The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.

https://www.physiology.org/doi/pdf/10.1152/physrev.00038.2003

Urinary bladder contraction and relaxation: Physiology and pathophysiology

A myogenic basis for the overactive bladder

Science of urinary incontinence

The lower urinary tract constitutes a functional unit controlled by a complex interplay between the central and peripheral nervous systems and local regulatory factors. In the adult, micturition is controlled by a spinobulbospinal reflex, which is under suprapontine control. Several central nervous system transmitters can modulate voiding, as well as, potentially, drugs affecting voiding; for example, noradrenaline, GABA, or dopamine receptors and mechanisms may be therapeutically useful. Peripherally, lower urinary tract function is dependent on the concerted action of the smooth and striated muscles of the urinary bladder, urethra, and periurethral region. Various neurotransmitters, including acetylcholine, noradrenaline, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in this neural regulation. Muscarinic receptors mediate normal bladder contraction as well as at least the main part of contraction in the overactive bladder. Disorders of micturition can roughly be classified as disturbances of storage or disturbances of emptying. Failure to store urine may lead to various forms of incontinence, the main forms of which are urge and stress incontinence. The etiology and pathophysiology of these disorders remain incompletely known, which is reflected in the fact that current drug treatment includes a relatively small number of more or less well-documented alternatives. Antimuscarinics are the main-stay of pharmacological treatment of the overactive bladder syndrome, which is characterized by urgency, frequency, and urge incontinence. Accepted drug treatments of stress incontinence are currently scarce, but new alternatives are emerging. New targets for control of micturition are being defined, but further research is needed to advance the pharmacological treatment of micturition disorders.

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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Neural Control of the Lower Urinary Tract

Bladder Outflow Obstruction—A Cause of Denervation Supersensitivity

Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction.

Specific clinical criteria have been used to diagnose interstitial cystitis in 32 patients. The distribution of mast cells in biopsies of the bladder wall from these patients has been compared with that of similar cells in control specimens. A highly significant increase (P less than 0.001) in the number of mast cells within the detrusor muscle bundles has been demonstrated in 27 of these patients. This mast cell infiltration is widespread throughout the detrusor muscle and is not confined to the ulcerative lesions seen cystoscopically. Histological estimation of mast cells is of value, therefore, in establishing the diagnosis of interstitial cystitis, and may be particularly helpful in equivocal cases. The relationship between mast cell infiltration of the detrusor muscle bundles and the aetiology of the disease remains to be determined.

Mast Cells in Interstitial Cystitis

Summary— Quantitative methods have been used to assess the amount of autonomic nerve in bladder biopsy samples from a group of “control” patients ranging in age from 20 to 79 years. Each patient included in the study was urodynamically normal and showed no subjective evidence of bladder trabeculation at cystoscopy. Using light microscopy, a significant linear reduction in the amount of acetylcholinesterase-positive nerve was observed with increasing age. Counts of axon profiles and measurement of smooth muscle cell cross-sectional areas in the electron microscope revealed a similar reduction in the amount of nerve per mm2 of detrusor muscle tissue. These findings thus confirm that a real reduction in the number of nerve axons occurs with age and the light microscope results are not due merely to a reduction in the amount of nerve-associated acetylcholinesterase.

The present study provides baseline data for future comparisons of the density of autonomic innervation in bladders which are functionally impaired.

C.J. Gilpin

Papers

Bladder Outflow Obstruction—A Cause of Denervation Supersensitivity

Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction.

Mast Cells in Interstitial Cystitis

The effect of age on the autonomic innervation of the urinary bladder.

Electron Microscopic Investigation of the Bladder Urothelium and Glycocalyx in Patients with Interstitial Cystitis