Current Bladder Dysfunction Reports

, Volume 13, Issue 4, pp 267–273 | Cite as

Shared Pathophysiology of Detrusor Overactivity and Detrusor Underactivity

  • Henry Collier Wright
  • Elizabeth Timbrook BrownEmail author
Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Reconstructed Bladder Function & Dysfunction


Purpose of Review

Detrusor overactivity (DO) and the associated symptom complex of overactive bladder (OAB) is well-studied with many treatment options. In contrast, detrusor underactivity (DU) and its associated symptom complex, underactive bladder (UAB), is poorly understood. Researchers have proposed explanations that link OAB and UAB with a common pathophysiology. The purpose of this review is to examine concepts and recent underlying research supporting a shared pathophysiology of DO and DU.

Recent Findings

In 2014, Dr. Michael Chancellor proposed “The Overactive Bladder Progression to Underactive Bladder Hypothesis.” Since then, researchers have conducted several animal and human studies to examine the pathophysiology of OAB and UAB. These studies, which highlight this shared pathophysiology, can be categorized broadly into neurogenic, myogenic, urothelial dysfunction, and idiopathic etiologies. Autonomous bladder micromotions are another proposed mechanism of shared OAB and UAB pathophysiology.


UAB is poorly understood in comparison to OAB, yet the concept of a shared pathophysiology could shed light into future research, technology, and pharmacologic interventions to adequately manage patients with these conditions.


Underactive bladder Overactive bladder Detrusor overactivity Detrusor underactivity Pathophysiology 


Compliance with Ethical Standards

Conflict of Interest

Dr. Wright and Dr. Brown 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.


