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Pathophysiology and animal modeling of underactive bladder

  • Urology - Original Paper
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Abstract

While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.

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References

  1. Jeong SJ, Kim HJ, Lee YJ, Lee JK, Lee BK, Choo YM, Oh JJ, Lee SC, Jeong CW, Yoon CY, Hong SK, Byun SS, Lee SE (2012) Prevalence and clinical features of detrusor underactivity among elderly with lower urinary tract symptoms: a comparison between men and women. Korean J Urol 53(5):342–348. doi:10.4111/kju.2012.53.5.342

    Article  PubMed  PubMed Central  Google Scholar 

  2. Miyazato M, Yoshimura N, Chancellor MB (2013) The other bladder syndrome: underactive bladder. Rev Urol 15(1):11–22

    PubMed  PubMed Central  Google Scholar 

  3. de Groat WC (2006) Integrative control of the lower urinary tract: preclinical perspective. Br J Pharmacol 147(Suppl 2):S25–S40

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tyagi P, Thomas CA, Yoshimura N, Chancellor MB (2009) Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder. Int Braz J Urol 35(1):76–83

    Article  PubMed  Google Scholar 

  5. Tyagi P, Chancellor MB, Li Z, De Groat WC, Yoshimura N, Fraser MO, Huang L (2004) Urodynamic and immunohistochemical evaluation of intravesical capsaicin delivery using thermosensitive hydrogel and liposomes. J Urol 171(1):483–489. doi:10.1097/01.ju.0000102360.11785.d7

    Article  PubMed  CAS  Google Scholar 

  6. de Groat WC (1993) Anatomy and physiology of the lower urinary tract. Urol Clin North Am 20(3):383–401

    PubMed  Google Scholar 

  7. de Groat WC (1997) A neurologic basis for the overactive bladder. Urology 50(6A Suppl):36–52 (discussion 53–36)

    Article  PubMed  Google Scholar 

  8. de Groat WC, Araki I, Vizzard MA, Yoshiyama M, Yoshimura N, Sugaya K, Tai C, Roppolo JR (1998) Developmental and injury induced plasticity in the micturition reflex pathway. Behav Brain Res 92(2):127–140

    Article  PubMed  Google Scholar 

  9. Tyagi S, Tyagi P, Van-le S, Yoshimura N, Chancellor MB, de Miguel F (2006) Qualitative and quantitative expression profile of muscarinic receptors in human urothelium and detrusor. J Urol 176(4 Pt 1):1673–1678. doi:10.1016/j.juro.2006.06.088

    Article  PubMed  CAS  Google Scholar 

  10. de Groat WC, Fraser MO, Yoshiyama M, Smerin S, Tai C, Chancellor MB, Yoshimura N, Roppolo JR (2001) Neural control of the urethra. Scand J Urol Nephrol Suppl 207:35–43 (discussion 106–125)

    Article  PubMed  Google Scholar 

  11. Taylor JA 3rd, Kuchel GA (2006) Detrusor underactivity: clinical features and pathogenesis of an underdiagnosed geriatric condition. J Am Geriatr Soc 54(12):1920–1932. doi:10.1111/j.1532-5415.2006.00917.x

    Article  PubMed  Google Scholar 

  12. Inouye SK, Studenski S, Tinetti ME, Kuchel GA (2007) Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc 55(5):780–791. doi:10.1111/j.1532-5415.2007.01156.x

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tinetti ME, Fried TR, Boyd CM (2012) Designing health care for the most common chronic condition–multimorbidity. J Am Med Assoc 307(23):2493–2494. doi:10.1001/jama.2012.5265

    Article  CAS  Google Scholar 

  14. Yoshida M, Masunaga K, Nagata T, Satoji Y, Shiomi M (2010) The effects of chronic hyperlipidemia on bladder function in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Neurourol Urodyn 29(7):1350–1354. doi:10.1002/nau.20843

    Article  PubMed  Google Scholar 

  15. Abarbanel J, Marcus EL (2007) Impaired detrusor contractility in community-dwelling elderly presenting with lower urinary tract symptoms. Urol 69(3):436–440. doi:10.1016/j.urology.2006.11.019

