Onuf's nucleus

Last updated
Onuf's nucleus
Medulla spinalis - Substantia grisea - English.svg
Spinal cord - grey matter (Onuf's nucleus not labeled, but region is visible)
Details
Identifiers
Latin nucleus nervi pudendi
TA98 A14.1.02.139
TA2 6084
FMA 77024
Anatomical terminology

Onuf's nucleus is a distinct group of neurons located in the ventral part (lamina IX) of the anterior horn of the sacral region of the human spinal cord involved in the maintenance of micturition and defecatory continence, as well as muscular contraction during orgasm. It contains motor neurons, and is the origin of the pudendal nerve. The sacral region of the spinal cord is the fourth segment (cervical, thoracic, and lumbar being the first three) of vertebrae in the spinal cord which consists of the vertebrae 26-30. [1] While working in New York City in 1899, Bronislaw Onuf-Onufrowicz discovered this group of unique cells and originally identified it as “Group X.” “Group X” was considered distinct by Onufrowicz because the cells were different in size from the surrounding neurons in the anterolateral group, suggesting that they were independent. [2]

Contents

Structure

Onuf's nucleus is a distinct group of neurons located in the ventral part (lamina IX) of the anterior horn of the sacral region of the human spinal cord involved in the maintenance of micturition and defecatory continence, as well as muscular contraction during orgasm. It contains motor neurons, and is the origin of the pudendal nerve. The sacral region of the spinal cord is the fourth segment (cervical, thoracic, and lumbar being the first three) of vertebrae in the spinal cord which consists of the vertebrae 26-30. [1]

This small group of neural cells is located between S1 and S2 or S2 and S3 and although Onuf's nucleus is located primarily in S2, it can extend to the caudal end of the first sacral segment or to the middle part of the third sacral segment. Also, Onuf's nucleus is found almost symmetrically on both sides of the ventral horn. This innervation, or nerve supply, is arranged in a neuropil and averages approximately 625 neurons in both the left and right ventral horns, [3] and measures about 4–6 mm on each side. [4] In other animals it averages approximately 300-500 on both sides. [3]

Many staining techniques have been used to study the anatomy of Onuf's nucleus. The Nissl method was commonly used as well as myelin sheath stains and silver stains. Use of the Klüver-Barrera staining method showed that Onuf's nucleus appears clear due to the presence of many vertically arranged unmyelinated fibers. The sizes of the cells in Onuf's nucleus are small in comparison to other lateral group cells. The neurons in Onuf's nucleus are motoneurons, and like most motoneurons they are characterized by their multipolarity and large Nissl bodies. [1]

Function

Onuf's nucleus is the origin of innervation for the striated muscles of the rectum and urethral sphincters. The neurons of Onuf's nucleus are responsible for controlling external sphincter muscles of the anus and urethra in humans. Onufrowicz also proposed that Onuf's nucleus controlled the ischiocavernosus and bulbocavernosus muscles which function in penile erection and ejaculation in males. The dorsomedial subnucleus innervates the external anal sphincter and the ventrolateral subgroup connects to the external urethral sphincter. [1] [3] [5]

Somatic

Autonomic

Neurotransmitters in Onuf's nucleus

The motoneurons in Onuf's nucleus contain a dense array of serotonin and norepinephrine receptors and neurotransmitters and are activated by glutamate. When the 5-HT and NE receptors are stimulated, the guarding reflex occurs to prevent voiding of the bladder caused by unexpected abdominal pressure. [7]

Sexual dimorphism

Onuf's nucleus is sexually dimorphic, meaning that there are differences in Onuf's nucleus between males and females of the same species. Sexual dimorphism of Onuf's nucleus has been found in dogs, monkeys, and humans. Males of these species have more of these motoneurons than do their female counterparts. It has also been shown that the sex differences in Onuf's nucleus can be reduced (or in some cases eliminated) by exposing a prenatal female to high levels of androgen. [8] [9] [10]

Clinical significance

Urinary stress incontinence

Stress urinary incontinence (SUI) is a common disease in women caused by pelvic floor muscle weakness. Coughing, laughing, sneezing, exercising or other movements that increase intra-abdominal pressure, and thus increase pressure on the bladder, are common reasons for urine loss.

