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  • Review Article
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The neural control of micturition

Key Points

  • The lower urinary tract is innervated by a complex system of autonomic and somatic nerves, the former of which control the smooth muscle of the bladder and the urethra and the latter of which activate the striated sphincter. Afferent fibres travel with the parasympathetic, sympathetic and somatic nerves.

  • The recent discovery of the sensory properties of the urothelium has triggered an intensive investigation into the importance of neural–urothelial interactions in health and disease states.

  • Multiple CNS pathways that carry information between the brain and the spinal cord are involved in the regulation of the lower urinary tract.

  • The neural organization that controls bladder filling and maintains continence through the guarding reflex is organized within the spinal cord. However, voluntary voiding, a central part of human behaviour, is dependent on complex neural pathways in the brain that have been identified with functional brain-imaging techniques.

  • The periaqueductal grey (PAG) receives sensory input from the bladder and seems to have a central role in both registering the extent of bladder fullness and controlling the initiation of voiding. The PAG makes multiple connections with many other brain areas, including the pontine micturition centre (PMC), the thalamus, the prefrontal cortex and the insula.

  • During urine storage, the PAG relays bladder filling information to higher centres, and might participate in the tonic suppression of voiding. During voiding, PMC suppression is interrupted by activity in the prefrontal cortex and the hypothalamus. Excitation of the PMC then activates descending pathways to the spinal cord that cause sequential urethral relaxation and contraction of the detrusor.

  • During postnatal development, the maturation of central neural pathways leads to the downregulation of reflex voiding and the emergence of voluntary voiding mechanisms. However, primitive voiding reflexes can re-emerge following neural injury.

  • A full understanding of the pathophysiological changes and neuroplasticity that underlie idiopathic detrusor overactivity, cystitis and painful bladder conditions has yet to be elucidated, although recent progress has been made.

  • New therapies for the treatment of detrusor overactivity include vanilloids and, most recently, detrusor injection of botulinum toxin A.

Abstract

Micturition, or urination, occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. The neural circuitry that controls this process is complex and highly distributed: it involves pathways at many levels of the brain, the spinal cord and the peripheral nervous system and is mediated by multiple neurotransmitters. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary or reflex micturition, leading to urinary incontinence. This is a major health problem, especially in those with neurological impairment. Here we review the neural control of micturition and how disruption of this control leads to abnormal storage and release of urine.

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Figure 1: Efferent pathways of the lower urinary tract.
Figure 2: A model illustrating possible chemical interactions between urothelial cells, afferent nerves, efferent nerves and myofibroblasts in the urinary bladder.
Figure 3: Primary afferent and spinal interneuronal pathways involved in micturition.
Figure 4: Connections between the lumbosacral spinal cord and brain areas involved in bladder control.
Figure 5: Neural circuits that control continence and micturition.
Figure 6: Brain areas involved in the regulation of urine storage.
Figure 7: Reflex voiding responses in an infant, a healthy adult and a paraplegic patient.
Figure 8: Organization of the parasympathetic excitatory reflex pathway to the detrusor muscle.

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Acknowledgements

Supported by US National Institutes of Health grants DK049430 and DK077783 to W.D. C.F.'s contribution to this work was undertaken at University College London Hospital/University College London, who received a proportion funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme.

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Correspondence to Clare J. Fowler.

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William C. de Groat has personal stock in Pfizer Pharmaceuticals Inc. He is also on the Scientific Advisory Boards of Allergan Inc. and Dynogen Inc.

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FURTHER INFORMATION

Derek Griffiths' homepage

Glossary

Pudendal nerve

A nerve that innervates the external genitalia and the urethral and anal sphincters.

Detrusor muscle

The smooth muscle of the bladder.

Onuf's nucleus

A nucleus in the sacral cord that contains the anterior horn cells that innervate the sphincters.

Urothelium

The superficial layer of the bladder.

Intravesical

Inside the bladder.

Detrusor overactivity

In humans, involuntary detrusor contractions during bladder filling; in experimental animals, non-voiding detrusor contractions.

Myofibroblast

A cell that has some characteristics of a fibroblast and some characteristics of a smooth-muscle cell; also known as an interstitial cell.

Urethral reflexes

Involuntary autonomic and somatic neural mechanisms that control the urethral muscles.

Urgency incontinence

Loss of urine that is immediately preceded by or accompanied by the sensation of urgency.

Myogenic

Of muscle origin.

Ice-water test

A test for bladder function in which ice water is instilled into the bladder to cause reflex detrusor contraction.

4-aminopyridine

A molecule that is used to characterize subtypes of K+ channel.

Heteropodatoxin

A peptide that blocks voltage-gated K+ channels.

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Fowler, C., Griffiths, D. & de Groat, W. The neural control of micturition. Nat Rev Neurosci 9, 453–466 (2008). https://doi.org/10.1038/nrn2401

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