Editing Functional: Neural Control of Storage and Voiding (section)

== Neural control of the Lower Urinary Tract ==

* Nature Reviews Neuroscience article on the [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897743/ neural control of micturition]
** See [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897743/figure/F1/ Figure 1] for efferent innervation of urogenital tract
* '''<span style="color:#ff0000">Micturition involves innervation from (3):</span>'''
*# '''<span style="color:#ff0000">Parasympathetic nervous system via the pelvic (S2-S4) nerve</span>''' 
*# '''<span style="color:#ff0000">Sympathetic nervous system via the hypogastric (T11-L2) nerve</span>'''
*# '''<span style="color:#ff0000">Somatic nervous system via the pudendal (S2-S4) nerve</span>'''
** '''<span style="color:#ff0000">The pelvic, hypogastric, and pudendal nerve are mixed nerves and carry efferent and afferent innervation</span>'''

=== Efferent innervation ===

==== Autonomic nervous system ====
* '''<span style="color:#ff0000">Parasympathetic</span>'''
** '''Parasympathetic preganglionic neurons''' innervating the LUT are located in the lateral part of the sacral '''intermediate gray matter of the S2-S4 spinal cord in a region called the sacral parasympathetic nucleus'''
** Parasympathetic preganglionic neurons send axons through the ventral roots to peripheral ganglia, where they release the excitatory transmitter Ach.
** '''Parasympathetic postganglionic neurons are located in the detrusor wall layer as well as in the pelvic plexus'''
** '''Patients with cauda equina or pelvic plexus injury are neurologically decentralized but may not be completely denervated'''. Cauda equina injury allows possible afferent and efferent neuron interconnection at the level of the intramural ganglia.
** '''<span style="color:#ff0000">Activation contributes to voiding by (2):</span>'''
**# '''<span style="color:#ff0000">Excitation (contraction) of the bladder</span>'''
**# '''<span style="color:#ff0000">Inhibition (relaxation) of the urethra</span>''' [not the bladder base]
* '''<span style="color:#ff0000">Sympathetic</span>'''
** '''<span style="color:#ff0000">Arises from the T11-L2 level of the spinal cord</span>'''
*** Sympathetic outflow from the rostral (anterior) lumbar spinal cord provides a noradrenergic excitatory and inhibitory input to the bladder and urethra
*** '''The peripheral sympathetic pathways follow a complex route''' that pass through the sympathetic chain ganglia to the inferior mesenteric ganglia and '''then through the hypogastric nerves to the pelvic ganglia'''
** '''<span style="color:#ff0000">Activation contributes to urine storage by (3):</span>'''
**# '''<span style="color:#ff0000">Inhibition (relaxation) of the bladder</span>'''
**# '''<span style="color:#ff0000">Excitation (contraction) of the bladder base</span>'''
**# '''<span style="color:#ff0000">Excitation (contraction) of the urethra</span>'''
** '''Animal studies have shown that sympathetic postganglionic fibers release noradrenaline (NA) and contribute to bladder relaxation during storage (via stimulation of β-adrenergic receptors expressed in detrusor)'''

==== Somatic nervous system ====
* '''<span style="color:#ff0000">The pudendal nerve arises from the S2-S4 level of the spinal cord</span>'''
** '''<span style="color:#ff0000">The motorneurons of the EUS are located along the lateral border of the ventral horn, commonly referred to as the Onuf nucleus</span>'''
* '''<span style="color:#ff0000">Activation contributes to urine storage by (1):</span>'''
*# '''<span style="color:#ff0000">Excitation (contraction) of the EUS</span>'''

=== Afferent innervation ===
* '''<span style="color:#ff0000">Afferent input reaches the spinal cord from (3):</span>'''
*#'''<span style="color:#ff0000">Pelvic nerve (S2-S4)</span>'''
*#'''<span style="color:#ff0000">Hypogastric nerve (T11-L2)</span>'''
*#'''<span style="color:#ff0000">Pudendal nerve (S2-S4)</span>'''
* '''The primary afferent neurons of the pelvic and pudendal nerves are contained in sacral dorsal root ganglia, whereas afferent innervation in the hypogastric nerves arises in the''' rostral '''lumbar dorsal root ganglia.'''
** The central axons of the dorsal root ganglia neurons carry the sensory information from the LUT to second-order neurons in the spinal cord. These second-order neurons provide the basis for spinal reflexes and ascending pathways to higher brain regions involved in micturition, continence, and mediation of sensation.
* '''<span style="color:#ff0000">Pelvic nerve afferents</span>'''
** '''<span style="color:#ff0000">Most important afferent for initiating and maintaining normal micturition</span>'''
**'''Consist of myelinated (Aδ) and unmyelinated (C) axons'''
** '''Monitor the volume of the bladder and the amplitude of the bladder contraction'''
**'''<span style="color:#ff0000">Provides most of the afferent input from the bladder and urethra</span>'''
*'''<span style="color:#ff0000">Hypogastric nerve afferents</span>'''
**'''<span style="color:#ff0000">Provides some of afferent input from the bladder and urethra</span>'''
*'''<span style="color:#ff0000">Pudendal nerve afferents</span>'''
**'''<span style="color:#ff0000">Provides afferent input from the striated muscle of the sphincter and pelvic floor</span>''' 
* '''<span style="color:#ff0000">Bladder Afferent Properties</span>'''

{| class="wikitable"
!Fiber type
!Location
!Normal function
!Inflammation effect
|-
!Aδ (finely myelinated axons)
|Smooth muscle
|'''Sense bladder fullness''' (wall tension)
|Increase discharge at lower pressure threshold
|-
!C fiber (unmyelinated axons)
|Mucosa
|Respond to stretch (bladder volume sensors)
|Increase discharge at lower threshold
|-
!<span style="color:#ff0000">C fiber (unmyelinated axons)</span>
|Mucosa muscle
|'''<span style="color:#ff0000">Nociception</span>''' to overdistention; silent afferent
|Sensitive to irritants; become mechanosensitive and unmask new afferent pathway during inflammation
|}

* '''Decreased afferent sensitivity or excitability due to a number of conditions in addition to normal aging may be an important factor leading to impaired voiding;''' '''diabetes mellitus has been linked with impaired sensory function''' and increased residual urine

* '''Modulators of afferent sensitivity'''
** '''Nitric oxide (NO)'''
*** '''Major transmitter mediating relaxation/inhibition of the urethral smooth muscle during micturition'''
*** PDE5 terminates the action of NO, and PDE inhibitors can be used therapeutically to prolong the action of NO at a number of sites including the bladder, prostate, and blood vessels
*** '''Influences bladder afferent nerve activity'''
**** '''Data suggest that these agents may represent a target for treatment of hypersensitivity disorders of the bladder such as BPS/IC and OAB.'''
** '''Urothelium releases ATP in response to stretch''' and this acts in a paracrine fashion to influence the function of myofibroblasts and bladder afferent nerves.
** A number of different members of the transient receptor potential channel family are expressed in the bladder, mostly in association with sensory nerve fibers involved in mechanotransduction and in nociception.
** '''Unmyelinated C fibers signal inflammatory or noxious events in the bladder; during inflammation and possibly other pathologic conditions, there is recruitment of mechanosensitive C fibers that form a new functional afferent pathway. This is the rationale for intravesical C-fiber neurotoxin capsaicin and RTX therapy'''
** Cannabinoid receptors in the bladder may have a modulatory role in sensory afferent signaling.