    Article  PubMed  Google Scholar 

  16. Sanchez-Ortiz RF, Wang Z, Menon C, DiSanto ME, Wein AJ, Chacko S (2001) Estrogen modulates the expression of myosin heavy chain in detrusor smooth muscle. Am J Physiol Cell Physiol 280(3):C433–C440

    PubMed  CAS  Google Scholar 

  17. Zhu Q, Resnick NM, Elbadawi A, Kuchel GA (2004) Estrogen and postnatal maturation increase caveolar number and caveolin-1 protein in bladder smooth muscle cells. J Urol 171(1):467–471. doi:10.1097/01.ju.0000099480.18735.49

    Article  PubMed  CAS  Google Scholar 

  18. Zhu Q, Ritchie J, Marouf N, Dion SB, Resnick NM, Elbadawi A, Kuchel GA (2001) Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. J Urol 166(3):1136–1141

    Article  PubMed  CAS  Google Scholar 

  19. Lowalekar SK, Cristofaro V, Radisavljevic ZM, Yalla SV, Sullivan MP (2012) Loss of bladder smooth muscle caveolae in the aging bladder. Neurourol Urodyn 31(4):586–592. doi:10.1002/nau.21217

    Article  PubMed  Google Scholar 

  20. Haferkamp A, Dorsam J, Resnick NM, Yalla SV, Elbadawi A (2003) Structural basis of neurogenic bladder dysfunction. III. Intrinsic detrusor innervation. J Urol 169(2):555–562. doi:10.1097/01.ju.0000045753.02559.37

    Article  PubMed  Google Scholar 

  21. Elbadawi A, Yalla SV, Resnick NM (1993) Structural basis of geriatric voiding dysfunction. II. Aging detrusor: normal versus impaired contractility. J Urol 150(5 Pt 2):1657–1667

    PubMed  CAS  Google Scholar 

  22. Smith PP, DeAngelis A, Kuchel GA (2012) Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse. Am J Physiol Regul Integr Comp Physiol 302(5):R577–R586. doi:10.1152/ajpregu.00508.2011

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Smith PP (2010) Aging and the underactive detrusor: a failure of activity or activation? Neurourol Urodyn 29(3):408–412. doi:10.1002/nau.20765

    PubMed  Google Scholar 

  24. Azadzoi KM, Radisavljevic ZM, Siroky MB (2008) Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder. Urology 71(5):979–983. doi:10.1016/j.urology.2007.11.012

    Article  PubMed  Google Scholar 

  25. Yang Z, Dolber PC, Fraser MO (2010) Differential vulnerabilities of urethral afferents in diabetes and discovery of a novel urethra-to-urethra reflex. Am J Physiol Renal Physiol 298(1):F118–F124. doi:10.1152/ajprenal.00281.2009

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Brierly RD, Hindley RG, McLarty E, Harding DM, Thomas PJ (2003) A prospective controlled quantitative study of ultrastructural changes in the underactive detrusor. J Urol 169(4):1374–1378. doi:10.1097/01.ju.0000055781.07630.aa

    Article  PubMed  CAS  Google Scholar 

  27. Andersson KE (2010) Detrusor myocyte activity and afferent signaling. Neurourol Urodyn 29(1):97–106. doi:10.1002/nau.20784

    Article  PubMed  Google Scholar 

  28. Drake MJ, Harvey IJ, Gillespie JI, Van Duyl WA (2005) Localized contractions in the normal human bladder and in urinary urgency. BJU Int 95(7):1002–1005. doi:10.1111/j.1464-410X.2005.05455.x

    Article  PubMed  Google Scholar 

  29. Blatt AH, Brammah S, Tse V, Chan L (2012) Transurethral prostate resection in patients with hypocontractile detrusor—what is the predictive value of ultrastructural detrusor changes? J Urol 188(6):2294–2299. doi:10.1016/j.juro.2012.08.010

    Article  PubMed  Google Scholar 

  30. Griffiths DJ (2011) Use of functional imaging to monitor central control of voiding in humans. Handb Exp Pharmacol 202:81–97. doi:10.1007/978-3-642-16499-6_5

