Neurophysiology Of The Lower Urinary Tract

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

The micturition reflex is a finely tuned, coordinated neuromuscular event characterized by an orderly physiologic sequence. The two functions of the lower urinary tract are the storage of urine within the bladder and the timely expulsion of urine from the urethra. The storage and expulsion of urine are part of a complex neurophysiologic function that involves autonomic and somatic nervous systems. Function is controlled by reflex pathways, which are further modulated by central voluntary control. Precise knowledge of neuroanatomy, neurophysiology, and pharmacology is important to understand and treat many diseases of the lower urinary tract. The pelvis is no different from any other area of the body and nerve testing with nerve conduction studies, reflexes and electromyography (EMG) can be performed. Urinary incontinence currently affects 33 million American women. In the next 30 years the population over 60 years will increase by 80-90%. This will result in a tremendous increase in patients suffering this condition. Spinal cord injury is one of the most devastating conditions known to medicine with a prevalence of 2.3/100,000 population in the United Sates. It is therefore not feasible for evaluation and treatment to be limited to specialists. Primary care physicians must be comfortable performing basic evaluations which will enable them to formulate a diagnosis and conservative treatment plan.

The purpose of this article is to review normal function and neurologic control of the lower urinary tract in women. The nervous system is arranged into the central and the peripheral systems. The central nervous system includes the brain and spinal cord. Twelve paired cranial and 31 paired spinal nerves with their ganglia compose the peripheral nervous system. The somatic component of the peripheral system innervates skeletal muscle, and the autonomic division innervates skeletal muscle, and the autonomic division innervates cardiac muscle, smooth muscle, and glands. Historically, urologic complications were the main cause of death in spinal cord injury patients. Now their life expectancy is almost normal. Urodynamic diagnosis and guidance toward proper treatment is a key reason for the improved survival. Lifelong urologic surveillance is a central component to the routine care of the spinal cord injury patient. The article outlines neurologic pathways.

Mechanism of Normal Bladder Filling, Storage, and Voiding

Micturition is a complex interaction of the central and anatomic nervous systems. The main anatomic areas involved in voiding are the detrusor, the smooth muscle of the posterior urethra, the prostate (in men), and the striated muscle of the external sphincter. The nervous system is arranged into the central and the peripheral systems. The central nervous system includes the brain and spinal cord. Twelve paired cranial and 31 paired spinal nerves with their ganglia compose the peripheral system. The somatic component of the peripheral system innervates skeletal muscle, and the autonomic division innervates cardiac muscle, smooth muscle, and glands.

Central Nervous System: Within the brain and cord, nerve cell bodies are arranged in groups of various sizes and shapes called nuclei. Fibers with a common origin and destination are called a tract; some are so anatomically distinct that they are called fasciculus, brachium, peduncle, column, or lemniscus. Nerve cell bodies originating high in the central nervous system send axons to the motor nuclei in the brain stem and spinal cord to exert control over the cranial and spinal nerves. The control may be positive or inhibiting, but lesions of these tracts (upper motor neuron lesions) lead to opposite-body hyperreflexia and spastic weakness caused by a net reduction of inhibiting influences.