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

  1. 1.
    •• Chancellor MB. The overactive bladder progression to underactive bladder hypothesis. Int Urol Nephrol. 2014;46(Suppl 1):S23–7. This is the original article discussing the hypothesis of the shared pathophysiology of OAB and UAB. Dr. Chancellor highlights his observations and the available research that supports his hypothesis. To the author’s knowledge, it is the first hypothesis of its kind to establish this link.CrossRefPubMedGoogle Scholar
  2. 2.
    •• Drake MJ, Kanai A, Bijos DA, Ikeda Y, Zabbarova I, Vahabi B, et al. The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity. BJU Int. 2017;119(1):22–9. This reference is a newer hypothesis which describes that chronic autonomous bladder micromotions lead to both OAB and UAB.CrossRefPubMedGoogle Scholar
  3. 3.
    Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. Standardisation sub-committee of the International Continence S: the standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61(1):37–49.CrossRefGoogle Scholar
  4. 4.
    Rigby D. Underactive bladder syndrome. Nurs Stand. 2005;19(35):57–64; quiz 66-57. Scholar
  5. 5.
    Abrams PH. Investigation of postprostatectomy problems. Urology. 1980;15(2):209–12.CrossRefGoogle Scholar
  6. 6.
    • Chapple CR, Osman NI, Birder L, van Koeveringe GA, Oelke M, Nitti VW, et al. The underactive bladder: a new clinical concept? Eur Urol. 2015;68(3):351–3. An essential publication in the management of DU. The authors define DU and provide the rationale behind this definition.CrossRefPubMedGoogle Scholar
  7. 7.
    •• Osman NI, Chapple CR, Abrams P, Dmochowski R, Haab F, Nitti V, et al. Detrusor underactivity and the underactive bladder: a new clinical entity? A review of current terminology, definitions, epidemiology, aetiology, and diagnosis. Eur Urol. 2014;65(2):389–98. The authors of this article are among the leaders of the field and have collaborated to describe the underlying pathophysiology of DU, as well as several categories of disease states which could lead to DU. The authors also describe terminology, epidemiology, and diagnosis of DU.CrossRefPubMedGoogle Scholar
  8. 8.
    Wein AJ, Kavoussi LR, Campbell MF. Campbell-Walsh urology. (editor-in-chief: AJ Wein; eds: LR Kavoussi … et al) 10th edn. Philadelphia: Elsevier Saunders; 2012.Google Scholar
  9. 9.
    Tyagi P, Smith PP, Kuchel GA, de Groat WC, Birder LA, Chermansky CJ, et al. Pathophysiology and animal modeling of underactive bladder. Int Urol Nephrol. 2014;46(Suppl 1):S11–21. Scholar
  10. 10.
    de Groat WC, Yoshimura N. Anatomy and physiology of the lower urinary tract. Handb Clin Neurol. 2015;130:61–108. Scholar
  11. 11.
    • Gormley EA, Lightner DJ, Faraday M, Vasavada SP, American Urological A, Society of Urodynamics FPM. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015;193(5):1572–80. This is a landmark article which provides guidelines for the workup and diagnosis of OAB, a collaboration between the AUA and SUFU.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoag N, Gani J. Underactive bladder: clinical features, urodynamic parameters, and treatment. Int Neurourol J. 2015;19(3):185–9. Scholar
  13. 13.
    Gammie A, Kaper M, Steup A, Yoshida S, Dorrepaal C, Kos T, Abrams P. What are the additional signs and symptoms in patients with detrusor underactivity and coexisting detrusor overactivity? Neurourol Urodyn. 2018.
  14. 14.
    Bump RC. The urethrodetrusor facilitative reflex in women: results of urethral perfusion studies. Am J Obstet Gynecol. 2000;182(4):794–802 discussion 802-794.CrossRefGoogle Scholar
  15. 15.
    Suskind AM, Smith PP. A new look at detrusor underactivity: impaired contractility versus afferent dysfunction. Curr Uro Rep. 2009;10(5):347–51.CrossRefGoogle Scholar
  16. 16.
    Smith PP. Aging and the underactive detrusor: a failure of activity or activation? Neurourol Urodyn. 2010;29(3):408–12. Scholar
  17. 17.
    Smith PP, Chalmers DJ, Feinn RS. Does defective volume sensation contribute to detrusor underactivity? Neurourol Urodyn. 2015;34(8):752–6. Scholar
  18. 18.
    Wein AJ. Re: does defective volume sensation contribute to detrusor underactivity? J Urol. 2016;196(2):499. Scholar
  19. 19.
    Steers WD, Kolbeck S, Creedon D, Tuttle JB. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest. 1991;88(5):1709–15. Scholar
  20. 20.
    Kim SW, Im YJ, Choi HC, Kang HJ, Kim JY, Kim JH. Urinary nerve growth factor correlates with the severity of urgency and pain. Int Urogynecol J. 2014;25(11):1561–7. Scholar
  21. 21.
    Suh YS, Ko KJ, Kim TH, Lee HS, Sung HH, Cho WJ, et al. Urinary nerve growth factor as a potential biomarker of treatment outcomes in overactive bladder patients. Int Neurourol J. 2017;21(4):270–81. Scholar
  22. 22.
    Vijaya G, Cartwright R, Bhide A, Derpapas A, Fernando R, Khullar V. Reliability and validity of urinary nerve growth factor measurement in women with lower urinary tract symptoms. Neurourol Urodyn. 2016;35(8):944–8. Scholar
  23. 23.
    Bultitude MI, Hills NH, Shuttleworth KE. Clinical and experimental studies on the action of prostaglandins and their synthesis inhibitors on detrusor muscle in vitro and in vivo. Br J Urol. 1976;48(7):631–7.CrossRefGoogle Scholar
  24. 24.
    Clemow DB, Steers WD, McCarty R, Tuttle JB. Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Phys. 1998;275(4 Pt 2):R1279–86.Google Scholar
  25. 25.
    Dmitrieva N, Shelton D, Rice AS, McMahon SB. The role of nerve growth factor in a model of visceral inflammation. Neuroscience. 1997;78(2):449–59.CrossRefGoogle Scholar
  26. 26.
    Maggi CA. Prostanoids as local modulators of reflex micturition. Pharmacol Res. 1992;25(1):13–20.CrossRefGoogle Scholar