    Article  PubMed  Google Scholar 

  31. Zimmern P, Litman HJ, Nager CW, Lemack GE, Richter HE, Sirls L, Kraus SR, Sutkin G, Mueller ER (2014) Effect of aging on storage and voiding function in women with stress-predominant urinary incontinence. J Urol. doi:10.1016/j.juro.2014.01.092

    PubMed Central  Google Scholar 

  32. Lai HH, Boone TB, Thompson TC, Smith CP, Somogyi GT (2007) Using caveolin-1 knockout mouse to study impaired detrusor contractility and disrupted muscarinic activity in the aging bladder. Urology 69(2):407–411. doi:10.1016/j.urology.2006.12.018

    Article  PubMed  Google Scholar 

  33. Chai TC, Andersson KE, Tuttle JB, Steers WD (2000) Altered neural control of micturition in the aged F344 rat. Urol Res 28(5):348–354

    Article  PubMed  CAS  Google Scholar 

  34. Hotta H, Morrison JF, Sato A, Uchida S (1995) The effects of aging on the rat bladder and its innervation. Jpn J Physiol 45(5):823–836

    Article  PubMed  CAS  Google Scholar 

  35. Hotta H, Uchida S (2010) Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation. Geriatr Gerontol Int 10(Suppl 1):S127–S136. doi:10.1111/j.1447-0594.2010.00592.x

    Article  PubMed  Google Scholar 

  36. Mohammed HA, Santer RM (2002) Distribution and changes with age of calcitonin gene-related peptide- and substance P-immunoreactive nerves of the rat urinary bladder and lumbosacral sensory neurons. Eur J Morphol 40(5):293–301

    Article  PubMed  CAS  Google Scholar 

  37. Mohammed H, Hannibal J, Fahrenkrug J, Santer R (2002) Distribution and regional variation of pituitary adenylate cyclase activating polypeptide and other neuropeptides in the rat urinary bladder and ureter: effects of age. Urol Res 30(4):248–255. doi:10.1007/s00240-002-0261-6

    Article  PubMed  CAS  Google Scholar 

  38. Lluel P, Deplanne V, Heudes D, Bruneval P, Palea S (2003) Age-related changes in urethrovesical coordination in male rats: relationship with bladder instability? Am J Physiol Regul Integr Comp Physiol 284(5):R1287–R1295. doi:10.1152/ajpregu.00499.2001

    PubMed  CAS  Google Scholar 

  39. Lluel P, Palea S, Barras M, Grandadam F, Heudes D, Bruneval P, Corman B, Martin DJ (2000) Functional and morphological modifications of the urinary bladder in aging female rats. Am J Physiol Regul Integr Comp Physiol 278(4):R964–R972

    PubMed  CAS  Google Scholar 

  40. Lluel P, Palea S, Ribiere P, Barras M, Teillet L, Corman B (2003) Increased adrenergic contractility and decreased mRNA expression of NOS III in aging rat urinary bladders. Fundam Clin Pharmacol 17(5):633–641

    Article  PubMed  CAS  Google Scholar 

  41. Iaina A, Serban I, Kapuler S, Gavendo S, Lindner A, Eliahou HE (1988) Beta-adrenergic receptors in the urinary bladder of adult and developing rats. Isr J Med Sci 24(4–5):237–240

    PubMed  CAS  Google Scholar 

  42. Goins WF, Yoshimura N, Phelan MW, Yokoyama T, Fraser MO, Ozawa H, Bennett NJ, de Groat WC, Glorioso JC, Chancellor MB (2001) Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction. J Urol 165(5):1748–1754

    Article  PubMed  CAS  Google Scholar 

  43. Gray MA, Wang CC, Sacks MS, Yoshimura N, Chancellor MB, Nagatomi J (2008) Time-dependent alterations of select genes in streptozotocin-induced diabetic rat bladder. Urology 71(6):1214–1219. doi:10.1016/j.urology.2007.11.054

    Article  PubMed  Google Scholar 

  44. Sasaki K, Chancellor MB, Goins WF, Phelan MW, Glorioso JC, de Groat WC, Yoshimura N (2004) Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes 53(10):2723–2730

    Article  PubMed  CAS  Google Scholar 

  45. Sasaki K, Chancellor MB, Phelan MW, Yokoyama T, Fraser MO, Seki S, Kubo K, Kumon H, Groat WC, Yoshimura N (2002) Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia. J Urol 168(3):1259–1264. doi:10.1097/01.ju.0000023400.17372.3e