Peripheral Nervous System: The neuroanatomy involves the pelvic nerves (sacral parasympathetics), hypogastric nerves (thoracolumbar sympathetic nerves), and pudendal nerves (sacral somatic). Afferent input from the bladder with the sympathetic and parasympathetic nerves to reach cell bodies in the dorsal root ganglia at the thoracolumbar and sacral levels. Autonomic efferent fibers from the anterior section of the pelvic plexus travel up the lateral and posterior ligaments to provide bladder innervation. The bladder wall has many parasympathetic nerve endings. These nerve endings bind to acetylcholine (ACh), which is released by the parasympathetic system. Also, sparse sympathetic innervation is attributable to epinephrine and norepinephrine. A noncholinergic nonadrenergic component also innervates the bladder, but the most prevalent neurotransmitter is not yet known. Neurotransmitters such as substance P, vasoactive intestinal peptide, enkephalin, cholecystokinin, somatostatin, serotonin, y-amniobutyric acid, and neuropeptide Y have all been implicated in micturition. Furthermore, nitric oxide synthetase (NOS)-containing neurons have been identified in the bladder in the detrusor, where they may facilitate relaxation during micturition. In addition, afferent input to the urethra (eg, epinephrine, norepinephrine) that travels through the pelvic and pudendal nerves to the spinal cord can also result in sympathetic outflow from the thoracolumbar region. The adrenergic receptors of the urethra and bladder neck respond to norepinephrine (NE) released by the sympathetic nervous system which facilitates bladder storage and urinary incontinence. This is accomplished by relaxing the bladder body, where the beta-receptors are most prevalent, as well as by contracting the bladder outlet via the alpha-receptors. Beta-receptors (eg, beta-2), which result in smooth-muscle relaxation, appear along with the ACh receptors in the bladder body. Conversely, the alpha-receptors (eg, alpha-1) predominate in the bladder neck and proximal urethra, where they cause contraction when stimulated, in addition, the striated muscle of the pelvic floor serves as the external sphincter. It is innervated by the pudendal nerve, which originates from the sacral cord and uses acetylcholine (ACh) as its neurotransmitter.

Filling and Storage: During physiologic bladder filling, little or no increase in intravesical pressure is observed, despite large increases in urine volume. This process, is called accommodation, is caused primarily by passive elastic and viscoelastic properties of the smooth muscle and connective tissue of the bladder wall. During filling, muscle bundles in the bladder wall undergo reorganization, and the muscle cells are elongated up to four times their length. As bladder filling progresses and at a certain bladder wall tension, a desire to void is felt, although it has not been determined where in the brain this sensation is felt and processed.Mechanoreceptors in the bladder wall are activated, and action potentials run with afferent parasympathetic pelvic nerves to the spinal cord at the level of S2 to S4. As filling increases to a critical intravesical pressure, or with rapid bladder filling, detrusor muscle contractility is probably inhibited by activation of a spinal sympathetic reflex. The sympathetic efferents that influence micturition arise at the T10 through L2 area and synapse in the inferior mesenteric and pelvic ganglia. This reflex, with sensory afferent activity through the pelvic nerve and efferent activity the hypogastric nerve, results in inhibition of detrusor contractility and facilitation of bladder relaxation. Three sympathetic neural responses to afferent pelvic nerve firing associated with increasing bladder volume have been demonstrated experimentally: beta-receptor-mediated relaxation of the detrusor musculature, alpha-receptor-mediated increase in urethral smooth muscle activity and urethral pressure, and inhibition of ganglionic transmission in the pelvic (vesical) ganglia, which, in effect, inhibits sacral parasympathetic outflow to the bladder.

During bladder filling, outlet resistance increases by reflex stimulation of alpha-adrenergic receptors within the smooth muscle of the bladder neck and proximal urethra. In addition, stimulation of the striated external sphincter occurs, resulting from increased efferent somatic (pelvic and pudendal) nerve activity. Innervation of the proximal intramural portion of the striated urogenital sphincter (sphincter urethrae) is from somatic components of the pelvic nerve, via the pelvic plexus. Innervation of the distal striated urogenital sphincter (compressed urethrae and urethrovaginal sphincter) is via the pudendal nerve. These responses have been shown to both increase intraurethral pressure and inhibit pre-ganglionic detrusor motor neurons in the intermediolateral cell columns of the sacral spinal cord. The mechanisms responsible for switching reflexes from parasympathetic, sympathetic, and somatic pathways in the spinal cord.

Voiding: With filling to bladder capacity, stimuli from the bladder cause afferent discharges in the pelvic nerve, which traverse pathways in the spinal cord to synapse in a supraspinal micturition center in the pontine mesencephalic reticular formation. Voiding is initiated voluntarily or when the bladder volume is so large that it is no longer possible to suppress micturition. To initiate voiding, the external urethral sphincter relaxes voluntarily via somatic motor neurons from the ventral horn. Efferent impulses form the pontine micturition center run in the reticulospinal tracts to inhibit pudendal firing (relaxing the external sphincter) and to stimulate parasympathetic neurons situated in the inter-mediolateral cell column at levels S2 through S4, causing detrusor contraction. During voiding, sympathetic efferents are inhibited, which opens the bladder neck and permits post-ganglionic parasympathetic transmission. Brain stem modulation of micturition reflex allows for a detrusor contraction long enough to evacuate intravesical contents completely. With voluntary termination of voiding or with the stop test, the striated muscles of the urethra and pelvic floor contract to evaluate the bladder base, increase intraurethral pressure, and empty the urethra of urine. The detrusor muscle is reflexly inhibited and intravesical pressure returns to normal.