  27. 27.
    Park JM, Schnermann JB, Briggs JP. Cyclooxygenase-2. A key regulator of bladder prostaglandin formation. Adv Exp Med Biol. 1999;462:171–81.CrossRefGoogle Scholar
  28. 28.
    Jiang YH, Kuo HC. Urothelial barrier deficits, suburothelial inflammation and altered sensory protein expression in detrusor underactivity. J Urol. 2017;197(1):197–203. Scholar
  29. 29.
    Brading AF. A myogenic basis for the overactive bladder. Urology. 1997;50(6A Suppl):57–67 discussion 68-73.CrossRefGoogle Scholar
  30. 30.
    Meng E, Lin WY, Lee WC, Chuang YC. Pathophysiology of overactive bladder. LUTS. 2012;4(Suppl 1):48–55. Scholar
  31. 31.
    Aizawa N, Igawa Y. Pathophysiology of the underactive bladder. Investig Clin Urol. 2017;58(Suppl 2):S82–9. Scholar
  32. 32.
    Mansfield KJ, Liu L, Mitchelson FJ, Moore KH, Millard RJ, Burcher E. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. Br J Pharmacol. 2005;144(8):1089–99. Scholar
  33. 33.
    Ito H, Aizawa N, Fujita Y, Suzuki M, Fukuhara H, Homma Y, et al. Long-term caloric restriction in rats may prevent age related impairment of in vitro bladder function. J Urol. 2015;193(6):2123–30. Scholar
  34. 34.
    Osman N, Mangera A, Hillary C, Inman R, Chapple C. The underactive bladder: detection and diagnosis. F1000Research. 2016;5.
  35. 35.
    Aldamanhori R, Osman NI, Chapple CR. Underactive bladder: pathophysiology and clinical significance. Asian J Urol. 2018;5(1):17–21. Scholar
  36. 36.
    Andersson KE, Boedtkjer DB, Forman A. The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction. Ther Adv Urol. 2017;9(1):11–27. Scholar
  37. 37.
    Ponholzer A, Temml C, Wehrberger C, Marszalek M, Madersbacher S. The association between vascular risk factors and lower urinary tract symptoms in both sexes. Eur Urol. 2006;50(3):581–6. Scholar
  38. 38.
    Pinggera GM, Mitterberger M, Steiner E, Pallwein L, Frauscher F, Aigner F, et al. Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour Doppler ultrasonography. BJU Int. 2008;102(4):470–4. Scholar
  39. 39.
    Pinggera GM, Mitterberger M, Pallwein L, Schuster A, Herwig R, Frauscher F, et al. Strasser H: alpha-blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms. BJU Int. 2008;101(3):319–24. Scholar
  40. 40.
    Brown ET, Cohn JA, Kaufman MR, Dmochowski RR, Reynolds WS. Phenotyping women with detrusor underactivity by presumed etiology: is it plausible? Neurourol Urodyn. 2017;36(4):1151–4. Scholar
  41. 41.
    Azadzoi KM, Radisavljevic ZM, Golabek T, Yalla SV, Siroky MB. Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder. J Urol. 2010;183(1):362–9. Scholar
  42. 42.
    Azadzoi KM, Radisavljevic ZM, Siroky MB. Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder. Urology. 2008;71(5):979–83. Scholar
  43. 43.
    Azadzoi KM, Tarcan T, Kozlowski R, Krane RJ, Siroky MB. Overactivity and structural changes in the chronically ischemic bladder. J Urol. 1999;162(5):1768–78.CrossRefGoogle Scholar
  44. 44.
    Azadzoi KM, Tarcan T, Siroky MB, Krane RJ. Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit. J Urol. 1999;161(5):1626–35.CrossRefGoogle Scholar
  45. 45.
    Nomiya M, Burmeister DM, Sawada N, Campeau L, Zarifpour M, Keys T, et al. Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia. J Urol. 2013;189(2):754–61. Scholar
  46. 46.
    Finkbeiner A, Lapides J. Effect of distension on blood flow in dog's urinary bladder. Investig Urol. 1974;12(3):210–2.Google Scholar
  47. 47.
    Drake MJ, Harvey IJ, Gillespie JI. Autonomous activity in the isolated Guinea pig bladder. Exp Physiol. 2003;88(1):19–30.CrossRefGoogle Scholar
  48. 48.
    Drake MJ, Hedlund P, Harvey IJ, Pandita RK, Andersson KE, Gillespie JI. Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder. J Urol. 2003;170(1):276–9. Scholar
  49. 49.
    Lagou M, Gillespie J, Kirkwood T, Harvey I, Drake MJ. Muscarinic stimulation of the mouse isolated whole bladder: physiological responses in young and ageing mice. Auton Autacoid Pharmacol. 2006;26(3):253–60. Scholar
  50. 50.
    Lentle RG, Reynolds GW, Janssen PW, Hulls CM, King QM, Chambers JP. Characterisation of the contractile dynamics of the resting ex vivo urinary bladder of the pig. BJU Int. 2015;116(6):973–83. Scholar
  51. 51.
    Parsons BA, Drake MJ, Gammie A, Fry CH, Vahabi B. The validation of a functional, isolated pig bladder model for physiological experimentation. Front Pharmacol. 2012;3:52. Scholar
  52. 52.
    Wyndaele JJ. Modulation of non-voiding activity by the muscarinergic antagonist tolterodine and the beta(3)-adrenoceptor agonist mirabegron in conscious rats with partial outflow obstruction. BJU Int. 2012;110(2 Pt 2):E143. Scholar
  53. 53.
    Brading AF, Turner WH. The unstable bladder: towards a common mechanism. Br J Urol. 1994;73(1):3–8.CrossRefGoogle Scholar
  54. 54.
    Drake MJ, Hedlund P, Mills IW, McCoy R, McMurray G, Gardner BP, et al. Structural and functional denervation of human detrusor after spinal cord injury. Lab Investig. 2000;80(10):1491–9.CrossRefGoogle Scholar
  55. 55.
    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(2):646–51.CrossRefGoogle Scholar
  56. 56.
    Sibley GN. The physiological response of the detrusor muscle to experimental bladder outflow obstruction in the pig. Br J Urol. 1987;60(4):332–6.CrossRefGoogle Scholar
  57. 57.
    Chancellor MB, Bartolone SN, DeVries EM, Diokno AC, Gibbons M, Jankowski R, et al. New technology assessment and current and upcoming therapies for underactive bladder. Neurourol Urodyn. 2018.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Henry Collier Wright
    • 1
  • Elizabeth Timbrook Brown
    • 1
    Email author
  1. 1.Department of UrologyMedstar Georgetown University HospitalWashingtonUSA

Personalised recommendations