    Article  PubMed  Google Scholar 

  46. Sasaki K, Yoshimura N, Chancellor MB (2003) Implications of diabetes mellitus in urology. Urol Clin North Am 30(1):1–12

    Article  PubMed  Google Scholar 

  47. Dong XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, White MF (2008) Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab 8(1):65–76. doi:10.1016/j.cmet.2008.06.006

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  48. Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT, Depinho RA, Puigserver P, White MF (2009) Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med 15(11):1307–1311. doi:10.1038/nm.2049

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Wang Z, Cheng Z, Cristofaro V, Li J, Xiao X, Gomez P, Ge R, Gong E, Strle K, Sullivan MP, Adam RM, White MF, Olumi AF (2012) Inhibition of TNF-alpha improves the bladder dysfunction that is associated with type 2 diabetes. Diabetes 61(8):2134–2145. doi:10.2337/db11-1763

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Torimoto K, Fraser MO, Hirao Y, De Groat WC, Chancellor MB, Yoshimura N (2004) Urethral dysfunction in diabetic rats. J Urol 171(5):1959–1964. doi:10.1097/01.ju.0000121283.92963.05

    Article  PubMed  Google Scholar 

  51. Torimoto K, Hirao Y, Matsuyoshi H, de Groat WC, Chancellor MB, Yoshimura N (2005) alpha1-Adrenergic mechanism in diabetic urethral dysfunction in rats. J Urol 173(3):1027–1032. doi:10.1097/01.ju.0000146268.45662.36

    Article  PubMed  CAS  Google Scholar 

  52. Christ GJ, Bushman W, Fraser MO (2009) Impact of diabetes and obesity on the prostate and urethra: implications to improved bladder dysfunction understanding and treatment. J Urol 182(6 Suppl):S38–S44. doi:10.1016/j.juro.2009.07.085

    Article  PubMed  Google Scholar 

  53. Li Y, Sun Y, Zhang Z, Feng X, Meng H, Li S, Zhu Y, Chen S, Wang Y, Wang J, Zhang D, Jiang X, Li N, Shi B (2013) Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model. BJU Int 112(2):E143–E150. doi:10.1111/bju.12172

    Article  PubMed  CAS  Google Scholar 

  54. Bschleipfer T, Nandigama R, Moeller S, Illig C, Weidner W, Kummer W (2012) Bladder outlet obstruction influences mRNA expression of cholinergic receptors on sensory neurons in mice. Life Sci 91(21–22):1077–1081. doi:10.1016/j.lfs.2012.05.007

    Article  PubMed  CAS  Google Scholar 

  55. Philyppov IB, Paduraru ON, Andreev YA, Grishin EV, Shuba YM (2012) Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth muscle by analgesic toxins from sea anemone Heteractis crispa. Life Sci 91(19–20):912–920. doi:10.1016/j.lfs.2012.09.001

    Article  PubMed  CAS  Google Scholar 

  56. Fu LW, Longhurst JC (1998) Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats. J Physiol 509(Pt 3):729–740

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  57. Yoshida M, Masunaga K, Nagata T, Satoji Y, Shiomi M (2010) The effects of chronic hyperlipidemia on bladder function in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Neurourol Urodyn 29(7):1350–1354. doi:10.1002/nau.20843

    Article  PubMed  Google Scholar 

  58. MacDonald SW, Karlsson S, Rieckmann A, Nyberg L, Backman L (2012) Aging-related increases in behavioral variability: relations to losses of dopamine D1 receptors. J Neurosci 32(24):8186–8191. doi:10.1523/JNEUROSCI.5474-11.2012

    Article  PubMed  CAS  Google Scholar 

  59. Kobayashi S, Muroyama A, Matsushima H, Yoshimura I, Mitsumoto Y (2012) Oral administration of coenzyme Q(1)(0) reduces MPTP-induced loss of dopaminergic nerve terminals in the striatum in mice. Neurol Sci 33(1):195–199. doi:10.1007/s10072-011-0627-z

    Article  PubMed  Google Scholar 

  60. Yoshimura N, Mizuta E, Kuno S, Sasa M, Yoshida O (1993) The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuropharmacology 32(4):315–321

