Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The bladder–brain connection: putative role of corticotropin-releasing factor

Nature Reviews Urology volume 8, pages 19–28 (2011)Cite this article

Subjects

Abstract

The coordination of pelvic visceral activity with appropriate elimination behaviors is a complex task that requires reciprocal communication between the brain and pelvic organs. Barrington's nucleus, located in the pons, is central to a circuit involved in this function. Barrington's nucleus neurons project to both pelvic visceral motorneurons and cerebral norepinephrine neurons that modulate behavior. This circuit coordinates the descending limb of the micturition reflex with a central limb that initiates arousal and shifts the focus of attention to facilitate elimination behavior. The same circuitry that links the bladder and brain enables pathological processes in one target of the circuit to be expressed in the other. Urological disorders can, therefore, have cognitive and behavioral consequences by affecting components of this circuit; and in the opposing direction, psychosocial stressors can produce voiding dysfunctions and bladder pathology. The stress-related neuropeptide, corticotropin-releasing factor, which is prominent in Barrington's nucleus neurons, is a potential mediator of these effects.

Key Points

  • Barrington's nucleus in the pons coordinates the descending visceral limb of the micturition reflex with a central limb that initiates arousal and facilitates elimination behavior

  • The stress-related neurotransmitter, corticotropin-releasing factor, regulates both limbs of the micturition reflex owing to its actions in the central and spinal projections of Barrington's nucleus neurons

  • Pelvic visceral disorders can affect the major brain norepinephrine nucleus, the locus coeruleus and have neurobehavioral consequences

  • Psychosocial stressors can produce voiding dysfunctions and bladder pathology via spinal projections of Barrington's nucleus neurons

  • Neural circuits linking the brain and bladder provide a basis for the coexistence of bladder and neurobehavioral symptoms

  • Pharmacological modulation of neurotransmitters expressed by Barrington's nucleus neurons—such as corticotropin-releasing factor—offers a novel approach for the treatment of bladder disorders

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Fluorescent photomicrograph of a rat brain section at the level of Barrington's nucleus.
Figure 2: Schematic diagram of the circuitry centered around BN that links the brain and pelvic viscera.
Figure 3: Corticotropin-releasing factor (CRF) is a major neurotransmitter in Barrington's nucleus neurons.
Figure 4: Simultaneous EEG and cystometry recordings obtained from a sham-treated rat and two PBOO rats.
Figure 5: The heat maps indicate time-averaged bladder pressure and corresponding EEG generated over 4–5 micturition cycles from the same rats as in Figure 4.
Figure 6: Social stress alters bladder urodynamics.

Similar content being viewed by others

References

  1. Longstreth, G. F. Irritable bowel syndrome and chronic pelvic pain. Obstet. Gynecol. Surv. 49, 505–507 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Lydiard, R. B., Fossey, M. D., Marsh, W. & Ballenger, J. C. Prevalence of psychiatric disorders in patients with irritable bowel syndrome. Psychosomatics 34, 229–234 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. Lydiard, R. B. et al. Panic disorder and gastrointestinal symptoms: findings from the NIMH epidemiologic catchment area project. Am. J. Psych. 151, 64–70 (1994).

    Article  CAS  Google Scholar 

  4. Whorwell, P. J., Lupton, E. W., Erduran, D. & Wilson, K. Bladder smooth muscle dysfunction in patients with irritable bowel syndrome. Gut 27, 1014–1017 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Whorwell, P. J., McCallum, M., Creed, F. H. & Roberts, C. T. Non-colonic features of irritable bowel syndrome. Gut 27, 37–40 (1987).

    Article  Google Scholar 

  6. Perry, S., McGrother, C. W. & Turner, K. An investigation of the relationship between anxiety and depression and urge incontinence in women: development of a psychological model. Br. J. Health Psychol. 11, 463–482 (2006).

    Article  PubMed  Google Scholar 

  7. Von Gontard, A. & Hollmann, E. Comorbidity of functional urinary incontinence and encopresis: somatic and behavioral associations. J. Urol. 171, 2644–2647 (2004).