There are three layers of muscle that are known to control urine flow through the urethra; an inner band of longitudinal smooth muscle, a middle band of circular smooth muscle, and an external band of striated muscle called the rhabdosphincter. The urethra is controlled by the sympathetic, parasympathetic, and somatic divisions of the peripheral nervous system. The sympathetic innervation (nerve supply) comes from the sympathetic preganglionic neurons located in the upper lumbar spinal cord along the hypogastric nerve and terminates in the longitudinal and circular smooth muscle layers in the urethra. The parasympathetic nerve supply comes from the parasympathetic preganglionic neurons in the sacral spinal cord and also terminates in the longitudinal and circular smooth muscle layers. Finally the somatic nerve supply arises from the urethral sphincter motor neurons in the ventral horn of the sacral spinal cord; better known as Onuf's nucleus. The pudendal nerve that extends from Onuf's nucleus, connects directly to the rhabdosphincter muscle to control micturation.

The sympathetic storage reflex or pelvic-to-hypo-gastric reflex is initiated when the bladder swells. Stretch receptors cause postganglionic neurons to release norepinephrine (NE). NE causes the bladder to relax and the urethra to contract, thus preventing urine loss. The somatic storage reflex or the pelvic-to-pudendal or guarding reflex is initiated when one laughs, sneezes, or coughs, which causes increased bladder pressure. Glutamate is the primary excitatory transmitter for the reflex. Glutamate activates NMDA and AMPA receptors which produce action potentials. These action potentials activate the release of acetylcholine causing the rhabdosphincter muscle fibers to contract. When the guarding reflex does not function normally, SUI occurs. [7]

Duloxetine

Onuf's nucleus controls rhabdosphincter motor neurons and has been shown to contain a dense array of 5-HT (serotonin) and NE terminals. 5-HT and NE were shown to inhibit bladder activity. In 2005, researchers Wolfgang H. Jost and Parvaneh Marsalek used serotonin norepinephrine reuptake inhibitors (SNRI) to increase the synaptic levels of both 5-HT and NE in the synaptic cleft. Duloxetine hydrochloride, a SNRI, has been shown to increase bladder capacity and sphincteric muscle activity in animals and humans exhibiting irritated bladder function. Duloxetine is the first medication developed to help SUI. This is promising because Duloxetine also showed no effect on bladder contraction force or duration which suggests that Duloxetine is affecting the sensory limb of the urination process. 5-HT and NE do not function through direct excitation of motor neurons but facilitate the effects of glutamate. When glutamatergic activation in sphincter motor neurons is absent there is no effect of NE or 5-HT (seen during micturition contraction). [3]

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis ( Lou Gehrig disease ) is a disease that causes degeneration of motoneurons that control voluntary muscle movement. Surprisingly, the bladder and rectum sphincters remain normal even during the final terminal stages of the illness. Since these muscles are controlled by Onuf's nucleus, it is of great importance in the study of this disease. In amyotrophic lateral sclerosis, Onuf's nucleus is preserved but the other anterior horn cell groups atrophy. This discovery reinforced the notion that Onuf's nucleus controlled the muscles related to sphincter function in the anus and urethra.

In a study conducted by Kihira et al., eight individuals with amyotrophic lateral sclerosis were compared to nine control cases. The results indicated that the total number of neurons in Onuf's nucleus in patients with amyotrophic lateral sclerosis did not differ from the control patients. However, normal neurons decreased in number while atrophic neurons increased. It was also shown that the decrease in the number of normal neurons was not due to aging. Patients with amyotrophic lateral sclerosis also contain less RNA in their motoneurons than normal individuals. The decrease in RNA is correlated with the decrease in size of the nucleolus. Thus, the size of the nucleolus may be an early indicator of amyotrophic lateral sclerosis. [6]

There is often sparing of Onuf's nucleus in spinal muscular atrophy type 1. [11]

Shy–Drager syndrome

In order to study Onuf's nucleus from the opposite perspective (meaning cases where it was not preserved) studies were done on Shy–Drager syndrome. Shy–Drager syndrome is a rare neurodegenerative disease that attacks the autonomic nervous system. Since the main symptom of Shy–Drager syndrome is incontinence it makes it a good candidate to study its effects on Onuf's nucleus. When the sacral sections of the spinal cord were studied in patients with Shy–Drager syndrome, it was revealed that cell death was confined to the area of Onuf's nucleus. This, once again, verified the role Onuf's nucleus in vesicorectal function. [12]

History

While working in New York City in 1899, Bronislaw Onuf-Onufrowicz discovered this group of unique cells and originally identified it as “Group X.” “Group X” was considered distinct by Onufrowicz because the cells were different in size from the surrounding neurons in the anterolateral group, suggesting that they were independent. [2]

Other animals

Onuf's nucleus is not specific only to humans. As mentioned before, the motor neurons of the external urethral sphincter and the external anal sphincter are found in ventral horn of the second sacral segment known as Onuf's nucleus. Using horseradish peroxidase to stain the neurons, it has been determined that the external anal sphincter motoneurons are located in dorsomedial to the external urethral sphincter motoneuron in the cat, dog, monkey, golden hamster, as well as the man. However, the location of these motoneurons differs in the rat, Mongolian gerbil and domestic pig. In the rat, these motoneurons are located in separate cell groups. [13]

In addition to differences among location of the motoneurons responsible or sphincter function, it is important to mention the differences in sexual dimorphism between species. Although sexual dimorphism of Onuf's nucleus is present in all species, the extent of the sexual dimorphism varies. For example, sexual dimorphism in the number of perineal motoneurons is less obvious in dogs and humans than it is in rats. This is to be expected because female dogs retain perineal muscles whereas female rats do not have perineal muscles. As in humans, prenatal androgen plays an important role in establishing the sex differences in Onuf's nucleus of these species. If a female is exposed to excess androgen during the prenatal period, the sexual dimorphism does not occur in Onuf's nucleus. [9]

Notes

  1. 1 2 3 4 Mannen, T (2000). "Neuropathological findings of Onuf's nucleus and its significance". Neuropathology. 20: S30–S3. doi:10.1046/j.1440-1789.2000.00298.x. PMID   11037184. S2CID   37675034.
  2. 1 2 Onufronwicz B (1899), "Notes on the arrangement and function of the cell groups of the sacral region of the spinal cord", J Nerv Ment Dis, 26 (8): 498–504, doi:10.1097/00005053-189908000-00006, S2CID   147602936.
  3. 1 2 3 4 Jost WH, Marsalek P (2005), "Duloxetine in the treatment of stress urinary incontinence", Therapeutics and Clinical Risk Management, 1 (4): 259–264, PMC   1661641 , PMID   18360568.
  4. Scaravilli T, Pramstaller PP, Salerno A, Egarter-Vigl E, Giometto B, et al. (2000), "Neuronal loss in Onuf's nucleus in three patients with progressive supranuclear palsy", Annals of Neurology, 48 (1): 97–101, doi:10.1002/1531-8249(200007)48:1<97::AID-ANA14>3.0.CO;2-Z, PMID   10894221.
  5. 1 2 3 4 5 6 Bergmann, M.; Völpel, M.; Kuchelmeister, K. (April 1995). "Onuf's nucleus is frequently involved in motor neuron disease/amyotrophic lateral sclerosis". Journal of the Neurological Sciences. 129 (2): 141–146. doi:10.1016/0022-510x(94)00263-n. PMID   7608728. S2CID   46435725.
  6. 1 2 3 Kihira T, Yoshida S, Yoshimasu F, Wakayama I, Yase Y (1997), "Involvement of Onuf's nucleus in amyotrophic lateral sclerosis", Journal of the Neurological Sciences, 147 (1): 81–88, doi:10.1016/S0022-510X(96)05313-0, PMID   9094064, S2CID   13646314.
  7. 1 2 Thor, KB (2004). "Targeting serotonin and norepinephrine receptors in stress urinary incontinence". International Journal of Gynecology & Obstetrics. 86: S38–S52. doi: 10.1016/j.ijgo.2004.04.028 . PMID   15302566. S2CID   24259615.
  8. Forger, Nancy G.; Frank, Laurence G.; Breedlove, S. Marc; Glickman, Stephen E. (11 November 1996). "Sexual dimorphism of perineal muscles and motoneurons in spotted hyenas". The Journal of Comparative Neurology. 375 (2): 333–343. doi: 10.1002/(SICI)1096-9861(19961111)375:2<333::AID-CNE11>3.0.CO;2-W . PMID   8915834.
  9. 1 2 Forger, N. G.; Breedlove, S. M. (1 October 1986). "Sexual dimorphism in human and canine spinal cord: role of early androgen". Proceedings of the National Academy of Sciences. 83 (19): 7527–7531. Bibcode:1986PNAS...83.7527F. doi: 10.1073/pnas.83.19.7527 . PMC   386752 . PMID   3463982.
  10. Forger, N. G.; Breedlove, S. M. (1 October 1986). "Sexual dimorphism in human and canine spinal cord: role of early androgen". Proceedings of the National Academy of Sciences. 83 (19): 7527–7531. Bibcode:1986PNAS...83.7527F. doi: 10.1073/pnas.83.19.7527 . PMC   386752 . PMID   3463982.
  11. Prayson R, Neuropathology Review, 2nd edition. page 62.
  12. Mannen, T.; Iwata, M.; Toyokura, Y.; Nagashima, K. (1982). "The Onuf's nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome". Acta Neuropathologica. 58 (4): 255–260. doi:10.1007/BF00688606. PMID   7158303. S2CID   24212217.
  13. Gerrits, Peter O; Sie, Judith A.M.L; Holstege, Gert (May 1997). "Motoneuronal location of the external urethral and anal sphincters: a single and double labeling study in the male and female golden hamster". Neuroscience Letters. 226 (3): 191–194. doi:10.1016/S0304-3940(97)00279-6. PMID   9175599. S2CID   42499162.