    Article  PubMed  CAS  Google Scholar 

  61. Sekido N, Jyoraku A, Okada H, Wakamatsu D, Matsuya H, Nishiyama H (2012) A novel animal model of underactive bladder: analysis of lower urinary tract function in a rat lumbar canal stenosis model. Neurourol Urodyn 31(7):1190–1196. doi:10.1002/nau.21255

    Article  PubMed  Google Scholar 

  62. Chang HH, Havton LA (2013) Serotonergic 5-HT(1A) receptor agonist (8-OH-DPAT) ameliorates impaired micturition reflexes in a chronic ventral root avulsion model of incomplete cauda equina/conus medullaris injury. Exp Neurol 239:210–217. doi:10.1016/j.expneurol.2012.10.015

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  63. Schnegelsberg B, Sun TT, Cain G, Bhattacharya A, Nunn PA, Ford AP, Vizzard MA, Cockayne DA (2010) Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function. Am J Physiol Regul Integr Comp Physiol 298(3):R534–R547. doi:10.1152/ajpregu.00367.2009

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  64. Smith PP, Kuchel GA (2010) Continuous uroflow cystometry in the urethane-anesthetized mouse. Neurourol Urodyn 29(7):1344–1349. doi:10.1002/nau.20850

    Article  PubMed  PubMed Central  Google Scholar 

  65. Rahnama’i MS, Biallosterski BT, de Wachter SG, Van Kerrebroeck PE, van Koeveringe GA (2012) The distribution of the prostaglandin E receptor type 2 (EP2) in the detrusor of the guinea pig. Prostaglandins Other Lipid Mediat 99(3–4):107–115. doi:10.1016/j.prostaglandins.2012.08.005

    Article  PubMed  Google Scholar 

  66. Rahnama’i MS, de Wachter SG, van Koeveringe GA, van Kerrebroeck PE, de Vente J, Gillespie JI (2011) The relationship between prostaglandin E receptor 1 and cyclooxygenase I expression in guinea pig bladder interstitial cells: proposition of a signal propagation system. J Urol 185(1):315–322. doi:10.1016/j.juro.2010.09.005

    Article  PubMed  Google Scholar 

  67. Rahnama’i MS, van Kerrebroeck PE, de Wachter SG, van Koeveringe GA (2012) The role of prostanoids in urinary bladder physiology. Nat Rev Urol 9(5):283–290. doi:10.1038/nrurol.2012.33

    Article  PubMed  Google Scholar 

  68. Rahnama’i MS, van Koeveringe GA, Essers PB, de Wachter SG, de Vente J, van Kerrebroeck PE, Gillespie JI (2010) Prostaglandin receptor EP1 and EP2 site in guinea pig bladder urothelium and lamina propria. J Urol 183(3):1241–1247. doi:10.1016/j.juro.2009.11.004

    Article  PubMed  Google Scholar 

  69. Kim JC, Park EY, Hong SH, Seo SI, Park YH, Hwang TK (2005) Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol 12(10):875–880. doi:10.1111/j.1442-2042.2005.01140.x

    Article  PubMed  CAS  Google Scholar 

  70. McCafferty GP, Misajet BA, Laping NJ, Edwards RM, Thorneloe KS (2008) Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice. Am J Physiol Renal Physiol 295(2):F507–F514. doi:10.1152/ajprenal.00054.2008

    Article  PubMed  CAS  Google Scholar 

  71. Tanaka I, Nagase K, Tanase K, Aoki Y, Akino H, Yokoyama O (2011) Modulation of stretch evoked adenosine triphosphate release from bladder epithelium by prostaglandin E(2). J Urol 185(1):341–346. doi:10.1016/j.juro.2010.09.042

    Article  PubMed  CAS  Google Scholar 

  72. Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P (2005) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174(3):977–982; discussion 982–973. doi:10.1097/01.ju.0000169481.42259.54

  73. Cockayne DA, Dunn PM, Zhong Y, Rong W, Hamilton SG, Knight GE, Ruan HZ, Ma B, Yip P, Nunn P, McMahon SB, Burnstock G, Ford AP (2005) P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol 567(Pt 2):621–639. doi:10.1113/jphysiol.2005.088435