    Article  PubMed  Google Scholar 

  8. Baeyens, D. et al. Attention deficit/hyperactivity disorder in children with nocturnal enuresis. J. Urol. 171, 2576–2579 (2004).

    Article  PubMed  Google Scholar 

  9. Desjardins, C., Maruniak, J. A. & Bronson, F. H. Social rank in house mice: differentiation revealed by ultraviolet visualization of urinary marking patterns. Science 182, 939–941 (1973).

    Article  CAS  PubMed  Google Scholar 

  10. Valentino, R. J., Chen, S., Zhu, Y. & Aston-Jones, G. Evidence for divergent projections of corticotropin-releasing hormone neurons of Barrington's nucleus to the locus coeruleus and spinal cord. Brain Res. 732, 1–15 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Aston-Jones, G., Shipley, M. T. & Grzanna, R. in The Rat Brain (ed. Paxinos, G.) 183–213 (Academic Press, London, 1995).

    Google Scholar 

  12. Swanson, L. W. & Hartman, B. K. The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat using dopamine-beta-hydroxylase as a marker. J. Comp. Neurol. 163, 467–506 (1976).

    Article  Google Scholar 

  13. Aston-Jones, G. & Cohen, J. D. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu. Rev. Neurosci. 28, 403–450 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Berridge, C. W. & Waterhouse, B. D. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res. Brain Res. Rev. 42, 33–84 (2003).

    Article  PubMed  Google Scholar 

  15. Valentino, R. J., Pavcovich, L. A. & Hirata, H. Evidence for corticotropin-releasing hormone projections from Barrington's nucleus to the periaqueductal gray region and dorsal motor nucleus of the vagus in the rat. J. Comp. Neurol. 363, 402–422 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Sakanaka, M., Shibasaki, T. & Lederes, K. Corticotropin-releasing factor-like immunoreactivity in the rat brain as revealed by a modified cobalt-glucose oxide-diaminobenzidene method. J. Comp. Neurol. 260, 256–298 (1987).

    Article  CAS  PubMed  Google Scholar 

  17. Vincent, S. R. & Satoh, K. Corticotropin-releasing factor (CRF) immunoreactivity in the dorsolateral pontine tegmentum: further studies on the micturition reflex system. Brain Res. 308, 387–391 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Vale, W., Spiess, J., Rivier, C. & Rivier, J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213, 1394–1397 (1981).

    Article  CAS  PubMed  Google Scholar 

  19. Owens, M. J. & Nemeroff, C. B. Physiology and pharmacology of corticotropin-releasing factor. Pharmacol. Rev. 43, 425–474 (1991).

    CAS  PubMed  Google Scholar 

  20. Valentino, R. J., Miselis, R. R. & Pavcovich, L. A. Pontine regulation of pelvic viscera: Pharmacological target for pelvic visceral dysfunctions. Trends Pharmacol. Sci. 20, 253–266 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Noto, H., Roppolo, J. R., Steers, W. D. & De Groat, W. C. Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat. Brain Res. 492, 99–115 (1989).

    Article  CAS  PubMed  Google Scholar 

  22. Pavcovich, L. A. & Valentino, R. J. Central regulation of micturition in the rat by corticotropin-releasing hormone from Barrington's nucleus. Neurosci. Lett. 196, 185–188 (1995).

    Article  CAS  PubMed  Google Scholar 

  23. Willette, R. N., Morrison, S., Sapru, H. N. & Reis, D. J. Stimulation of opiate receptors in the dorsal pontine tegmentum inhibits reflex contraction of the urinary bladder. J. Pharmacol. Exp. Ther. 244, 403–409 (1988).

    CAS  PubMed  Google Scholar 

  24. Barrington, F. J. T. The effect of lesion of the hind- and mid-brain on micturition in the cat. Quart. J. Exp. Physiol. 15, 81–102 (1925).

    Article  Google Scholar 

  25. Hida, T. & Shimazu, N. The interrelation between the laterdorsal tegmental area and lumbosacral segments of rats as studied by HRP method. Arch. Histol. Jap. 45, 495–504 (1982).