Clinical Applications:

The first recorded event of micturition is sudden and complete relaxation of striated sphincteric muscles, characterized by complete electrical silence of the sphincter EMG. This is followed almost immediately by an increase in detrusor pressure and concomitant decrease in urethral pressure as the bladder and proximal urethra become isobaric. The vesical neck and urethra open and voiding ensues. The reflex is normally under voluntary control and is organized in the rostral brain stem (the pontine micturition center). It requires integration and modulation by the parasympathetic and somatic components of the sacral spinal cord (the sacral micturition center) and the thoracolumbar sympathetics.

The locations of certain possible nervous lesions are denoted by numbers and explained as follows:

  1. Lesions isolating the superior frontal gyrus prevent voluntary postponement of voiding. If sensation is intact, this produces urge incontinence. If the lesion is larger, there is additional loss of social concern about incontinence.
  2. Lesions isolating the paracentral lobule, sometimes associated with a hemiparesis, cause spasticity of the urethral sphincter and retention. This is painless if sensation is abolished. Minor degrees of this syndrome may cause difficulty in the initiation of micturition.
  3. Pathways of sensation are not known accurately. In theory, an isolated lesion of sensation above the brain stem would lead to unconscious incontinence. Defective central conduction of sensory information would explain nocturnal enuresis.
  4. Lesions above the brain stem centers lead to involuntary voiding that is coordinated with sphincter relaxation.
  5. Lesions below brain stem centers but above the lumbosacral spinal cord lead, after a period of bladder paralysis associated with spinal shock, to involuntary reflex voiding that is not coordinated with sphincter relaxation (detrusor/sphincter dyssynergia).
  6. Lesions destroying the lumbosacral cord or the complete nervous connections between the central and peripheral nervous system result in a paralyzed bladder that contracts only weakly in an autonomous fashion because of remaining ganglionic innervation. However, if the lumbar sympathetic outflow is preserved in the presence of conus or cauda equine destruction, then there may be some residual sympathetic tone in the bladder neck and urethra that may be sufficient to be obstructive.
  7. A lesion of the efferent fibers alone leads to a bladder of decreased capacity and decreased compliance associated experimentally with an increased number of adrenergic nerves.
  8. A lesion confined to the afferent fibers produces a bladder that is areflexic with increased compliance and capacity.
  9. Because there are ganglion cells in the bladder wall, it is technically impossible to decentralize the bladder completely, but congenital absence of bladder ganglia may exist, producing megacystis.

Cortical Lesions: The only region of the cerebral cortex consistently associated with detrusor dysfunction when damaged is the superior frontal gyrus-septal area. Lesions in this area interfere with voluntary inhibition of the pontine detrusor reflex center. Urodynamic and electrophysiologic testing show detrusor hyperreflexia with contractions, which are coordinated with urethral relaxation and decreased surface EMG activity. Cortical lesions may prevent voluntary postponement of voiding. Urge incontinence results when sensation is intact. If sensation is not intact, involuntary voiding (enuresis) occurs. With larger lesions, social concern about incontinence is lost. A separate cortical area regulates upper motor control of the pudendal nerve. This pudendal nucleus is located in paracentral lobule cortical areas. Lesions here may be involved with hemiparesis and may produce upper motor neuron findings with contralateral extensor plantar reflexes and increased deep tendon reflexes. These lesions can be characterized electrophysiologically by inability to quiet electrical activity in the pelvic floor, as measured by loss of voluntary influence on electromyelography amplitude reflex, failure to suppress sphincter EMG activity during voiding, or more simply by exaggerated surface EMG perineal musculature activity. This exaggeration and spasticity may be associated with difficulty in initiating micturition. This paracentral lobule syndrome is uncommon.