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  74. Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 21(15):5670–5677

    PubMed  CAS  Google Scholar 

  75. Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407(6807):1011–1015. doi:10.1038/35039519

    Article  PubMed  CAS  Google Scholar 

  76. Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A (2004) Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63(3 Suppl 1):17–23. doi:10.1016/j.urology.2003.11.003

    Article  PubMed  Google Scholar 

  77. Brierly RD, Hindley RG, McLarty E, Harding DM, Thomas PJ (2003) A prospective evaluation of detrusor ultrastructural changes in bladder outlet obstruction. BJU Int 91(4):360–364

    Article  PubMed  CAS  Google Scholar 

  78. Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2011) Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals. Age (Dordr) 33(1):81–88. doi:10.1007/s11357-010-9163-7

    Article  CAS  Google Scholar 

  79. Murakami S, Yoshida M, Masunaga K, Maeda Y, Ueda S (2008) Change in acetylcholine release from rat bladder with partial outlet obstruction. BJU Int 101(5):633–639. doi:10.1111/j.1464-410X.2007.07325.x

    Article  PubMed  CAS  Google Scholar 

  80. McMurray G, Casey JH, Naylor AM (2006) Animal models in urological disease and sexual dysfunction. Br J Pharmacol 147(Suppl 2):S62–S79. doi:10.1038/sj.bjp.0706630

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  81. Gabella G (1999) Structure of the intramural nerves of the rat bladder. J Neurocytol 28(8):615–637

    Article  PubMed  CAS  Google Scholar 

  82. Gabella G, Davis C (1998) Distribution of afferent axons in the bladder of rats. J Neurocytol 27(3):141–155

    Article  PubMed  CAS  Google Scholar 

  83. Chang SJ, Chiang IN, Yu HJ (2008) The effectiveness of tamsulosin in treating women with voiding difficulty. Int J Urol 15(11):981–985. doi:10.1111/j.1442-2042.2008.02134.x

    Article  PubMed  CAS  Google Scholar 

  84. Insel TR (2007) From animal models to model animals. Biol Psychiatry 62(12):1337–1339. doi:10.1016/j.biopsych.2007.10.001

    Article  PubMed  Google Scholar 

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Acknowledgments

Funding for this conference was made possible (in part) by 1R13AG047010 from the National Institute on Aging. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the NIH; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

Conflict of interest

Vincent Tse has conflicts of interest related to Allergan, Astellas, and American Medical Systems. Michael B Chancellor has conflicts of interest related to Allergan, Astellas, Cook, Lipella, Medtronic, Pfizer, Targacept. There are no conflicts of interest for Pradeep Tyagi, William C. de Groat, Lori A. Birder, Christopher J. Chermansky, Rosalyn M. Adam, George A. Kuchel, Philip P. Smith and Naoki Yoshimura.

Author information

Authors and Affiliations

  1. Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA

    Pradeep Tyagi, Christopher J. Chermansky & Naoki Yoshimura

  2. Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA

    William C. de Groat

  3. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Lori A. Birder

  4. Department of Surgery, University of Connecticut Health Center, Farmington, CT, USA

    Phillip P. Smith

  5. UConn Center on Aging, University of Connecticut Health Center, Farmington, CT, USA

    Phillip P. Smith & George A. Kuchel

  6. Department of Urology, Boston Children’s Hospital, Boston, MA, USA

    Rosalyn M. Adam

  7. Department of Surgery, Harvard Medical School, Boston, MA, USA

    Rosalyn M. Adam

  8. Department of Urology, Concord Hospital, University of Sydney, Concord, NSW, Australia

    Vincent Tse

  9. Department of Urology, Beaumont Hospital, Royal Oak, MI, USA

    Michael B. Chancellor

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  1. Pradeep Tyagi
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  7. Rosalyn M. Adam
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Correspondence to Michael B. Chancellor.

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Tyagi, P., Smith, P.P., Kuchel, G.A. et al. Pathophysiology and animal modeling of underactive bladder. Int Urol Nephrol 46 (Suppl 1), 11–21 (2014). https://doi.org/10.1007/s11255-014-0808-9

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  • DOI: https://doi.org/10.1007/s11255-014-0808-9

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