    Article  CAS  PubMed  Google Scholar 

  26. Loewy, A. D., Saper, C. B. & Baker, R. P. Descending projections from the pontine micturition center. Brain Res. 172, 533–538 (1979).

    Article  CAS  PubMed  Google Scholar 

  27. Blok, B. F. M. & Holstege, G. Ultrastructural evidence for a direct pathway from the pontine micturition center to parasympathetic preganglionic motoneurons of the bladder of the cat. Neurosci. Lett. 222, 195–198 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Rouzade-Dominguez, M. L., Pernar, L., Beck, S. & Valentino, R. J. Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli: a juxtacellular labeling study. Eur. J. Neurosci. 18, 3325–3334 (2003).

    Article  PubMed  Google Scholar 

  29. Ding, Y. Q. et al. Direct projections from lumbosacral spinal cord to Barrington's nucleus in the rat: a special reference to micturition reflex. J. Comp. Neurol. 389, 149–160 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Blok, B. F. M., De Weerd, H. & Holstege, G. Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition center or M-region in the cat: a new concept for the organization of the micturition reflex with the periaqueductal gray as a central relay. J. Comp. Neurol. 359, 300–309 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Rouzade-Dominguez, M. L., Miselis, R. & Valentino, R. J. Central representation of bladder and colon revealed by dual transsynaptic tracing: substrates for pelvic visceral coordination. Eur. J. Neurosci. 18, 3311–3324 (2003).

    Article  PubMed  Google Scholar 

  32. Marson, L. Central nervous system neurons identified after injection of pseudorabies virus into the rat clitoris. Neurosci. Lett. 190, 41–44 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Marson, L. & McKenna, K. E. CNS cell groups involved in the control of the ischiocavernosus and bulbospongiosus muscles; a transneuronal tracing study using pseudorabies virus. J. Comp. Neurol. 374, 161–179 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Vizzard, M. A., Brisson, M. & de Groat, W. C. Transneuronal labeling of neurons in the adult rat central nervous system following inoculation of pseudorabies virus into the colon. Cell Tissue Res. 299, 9–26 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. Lambert, S. M. & Zderic, S. A. in Textbook of Female Urology and Urogynecology (eds Cardozo, L. & Staskin, D.) 172–184 (Informa Healthcare, UK, 2010).

    Book  Google Scholar 

  36. Guo, Y. J. et al. Lower urinary tract symptoms in women with irritable bowel syndrome. Int. J. Urol. 17, 175–181 (2010).

    Article  PubMed  Google Scholar 

  37. Grzanna, R. & Molliver, M. E. The locus coeruleus in the rat: an immunohistochemical delineation. Neuroscience 5, 21–40 (1980).

    Article  CAS  PubMed  Google Scholar 

  38. Bouret, S. & Sara, S. J. Network reset: a simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci. 28, 574–582 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Aston-Jones, G. & Bloom, F. E. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J. Neurosci. 1, 887–900 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Elam, M., Thoren, T. & Svensson, T. H. Locus coeruleus neurons and sympathetic nerves: activation by visceral afferents. Brain Res. 375, 117–125 (1986).

    Article  CAS  PubMed  Google Scholar 

  41. Foote, S. L., Aston-Jones, G. & Bloom, F. E. Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc. Natl Acad. Sci. USA 77, 3033–3037 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lechner, S., Curtis, A., Brons, R. & Valentino, R. Locus coeruleus activation by colon distention: role of corticotropin-releasing factor and excitatory amino acids. Brain Res. 756, 114–124 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Page, M. E., Akaoka, H., Aston-Jones, G. & Valentino, R. J. Bladder distention activates locus coeruleus neurons by an excitatory amino acid mechanism. Neuroscience 51, 555–563 (1992).

