Ginsberg D, Sievert K-D, Sussman D, Radomski S, Sand P, et al. Durable efficacy and safety of long-term onabotulinumtoxinA treatment in patients with overactive bladder syndrome: final results of a 3.5-year study. J Urol. 2016;196:791–800.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Judy M. Choi.

Ethics declarations

Conflict of Interest

Dr. Palmer and Dr. Choi declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Overactive Bladder

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Palmer, C.J., Choi, J.M. Pathophysiology of Overactive Bladder: Current Understanding. Curr Bladder Dysfunct Rep 12, 74–79 (2017).

Download citation


  • Overactive bladder
  • Urinary frequency
  • Urinary urgency
  • Urinary incontinence