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

=== 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.