Related Research Articles

<span class="mw-page-title-main">Urethra</span> Tube that connects the urinary bladder to the external urethral orifice

The urethra is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both female and male mammals. In female humans and other primates, the urethra connects to the urinary meatus above the vagina.

<span class="mw-page-title-main">Pudendal nerve</span> Main nerve of the perineum

The pudendal nerve is the main nerve of the perineum. It is a mixed nerve and also conveys sympathetic autonomic fibers. It carries sensation from the external genitalia of both sexes and the skin around the anus and perineum, as well as the motor supply to various pelvic muscles, including the male or female external urethral sphincter and the external anal sphincter.

<span class="mw-page-title-main">Urination</span> Release of urine from the urinary bladder

Urination is the release of urine from the bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, or, rarely, emiction, and known colloquially by various names including peeing, weeing, pissing, and euphemistically going number one. In healthy humans and other animals, the process of urination is under voluntary control. In infants, some elderly individuals, and those with neurological injury, urination may occur as a reflex. It is normal for adult humans to urinate up to seven times during the day.

<span class="mw-page-title-main">Urinary incontinence</span> Uncontrolled leakage of urine

Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geriatric health care. The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis. UI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others.

<span class="mw-page-title-main">Parasympathetic nervous system</span> Division of the autonomic nervous system

The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

Articles related to anatomy include:

<span class="mw-page-title-main">External sphincter muscle of male urethra</span>

The external sphincter muscle of male urethra, also sphincter urethrae membranaceae, sphincter urethrae externus, surrounds the whole length of the membranous urethra, and is enclosed in the fascia of the urogenital diaphragm.

<span class="mw-page-title-main">Bladder sphincter dyssynergia</span> Medical condition

Bladder sphincter dyssynergia is a consequence of a neurological pathology such as spinal injury or multiple sclerosis which disrupts central nervous system regulation of the micturition (urination) reflex resulting in dyscoordination of the detrusor muscles of the bladder and the male or female external urethral sphincter muscles. In normal lower urinary tract function, these two separate muscle structures act in synergistic coordination. But in this neurogenic disorder, the urethral sphincter muscle, instead of relaxing completely during voiding, dyssynergically contracts causing the flow to be interrupted and the bladder pressure to rise.

Neurogenic bladder dysfunction, often called by the shortened term neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladder depending on the underlying cause and the symptoms. Symptoms include overactive bladder, urinary urgency, frequency, incontinence or difficulty passing urine. A range of diseases or conditions can cause neurogenic bladder including spinal cord injury, multiple sclerosis, stroke, brain injury, spina bifida, peripheral nerve damage, Parkinson's disease, or other neurodegenerative diseases. Neurogenic bladder can be diagnosed through a history and physical as well as imaging and more specialized testing. In addition to symptomatic treatment, treatment depends on the nature of the underlying disease and can be managed with behavioral changes, medications, surgeries, or other procedures. The symptoms of neurogenic bladder, especially incontinence, can severely degrade a person's quality of life.

A sacral anterior root stimulator is an implantable medical device enabling patients with a spinal cord lesion to empty their bladders.

<span class="mw-page-title-main">Urethral sphincters</span> Muscles keeping urine in the bladder

The urethral sphincters are two muscles used to control the exit of urine in the urinary bladder through the urethra. The two muscles are either the male or female external urethral sphincter and the internal urethral sphincter. When either of these muscles contracts, the urethra is sealed shut.

<span class="mw-page-title-main">Internal urethral sphincter</span> Urethral sphincter muscle which constricts the internal urethral orifice

The internal urethral sphincter is a urethral sphincter muscle which constricts the internal urethral orifice. It is located at the junction of the urethra with the urinary bladder and is continuous with the detrusor muscle, but anatomically and functionally fully independent from it. It is composed of smooth muscle, so it is under the control of the autonomic nervous system, specifically the sympathetic nervous system.

Sacral nerve stimulation, also termed sacral neuromodulation, is a type of medical electrical stimulation therapy.

<span class="mw-page-title-main">External sphincter muscle of female urethra</span>

The external sphincter muscle of female urethra is a muscle which controls urination in females. The muscle fibers arise on either side from the margin of the inferior ramus of the pubis. They are directed across the pubic arch in front of the urethra, and pass around it to blend with the muscular fibers of the opposite side, between the urethra and vagina.

<span class="mw-page-title-main">Spinal cord</span> Long, tubular central nervous system structure in the vertebral column

The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal cord is hollow and contains a structure called central canal, which contains cerebrospinal fluid. The spinal cord is also covered by meninges and enclosed by the neural arches. Together, the brain and spinal cord make up the central nervous system.

The pontine micturition center is a collection of neuronal cell bodies located in the rostral pons in the brainstem involved in the supraspinal regulation of micturition. When activated, the PMC relaxes the urethral sphincter allowing for micturition to occur. The PMC coordinates with other brain centers, including the medial frontal cortex, insular cortex, hypothalamus and periaqueductal gray (PAG). The PAG acts as a relay station for ascending bladder information from the spinal cord and incoming signals from higher brain areas.

<span class="mw-page-title-main">Overflow incontinence</span> Medical condition

Overflow incontinence is a concept of urinary incontinence, characterized by the involuntary release of urine from an overfull urinary bladder, often in the absence of any urge to urinate. This condition occurs in people who have a blockage of the bladder outlet, or when the muscle that expels urine from the bladder is too weak to empty the bladder normally. Overflow incontinence may also be a side effect of certain medications.

Dyssynergia is any disturbance of muscular coordination, resulting in uncoordinated and abrupt movements. This is also an aspect of ataxia. It is typical for dyssynergic patients to split a movement into several smaller movements. Types of dyssynergia include Ramsay Hunt syndrome type 1, bladder sphincter dyssynergia, and anal sphincter dyssynergia.

<span class="mw-page-title-main">Lumbar anterior root stimulator</span> Neuroprosthesis

A lumbar anterior root stimulator is a type of neuroprosthesis used in patients with a spinal cord injury or to treat some forms of chronic spinal pain. More specifically, the root stimulator can be used in patients who have lost proper bowel function due to damaged neurons related to gastrointestinal control and potentially allow paraplegics to exercise otherwise paralyzed leg muscles.

<span class="mw-page-title-main">Neurogenic bowel dysfunction</span> Human disease involving inability to control defecation

Neurogenic bowel dysfunction (NBD) is the inability to control defecation due to a deterioration of or injury to the nervous system, resulting in faecal incontinence or constipation. It is common in people with spinal cord injury (SCI), multiple sclerosis (MS) or spina bifida.

References