Neural Control of Micturition

1. NEURAL CONTROL OF
MICTURITION

2. INTRODUCTION
• Two main functions of LUT - storage and periodic elimination of urine
• Two functional units in the LUT:
• Reservoir - urinary bladder
• Outlet - bladder neck, urethra, urethral sphincter
• Coordination between these organs - mediated by a complex neural
control system located in the brain, spinal cord, and peripheral
ganglia

3. PERIPHERAL NERVOUS SYSTEM -
Efferent innervation
• Bilateral efferent innervation from the thoracic and lumbosacral
segments of the spinal cord
• Three sets of peripheral nerves:
• Sympathetic innervation - thoracolumbar outflow of the spinal cord -
hypogastric nerves and sympathetic chain
• Parasympathetic and somatic innervation originates in the sacral
segments of the spinal cord
• sacral parasympathetic - pelvic nerves
• sacral somatic nerves - primarily the pudendal nerves

4. • Preganglionic axons carrying information from the spinal cord to the
bladder synapse with autonomic ganglion cells widely distributed:
• Pelvic plexus
• Prevertebral sympathetic ganglia (inferior mesenteric ganglia)
• Paravertebral sympathetic chain ganglia
• Ganglia on the serosal surface and in the wall (intramural ganglia) of
the organs

5. Efferent pathways of the lower urinary
tract

6. SYMPATHETIC POSTGANGLIONIC
NERVES
• Sympathetic preganglionic pathways –
• Arise from the T11–L2 spinal segments
• Pass to the paravertebral sympathetic chain ganglia and then to
prevertebral ganglia in the inferior mesenteric, superior hypogastric
and pelvic plexus
• Postganglionic fibers travel through the hypogastric and pelvic nerves

7. • Sympathetic postganglionic nerves release NA
• Inhibitory input to smooth muscle in the body of the bladder
• β adrenergic inhibitory receptors in the detrusor muscle to relax the‑
bladder
• Excitatory input to smooth muscle of the urethra and bladder base
• α adrenergic excitatory receptors in the urethra and the bladder neck‑

8. PARASYMPATHETIC
POSTGANGLIONIC NERVES
• Sacral parasympathetic outflow
• Through the pelvic nerves
• Provides the major excitatory input to the urinary bladder
• Preganglionic neurons - located in the intermediolateral region of the
S2, S3, and S4 sacral spinal cord segments
• Axons pass through the pelvic nerves, synapse at ganglia in the pelvic
plexus and wall of the bladder

9. • Parasympathetic postganglionic nerves release both cholinergic (ACh)
and non-adrenergic, non-cholinergic transmitters
• Cholinergic transmission - M3 muscarinic receptors - detrusor
contraction and consequent urinary flow
• Non-cholinergic excitatory transmission - ATP actions on P2X
purinergic receptors in the detrusor muscle
• Parasympathetic input to the urethra induces relaxation during
voiding
• mediated by nitric oxide (NO)

10. SACRAL SOMATIC NERVES
• Somatic cholinergic motor nerves
• Arise in S2–S4 motor neurons in Onuf’s nucleus
• Reach the periphery through the pudendal nerves
• Supply the striated muscles of the external urethral sphincter (EUS)
(i.e., rhabdosphincter)

11. Afferent pathways
• Three sets of nerves carry afferent axons
• Sensations of bladder fullness are conveyed to the spinal cord by the
pelvic and hypogastric nerves
• Sensory input from the bladder neck and the urethra is carried in the
pudendal and hypogastric nerves
• consist of A delta (thinly myelinated) and C (unmyelinated) fibers

12. • A delta fibres - located within the detrusor muscle
• Respond to passive distention - known as “tension receptors”
• C fibers - dispersed more widely in the detrusor and suburothelium
• Insensitive to physiological filling - “silent” fibers
• Respond to noxious stimuli, provide nociception, and are sensitive to
changes in temperature and pH
• Thought to be important in the pathogenesis of urgency and the
Overactive Bladder (OAB)

13. • Cell bodies of these nerves - found in the dorsal root ganglia (DRG) of
the S2–S4 and T11–L2 dorsal roots
• Axons enter the dorsal horn, where they may
• Synapse with interneurons and either transmit impulses to higher
brain centers
• Synapse with neurons involved in spinal reflexes
• Thought to lie in the lateral part of the lateral column

14. GROSS ANATOMY OF THE LOWER
URINARY TRACT
• Bladder can be divided into two parts:
• Body - lies above the ureteral orifices
• Base - consists of the trigone and bladder neck
• detrusor muscle - smooth muscle with fibers arranged in spiral,
longitudinal, and circular bundles around the hollow viscus
• Bladder outlet - composed of the bladder base, urethra, and striated
urethral sphincter (i.e., rhabdosphincter)
• external urethral sphincter - striated muscle at the level of the
membranous urethra and is under voluntary control
• Internal urethral sphincter - extension of the smooth muscle fibers of the
detrusor muscle and is not under voluntary control

15. Anatomy of the bladder and its outlet.

16. THE NEUROLOGICAL CONTROL
OF THE BLADDER
• Micturition is under voluntary control, and is a learned process
• Develops with the maturing nervous system
• Neural pathways - organized as simple on–off switching circuits
• Maintain a reciprocal relationship between the urinary bladder and
urethral outlet
• Maintains the bladder and sphincter in the storage mode for
approximately 99.8% of life
• Switches to the voiding mode when socially appropriate

17. Storage phase
• Bladder functions as a reservoir, storing urine and providing
continence
• achieved by inhibition of parasympathetic activity
• active process of relaxation of the detrusor resulting in “bladder
compliance
• intravesical pressure is maintained below 10 cmH2O
• sympathetic and pudendal-mediated tonic contraction of the
sphincters ensures urinary continence

18. Sympathetic storage reflex -
Vesicosympathetic reflex
• Sympathetic reflex activity
• triggered by vesical afferent activity in the pelvic nerves
• Stimulates the sympathetic outflow to the bladder outlet and the
pudendal outflow to the external urethral sphincter
• Inhibits contraction of the detrusor muscle
• NA - inhibitory β-adrenergic receptors on the bladder body and
excitatory α-adrenergic receptors on the urethral sphincter and
bladder neck
• Enhances urine storage and suppresses voiding

19. Urine storage reflexes

20. Voiding phase
• Storage phase - can be switched to the voiding phase either
involuntarily or voluntarily
• First event is relaxation of the pelvic floor muscles and external and
internal urethral sphincters
• Achieved by inhibition of pudendal and sympathetic activity
• Followed by parasympathetic mediated detrusor contraction
• Coordinated activity between the detrusor and urethral sphincters
• Subject to modulatory influences of higher function

21. Voiding responses

22. Model of CNS Lower Urinary
Tract Control
• Switch of LUT function between storage and voiding
• Mediated by a long-loop spino-bulbo-spinal voiding reflex
• Forebrain circuits modulate this reflex
• Brainstem contains two principal nuclei concerned with voiding
• PAG and PMC [“M region” or “Barrington’s nucleus”]
• Storage - PAG is activated and PMC is inactive
• Voiding - Enhanced PAG activity and PMC activation
• L-region / pontine urine storage centre - excitation of this region -
tighten the urethral sphincter

23. Voiding reflexes

24. • Ascending afferent input from the spinal cord pass through PAG
before reaching the PMC
• Efferents from the PMC - project to
• Parasympathetic motor neurons of the detrusor in the sacral cord
• Inhibitory interneuronal activity - suppression of activity of
sympathetic and motor neurons in Onuf’s nucleus
• Reciprocal synergistic contraction of the detrusor muscle and
relaxation of the sphincter

25. Forebrain neural circuits involved in
human
voiding
• Normal adults - can postpone or hasten the micturition
• Ensure urination occurs only if it is consciously desired, emotionally
safe and socially appropriate
• PAG – projects to many parts of the forebrain, receives ascending
afferent activity from the bladder, and sends efferent signals back to
the bladder and urethra
• PAG - occupies a pivotal location between brain and bladder - so as to
suppress or enhance storage or voiding

26. Forebrain Regulation Of Micturition
• Decision to void or to postpone voiding
• Depends on forebrain processing of signals transmitted by bladder
afferents
• together with information from other organ systems
• circumstances that might influence the desirability of voiding
• Altering the input to the PAG - manipulate the strength of its
activation
• If activation of the PAG increases and approaches the set level, the
switch to voiding is advanced, and vice versa

27. A simple working model of the lower
urinary tract control system

28. Circuit 1
• Is voiding socially appropriate?
• Social aspects are primarily dealt with in the prefrontal cortex,
especially the medial prefrontal cortex (mPFC)
• Voiding can be initiated voluntarily by exciting the mPFC - inflow into
the PAG increases
• Voiding can be suppressed by deactivating the mPFC – reduces inflow
into the PAG
• mPFC can either delay or advance voiding by reducing (deactivating)
or increasing (activating) the flow of excitation along the pathway
from the mPFC to PAG

29. Circuit 2
• Is voluntary voiding emotionally appropriate?
• This limbic circuit includes the dorsalACC and the nearby SMA.
• It probably includes the anterior insula also (previously assigned to
circuit 1)
• activation of insula and dACC/SMA
• evokes strong desire to void or urgency
• sympathetic motor output to the LUT

30. Circuit 3
• Is voiding safe?
• This subcortical circuit includes the parahippocampal complex as well
as the PAG and probably the hypothalamus
• deactivation of parahippocampal regions tends to suppress voiding at
the PAG
• Hypothalamus might be part of this subcortical circuit, sending a
‘safe’ or ‘unsafe’ signal to the pontine micturition centre

31. • PAG activation
• driven by afferent input from the sacral spinal cord
• inhibitory or excitatory inputs from circuits one, two and three
• Voiding reflex is triggered if PAG activity reaches a certain set level
• PAG then activates the PMC

33. References
• de Groat, W. C., Griffiths, D. & Yoshimura, N. Neural control of
the lower urinary tract. Compr. Physiol. 5, 327–396 (2015)
• Griffiths D. Neural control of micturition in humans: a working
model. Nat Rev Urol. 2015 Dec;12(12):695-705
• de Groat WC, Yoshimura N. Anatomy and physiology of the
lower urinary tract. Handb Clin Neurol 2015;130:61-108