    Article  CAS  PubMed  Google Scholar 

  44. Bale, T. L. & Vale, W. W. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu. Rev. Pharmacol. Toxicol. 44, 525–557 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Valentino, R. J. & Van Bockstaele, E. Convergent regulation of locus coeruleus activity as an adaptive response to stress. Eur. J. Pharmacol. 583, 194–203 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Van Bockstaele, E. J., Colago, E. E. O. & Valentino, R. J. Corticotropin-releasing factor-containing axon terminals synapse onto catecholamine dendrites and may presynaptically modulate other afferents in the rostral pole of the nucleus locus coeruleus in the rat brain. J. Comp. Neurol. 364, 523–534 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Page, M. E., Berridge, C. W., Foote, S. L. & Valentino, R. J. Corticotropin-releasing factor in the locus coeruleus mediates EEG activation associated with hypotensive stress. Neurosci. Lett. 164, 81–84 (1993).

    Article  CAS  PubMed  Google Scholar 

  48. Curtis, A. L., Bello, N. T., Connally, K. R. & Valentino, R. J. Corticotropin-releasing factor neurons of the central nucleus of the amygdala mediate locus coeruleus activation by cardiovascular stress. J. Neuroendocrinol. 14, 667–682 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Valentino, R. J., Kosboth, M., Winogren, M. L. & Miselis, R. R. Transneuronal labeling from the rat distal colon: anatomical evidence for regulation of distal colon function by a pontine corticotropin-releasing factor system. J. Comp. Neurol. 417, 399–414 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. Lovejoy, D. A. & Balment, R. J. Evolution and physiology of the corticotropin-releasing factor (CRF) family of neuropeptides in vertebrates. Gen. Comp. Endocrinol. 115, 1–22 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Denver, R. Structural and functional evolution of vertebrate neuroendocrine stress systems. Ann. NY Acad. Sci. 1163, 1–16 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Ruggiero, D. A., Underwood, M. D., Rice, P. M., Mann, J. J. & Arango, V. Corticotropin-releasing hormone and serotonin interact in the human brainstem: behavioral implications. Neuroscience 91, 1343–1354 (1999).

    Article  CAS  PubMed  Google Scholar 

  53. Blok, B. F. M., Willemsen, A. T. M. & Holstege, G. A PET study on brain control of micturition in humans. Brain 120, 111–121 (1997).

    Article  PubMed  Google Scholar 

  54. Rouzade-Dominguez, M. L., Curtis, A. L. & Valentino, R. J. Role of Barrington's nucleus in the activation of rat locus coeruleus neurons by colonic distension. Brain Res. 917, 206–218 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Pavcovich, L. A., Yang, M., Miselis, R. R. & Valentino, R. J. Novel role for the pontine micturition center, Barrington's nucleus: evidence for coordination of colonic and forebrain activity. Brain Res. 784, 355–361 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Klausner, A. P. & Steers, W. D. Corticotropin-releasing factor: a mediator of emotional influences on bladder function. J. Urol. 172, 2570–2573 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Klausner, A. P. et al. The role of corticotropin releasing factor and its antagonist, astressin, on micturition in the rat. Auton. Neurosci. 123, 26–35 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Kiddoo, D. A. et al. Impact of the state of arousal and stress neuropeptides on urodynamic function in the freely moving rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1697–R1706 (2006).

    Article  CAS  PubMed  Google Scholar 

  59. Kawatani, M., Suzuki, T. & de Groat, W. C. Corticotropin-releasing factor-like immunoreactivity in afferent projections to the sacral spinal cord of the cat. J. Auton. Nerv. Sys. 61, 218–226 (1996).

    Article  CAS  Google Scholar 

  60. LaBerge, J., Malley, S. E., Girard, B., Corrow, K. & Vizzard, M. A. Postnatal expression of corticotropin releasing factor (CRF) in rat urinary bladder. Auton. Neurosci. 141, 83–93 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. LaBerge, J., Malley, S. E., Zvarova, K. & Vizzard, M. A. Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R692–R703 (2006).

    Article  CAS  PubMed  Google Scholar 

  62. Saito, M., Longhurst, P. A., Tammela, T. L., Wein., A. J. & Levin, R. M. Effects of partial outlet obstruction of the rat urinary bladder on micturition characteristics, DNA synthesis and the contractile response to field stimulation and pharmacological agents. J. Urol. 150, 1045–1051 (1993).

