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Mechanisms of Disease: central nervous system involvement in overactive bladder syndrome

Abstract

The pathophysiology of overactive bladder syndrome (OABS) and detrusor overactivity (DO) is complex and involves both peripheral and central nervous system (CNS) factors. Central in OABS is urgency, the pathophysiology of which is unknown. Increased afferent activity, decreased capacity to process afferent information, decreased suprapontine inhibition, and increased sensitivity to contraction-mediating transmitters are all potential causes of DO and OABS. Because both urgency and initiation of the micturition reflex depend on afferent input from the lower urinary tract, it seems logical that in the search for new therapies for DO/OABS, afferent functions and central control of afferent functions are targets of interest. Voiding and storage reflexes involve several transmitters and transmitter systems that could be targets for the development of drugs that control DO/OABS. Perturbations of these systems are found in CNS disorders associated with DO/OAB, such as stroke, Parkinson's disease, spinal cord injury and multiple sclerosis. This short overview focuses on the afferent pathways and on how the transmitter systems that control micturition can be perturbed by disease to give rise to DO/OABS.

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Figure 1
Figure 2: Different mechanisms can initiate the micturition reflex.
Figure 3: Spinal cord injury can evoke activity in silent C-fibers, initiating a spinal voiding reflex.

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References

  1. Abrams P et al. (2002) The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 21: 167–178

    Article  Google Scholar 

  2. de Groat WC et al. (1993) Neurophysiology of micturition and its modification in animal models of human disease. In Nervous Control of the Urogenital System 227–289 (Ed. Maggi CA) London: Harwood Academic Publishers

    Google Scholar 

  3. Klein LA (1988) Urge incontinence can be a disease of bladder sensors. J Urol 139: 1010–1014

    Article  CAS  Google Scholar 

  4. Morrison J et al. (2002) Neurophysiology and neuropharmacology. In Incontinence, 2nd International Consultation on Incontinence 85–161 (Eds Abrams P et al.) Plymouth: Plymbridge Distributors Ltd

    Google Scholar 

  5. Steers WD (2002) Overactive bladder (OAB): what we thought we knew and what we know today. Eur Urol (Suppl 1): 3–10

  6. Lincoln J and Burnstock G (1993) Autonomic innervation of the urinary bladder and urethra. In Nervous Control of the Urogenital System 33–68 (Ed Maggi CA) London: Harwood Academic Publishers

  7. Wyndaele JJ (1998) The normal pattern of perception of bladder filling during cystometry studied in 38 young healthy volunteers. J Urol 160: 479–481

    Article  CAS  Google Scholar 

  8. Morrison JFB (1987) Sensations arising from the lower urinary tract. In The Physiology of the Lower Urinary Tract 89–131 (Eds Torrens M and Morrison JFB) Berlin: Springer-Verlag

    Chapter  Google Scholar 

  9. Oliver S et al. (2003) Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulation. Neurourol Urodyn 22: 7–16

    Article  Google Scholar 

  10. Cucchi A et al. (2003) Voiding urgency and detrusor contractility in women with overactive bladders. Neurourol Urodyn 22: 223–226

    Article  CAS  Google Scholar 

  11. Andersson KE (2002) Bladder activation: afferent mechanisms. Urology 59 (Suppl 1): 43–50

    Article  Google Scholar 

  12. de Groat WC et al. (1999) Basic neurophysiology and neuropharmacology. In Incontinence, 1st International Consultation on Incontinence 105–154 (Eds Abrams P et al.) Plymouth: Plymbridge Distributors Ltd

    Google Scholar 

  13. Taniguchi N et al. (2002) A study of micturition inducing sites in the periaqueductal gray of the mesencephalon. J Urol 168: 1626–1631

    Article  Google Scholar 

  14. Griffiths D et al. (1990) Control and coordination of bladder and urethral function in the brainstem of the cat. Neurourol Urodyn 9: 63–82

    Article  Google Scholar 

  15. Blok BF and Holstege G (1999) Two pontine micturition centers in the cat are not interconnected directly: implications for the central organization of micturition. J Comp Neurol 403: 209–218

    Article  CAS  Google Scholar 

  16. Nour S et al. (2000) Cerebral activation during micturition in normal men. Brain 123: 781–789

    Article  Google Scholar 

  17. Athwal BS et al. (2001) Brain responses to changes in bladder volume and urge to void in healthy men. Brain 124: 369–377

    Article  CAS  Google Scholar 

  18. Matsuura S et al. (2002) Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study. J Urol 168: 2035–2039

    Article  Google Scholar 

  19. Sakakibara R et al. (1996) Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 137: 47–56

    Article  CAS  Google Scholar 

  20. Downie JW (1999) Pharmacological manipulation of central micturition circuitry. Curr Opin CPNS Invest Drugs 1: 231–239