Suprasacral and Sacral Cord Areas: The nature of a voiding or urinary storage disturbance that occurs with spinal cord disease depends on the site and extent of the injury, type of recovery, and presence or absence of other neurologic or urogynecologic disorders. Lower urinary tract neurons with long ascending axons reach the pons micturition area to mediate chiefly facilitative effects. These axons enter sacral posterior roots and pass in the spinothalamic and posterior spinal tracts. Lesions affecting these compartments can lead to detrusor areflexia and increased compliance. Correspondingly, intentional sectioning (sacral dorsal rhizotomy) prevents bladder contractions and increases capacity. Effector pathways from the pons to the lower cord are chiefly inhibitory, and lesions affecting these cord areas lead to small non-amplified, poorly coordinated detrusor contractions of short duration, with resultant increased residual urine. Hence, higher cord lesions vary in clinical manifestations. Neurophysiologic studies in patients with suprasacral spinal cord disease may demonstrate normal peripheral and prolonged total and central conduction times. Urodynamic studies document detrusor hyperreflexia, with or without detrusor-sphincter dyssynergia, depending on the lesion. Electromyelography and sphincter EMG studies often do not show abnormalities, although facilitation of the elcetromyelographic reflex response and lack of volitional control over it could be expected. Deep tendon hyperreflexia and impaired lower extremity sensation may be found on physical examination.

Sacral Cord Area: Lesions involving the sacral cord lead to lower motor neuron disorders with possible absence of both detrusor and urethral sphincter activity. Causes include tumor, arachnoiditis, and trauma. Symmetric saddle distribution of sensory loss, sensory dissociation, and mild lower limb motor loss without atrophy are found. The incontinence is usually due to poor bladder volume tolerance, coupled with abnormal urethral function. Obstruction to the incontinence (as by anti-incontinence surgery) may place the upper tracts in jeopardy. Findings in these patients include trabeculations on cystoscopy, positive bethanechol super-sensitivity test, abnormal sphincter EMG (lower motor neuron disease), usually abnormal electromyelography, decreased sensation, and prolonged peripheral and total conduction times.

Cauda Equina: Clinically, in most patients with cauda equine injury is a result of vertebral injury below T12 or intervertebral disk protrusion usually in the L4-L5 or L5-S1 spaces. The saddle distribution of sensory loss is less symmetric than with sacral cord lesions, and sensory dissociation is absent. Elevated postvoid residual volumes and occasional urinary retention are common. Urodynamic studies show abdominal-type voiding, absent detrusor activity, abnormal sphincter EMG, and abnormal electromyelography with prolonged peripheral conduction times. Bethanechol super-sensitivity test is usually positive. Electrophysiologic testing of the lower limbs as well as the nerves to the pelvis is necessary to assist in the diagnosis of cauda equine and sacral cord syndromes.

Pelvic Plexus Injury: The pelvic plexus may be affected by surgical procedures involving the lower colorectal or gynecologic systems. The pelvic plexus contains sympathetic postganglionic, parasympathetic preganglionic, visceral afferent, and some sacral somatic nerves. Patients with pelvic plexus injury do not have noticeable perineal sensory loss. Sensory disturbances may be seen in the bladder when damage occurs to the afferent innervation through autonomic nerves in the pelvic plexus, thus increasing the micturition threshold. Pelvic plexus injury may lead to parasympathetic denervation and detrusor areflexia, occasionally with markedly decreased compliance. Complicating this situation, alpha-adrenergic denervation leads to incompetency at the bladder neck so that incontinence may be associated with the frustrating difficulty in initiating urination. Thus, there is decreased bladder compliance, detrusor hypoactivity, incompetence of the bladder neck, and diminished urethral closure pressures. Electromyelography generally is abnormal. Clitoral anal reflex and perineal and pudendal terminal motor latencies generally are unaffected, being beyond the area of injury. Pelvic plexus injury may be associated with hyposensitivity in the bladder and urethra. Sphincter EMG is variable depending on whether the nerve supply is through direct pelvic plexus somatic nerve or pudendal pathways.