    Article  CAS  PubMed  Google Scholar 

  63. Rickenbacher, E. et al. Impact of overactive bladder on the brain: central sequelae of a visceral pathology. Proc. Natl Acad. Sci. USA 105, 10589–10594 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. de Groat, W. C. & Yoshimura, N. Changes in afferent activity after spinal cord injury. Neurourol. Urodyn. 29, 63–76 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Bland, B. H. & Oddie, S. D. Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration. Behav. Brain Res. 127, 119–136 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. Kirby, R. S. The natural history of benign prostatic hyperplasia: what have we learned in the last decade? Urology 56, 3–6 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Tubaro, A. Defining overactive bladder: epidemiology and burden of disease. Urology 64, 2–6 (2004).

    Article  PubMed  Google Scholar 

  68. Mefford, I. N. & Potter, W. Z. A neuroanatomical and biochemical basis for attention deficit disorder with hyperactivity in children: a defect in tonic adrenaline mediated inhibition of locus coeruleus stimulation. Med. Hypotheses 29, 33–42 (1989).

    Article  CAS  PubMed  Google Scholar 

  69. Konrad, K., Gauggel, S. & Schurek, J. Catecholamine functioning in children with traumatic brain injuries and children with attention-deficit/hyperactivity disorder. Brain Res. Cogn. Brain Res. 16, 425–433 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Pliszka, S. R., McCracken, J. T. & Maas, J. W. Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J. Am. Acad. Child. Adolesc. Psychiatry 35, 264–272 (1996).

    Article  CAS  PubMed  Google Scholar 

  71. Shreeram, S., He, J. P., Kalaydjian, A., Brothers, S. & Merikangas, K. R. Prevalence of enuresis and its association with attention-deficit/hyperactivity disorder among U. S. children: results from a nationally representative study. J. Am. Acad. Child. Adolesc. Psychiatry 48, 35–41 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Griffiths, D. Clinical studies of cerebral and urinary tract function in elderly people with urinary incontinence. Behav. Brain Res. 92, 151–155 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Rovner, E. S. & Wein, A. J. Incidence and prevalence of overactive bladder. Curr. Urol. Rep. 3, 434–438 (2002).

    Article  PubMed  Google Scholar 

  74. Henry, J. P., Meehan, W. P. & Stephens, P. M. Role of subordination in nephritis of socially stressed mice. Contr. Nephrol. 30, 38–42 (1982).

    Article  CAS  Google Scholar 

  75. Lumley, L. A., Sipos, M. L., Charles, R. C., Charles, R. F. & Meyerhoff, J. L. Social stress effects on territorial marking and ultrasonic vocalizations in mice. Physiol. Behav. 67, 769–775 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Hoshaw, B. A., Evans, J. C., Mueller, B., Valentino, R. J. & Lucki, I. Social competition in rats: cell proliferation and behavior. Behav. Brain Res. 175, 343–351 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Wood, S. K., Baez, M. A., Bhatnagar, S. & Valentino, R. J. Social stress-induced bladder dysfunction: potential role of corticotropin-releasing factor. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1671–R1678 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Carrive, P. The periaqueductal gray and defensive behavior: functional representation and neuronal organization. Behav. Brain Res. 58, 27–47 (1993).

    Article  CAS  PubMed  Google Scholar 

  79. Blok, B. F. M. & Holstege, G. Direct projections from the periaqueductal gray to the pontine micturition center (M-region). An anterogreade and retrograde tracing study in the cat. Neurosci. Lett. 166, 93–96 (1994).

    Article  CAS  PubMed  Google Scholar 

  80. Chang, A. et al. Social stress in mice induces voiding dysfunction and bladder wall remodeling. Am. J. Physiol. Renal Physiol. 297, F1101–F1108 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Reyes, T. M., Walker, J. R., DeCino, C., Hogenesch, J. B. & Sawchenko, P. E. Categorically distinct acute stressors elicit dissimilar transcriptional profiles in the paraventricular nucleus of the hypothalamus. J. Neurosci. 23, 5607–5616 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sawchenko, P. E., Li, H. Y. & Ericsson, A. Circuits and mechanisms governing hypothalamic responses to stress: a tale of two paradigms. Prog. Brain Res. 122, 61–78 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Keay, K. A. & Bandler, R. Parallel circuits mediating distinct emotional coping reactions to different types of stress. Neurosci. Biobehav. Rev. 25, 669–678 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Abarbanel, J. & Marcus, E. L. Impaired detrusor contractility in community-dwelling elderly presenting with lower urinary tract symptoms. Urology 69, 436–440 (2007).