    CAS  Google Scholar 

  21. de Groat WC and Yoshimura N (2001) Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol 41: 691–721

    Article  CAS  Google Scholar 

  22. Andersson KE (2004) New pharmacologic targets for the treatment of the overactive bladder: an update. Urology 63 (Suppl 1): 32–41

    Article  Google Scholar 

  23. Belayev L et al. (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27: 1616–1622

    Article  CAS  Google Scholar 

  24. Yokoyama O et al. (1997) Influence of anesthesia on bladder hyperactivity induced by middle cerebral artery occlusion in the rat. Am J Physiol 273: R1900–R1907

    Article  CAS  Google Scholar 

  25. Kaidoh K et al. (2002) Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats. J Urol 168: 1247–1252

    Article  CAS  Google Scholar 

  26. Yokoyama O et al. (2000) Role of the forebrain in bladder overactivity following cerebral infarction in the rat. Exp Neurol 163: 469–476

    Article  CAS  Google Scholar 

  27. Yokoyama O et al. (1999) Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion. Am J Physiol 276: R935–R942

    CAS  PubMed  Google Scholar 

  28. Yokoyama O et al. (2002) Changes in dopaminergic and glutamatergic excitatory mechanisms of micturition reflex after middle cerebral artery occlusion in conscious rats. Exp Neurol 173: 129–135

    Article  CAS  Google Scholar 

  29. Kodama K et al. (2002) Contribution of cerebral nitric oxide to bladder overactivity after cerebral infarction in rats. J Urol 167: 391–396

    Article  CAS  Google Scholar 

  30. Kanie S et al. (2000) GABAergic contribution to rat bladder hyperactivity after middle cerebral artery occlusion. Am J Physiol Regul Integr Comp Physiol 279: R1230–R1238

    Article  CAS  Google Scholar 

  31. Fowler CJ (2001) Urinary disorders in Parkinson's disease and multiple system atrophy. Funct Neurol 16: 277–282

    CAS  PubMed  Google Scholar 

  32. Shefchyk SJ (2002) Spinal cord neural organization controlling the urinary bladder and striated sphincter. Prog Brain Res 137: 71–82

    Article  Google Scholar 

  33. Singer C (1998) Urinary dysfunction in Parkinson's disease. Clin Neurosci 5: 78–86

    Article  CAS  Google Scholar 

  34. Berger Y et al. (1987) Urodynamic findings in Parkinson's disease. J Urol 138: 836–838

    Article  CAS  Google Scholar 

  35. Fowler CJ (1999) Neurological disorders of micturition and their treatment. Brain 122: 1213–1231

    Article  Google Scholar 

  36. Kontani H et al. (1990) Dopamine receptor subtypes that induce hyperactive urinary bladder response in anesthetized rats. Jpn J Pharmacol 54: 482–486

    Article  CAS  Google Scholar 

  37. Seki S et al. (2001) Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats. Neurourol Urodyn 20: 105–113

    Article  CAS  Google Scholar 

  38. Gerfen CR (2000) Molecular effects of dopamine on striatal-projection pathways. Trends Neurosci 23: S64–S70

    Article  CAS  Google Scholar 

  39. Pavlakis AJ et al. (1983) Neurourologic findings in Parkinson's disease. J Urol 129: 80–83

    Article  CAS  Google Scholar 

  40. Sakakibara R et al. (2001) SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction. J Neurol Sci 187: 55–59

    Article  CAS  Google Scholar 

  41. Yoshimura N et al. (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: 315–321

    Article  CAS  Google Scholar 

  42. Litwiller SE et al. (1999) Multiple sclerosis and the urologist. J Urol 161: 743–757

    Article  CAS  Google Scholar 

  43. Fernandez O (2002) Mechanisms and current treatments of urogenital dysfunction in multiple sclerosis. J Neurol 249: 1–8

    Article  Google Scholar 

  44. Sirls LT et al. (1994) Role of limited evaluation and aggressive medical management in multiple sclerosis: a review of 113 patients. J Urol 151: 946–950

    Article  CAS  Google Scholar 

  45. Mizusawa H et al. (2000) A rat model for investigation of bladder dysfunction associated with demyelinating disease resembling multiple sclerosis. Neurourol Urodyn 19: 689–699

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Support was obtained from the Swedish Research Council (grant no. 6865) and the Medical Faculty, University of Lund.

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Correspondence to Karl-Erik Andersson.

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Andersson, KE. Mechanisms of Disease: central nervous system involvement in overactive bladder syndrome. Nat Rev Urol 1, 103–108 (2004). https://doi.org/10.1038/ncpuro0021

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