Distal Pudendal Neuropathy: With the advent of pudendal and perineal nerve terminal motor latency studies, single-fiber density studies, and other sphincter EMG studies, there is increased appreciation of the significance of distal pudendal nerve injury. It is strongly related both to urinary and fecal incontinence and to pelvic organ prolapse. The association of changes in latency with EMG changes in the sphincters can demonstrate neuropathy. 20% to women show such changes after vaginal delivery. The strong relationship between pudendal neuropathy and genuine stress incontinence and anal incontinence suggests possible methods for prevention of these disorders.


Our understanding of the neurophysiology of micturition developed from a large body of literature based primarily on animal models. The detrusor and the periurethral striated muscle mechanisms have separate cortical and other higher-center regulation. The effects of such regulation are chiefly on the brain-stem for the detrusor and on the sacral cord for the periurethral mechanisms. Pudendal cortical pathways affect periurethral striated muscle innervation by direct descending paths originating in the central vertex of the pudendal cerebral cortical area and going to pudendal nuclei in the ventromedial portion of the ventral gray matter of the S1 to S3 cord segments. Patients demonstrating persistence of distal pudendal neurophysiologic abnormality after vaginal delivery, change in management of subsequent deliveries may be considered to prevent the profound sequelae of pelvic floor neuropathy in later years. Detrusor-external sphincter dyssynergia is characterized by involuntary contractions of the striated musculature of the urethral sphincter during an involuntary detrusor contraction. Neurologic lesions above the pons usually leave the "micturition reflex" intact, and they result in loss of voluntary control of the micturition reflex. Interruption of the neural pathways connecting the "pontine micturition center" to the "sacral micturition center" usually results in detrusor external sphincter dyssynergia. Sacral neurologic lesions have a variable effect on micturition depending on the extent to which the neurologic injury affects the parasympathetic, sympathetic, and somatic systems. Somatic neurologic lesions affect pudendal afferents and efferents. In addition to loss of perineal and peri-anal sensation, these lesions abolish the bulbocavernosus reflex, and impair the ability to voluntarily contract the urethral and anal sphincters. Sacral neurologic lesions are caused by herniated discs, diabetic neuropathy, multiple sclerosis, and spinal cord tumors. They are also commonly encountered after extensive pelvic surgery, such as abdomino-perineal resection of the rectum and radical hysterectomy.

Suggested Reading:

  1. Abrams P, Cardozo L, Khoury S, Wein A. editors. Incontinence, 2nd edition. Plymouth, UK: Health Publication Ltd; 2002 (Level III)
  2. Associations of Professors of Gynecology and Obstetrics. Clinical management of urinary incontinence. Crofton (MD): APGO; 2004 (Level III)
  3. Hay-Smith EJ, Bo K, Berghamans LC et al. Pelvic floor muscle training for urinary incontinence in women. The Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No: CD001407, DOI: 10.1002/14651858. CD 001407 (Meta-analysis)
  4. ACOG Practice Bulletin. Urinary incontinence in women. Number 63, June 2005
  5. Doughty DB. Editor. Urinary & fecal incontinence. 3rd edition. Mosby 2006
  6. Chapple CR, Zimmern PE, Brubaker K, Smith ARB, Bo k. editors. Multidisciplinary management of female pelvic floor disorders. Mosby / Saunders 2006
  7. Scientific Committee of the First International Consultation on Incontinence. Assessment and treatment of urinary incontinence. Lancet 2000; 355:2153-2158 (Level III)
  8. Karram MM, Walters MD. Urogynecology and reconstructive pelvic surgery. Third Editions. St. Louis: Mosby, 2007.
  9. Blaivas J, Chancellor M. Atlas of urodynamics. Baltimore: William & Wilkins, 2007.
  10. Hunskaar S, Arnold EP, Burgio K et al. Epidemiology and natural history of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11:301-319
  11. Otcenasek M, Baca V, Krofta L et al. Endopelvic fascia in women. Obstet Gynecol 2008;111:622-630

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