    Article  PubMed  Google Scholar 

  85. Varlam, D. E. & Dippell, J. Non-neurogenic bladder and chronic renal insufficiency in childhood. Pediatr. Nephrol. 9, 1–5 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. Fenster, H. & Patterson, B. Urinary retention in sexually abused women. Can. J. Urol. 2, 185–188 (1995).

    CAS  PubMed  Google Scholar 

  87. Bilanakis, N. Psychogenic urinary retention. Gen. Hosp. Psychiatry 28, 259–261 (2006).

    Article  PubMed  Google Scholar 

  88. Groutz, A. & Blaivas, J. G. Non-neurogenic female voiding dysfunction. Curr. Opin. Urol. 12, 311–316 (2002).

    Article  PubMed  Google Scholar 

  89. Feldman, A. S. & Bauer, S. B. Diagnosis and management of dysfunctional voiding. Curr. Opin. Pediatr. 18, 139–147 (2006).

    Article  PubMed  Google Scholar 

  90. Bauer, S. B. Special considerations of the overactive bladder in children. Urology 60, 43–49 (2002).

    Article  PubMed  Google Scholar 

  91. Ellsworth, P. I., Merguerian, P. A. & Copening, M. E. Sexual abuse: another causative factor in dysfunctional voiding. J. Urol. 153, 773–776 (1995).

    Article  CAS  PubMed  Google Scholar 

  92. Lettgen, B. et al. Urge incontinence and voiding postponement in children: somatic and psychosocial factors. Acta Paediatr. 91, 978–984 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Lettgen, B. et al. Urge incontinence and voiding postponement in children: somatic and psychosocial factors (discussion). Acta Paediatr. 91, 895–896 (2002).

    Article  Google Scholar 

  94. Davila, G. W., Bernier, F., Franco, J. & Kopka, S. L. Bladder dysfunction in sexual abuse survivors. J. Urol. 170, 476–479 (2003).

    Article  PubMed  Google Scholar 

  95. Romans, S., Belaise, C., Martin, J., Morris, E. & Raffi, A. Childhood abuse and later medical disorders in women. An epidemiological study. Psychother. Psychosom. 71, 141–150 (2002).

    Article  PubMed  Google Scholar 

  96. Franzen, K., Johansson, J. E., Andersson, G., Pettersson, N. & Nilsson, K. Urinary incontinence in women is not exclusively a medical problem: a population-based study on urinary incontinence and general living conditions. Scand. J. Urol. Nephrol. 43, 226–232 (2009).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge funding provided by an National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) George O'Brien Center Grant (PO5-DK052620-13) that was essential in facilitating discussions and collaborations between the neuroscientists and urologists involved in this Review.

Author information

Authors and Affiliations

  1. Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Civic Center Boulevard, Philadelphia, 19104, PA, USA

    Rita J. Valentino & Susan K. Wood

  2. Department of Surgery, The Children's Hospital of Philadelphia, Civic Center Boulevard, Philadelphia, 19104, PA, USA

    Stephen A. Zderic

  3. Division of Urology, University of Pennsylvania, Civic Center Boulevard, Philadelphia, 19014, PA, USA

    Alan J. Wein

Authors
  1. Rita J. Valentino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan K. Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan J. Wein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephen A. Zderic
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R. J. Valentino, S. K. Wood and S. A. Zderic researched data for the article, and R. J. Valentino wrote the article. All authors provided a substantial contribution to discussions of the content, and reviewed and edited the article before submission.

Corresponding author

Correspondence to Rita J. Valentino.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valentino, R., Wood, S., Wein, A. et al. The bladder–brain connection: putative role of corticotropin-releasing factor. Nat Rev Urol 8, 19–28 (2011). https://doi.org/10.1038/nrurol.2010.203

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2010.203

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing