Editing Normal Erectile Physiology (section)

== Neuroanatomy and Neurophysiology of Penile Erection ==

=== Spinal centers and peripheral pathways ===
* '''<span style="color:#ff0000">Neural pathways necessary for complete sexual function:</span>'''
** '''<span style="color:#ff0000">Autonomic</span>'''
*** '''<span style="color:#ff0000">Parasympathetic</span>'''
*** '''<span style="color:#ff0000">Sympathetic</span>'''
** '''<span style="color:#ff0000">Somatic (sensory and motor)</span>'''

==== Autonomic ====
* '''<span style="color:#ff0000">Parasympathetic</span> ('''lateral horns '''<span style="color:#ff0000">S2-S4</span>)'''
** '''<span style="color:#ff0000">Responsible for tumescence</span>''' '''(increasing rigidity)'''
** The parasympathetic preganglionic fibers pass in the pelvic splanchnic nerves to the inferior hypogastric plexus (also known as the pelvic plexus)
* '''<span style="color:#ff0000">Sympathetic</span> ('''lateral horns '''<span style="color:#ff0000">T10-L2</span>)[https://www.nature.com/articles/3901188]'''
** '''<span style="color:#ff0000">Responsible for detumescence</span>''' '''(decreasing rigidity)'''
** The lumbar sympathetics from the superior hypogastric plexus (in older texts, hypogastric plexus or presacral nerve) travel to the inferior hypogastric plexus via the hypogastric nerve
** The sympathetic postganglionic fibers pass in the sacral splanchnic nerves from the sympathetic chain to the inferior hypogastric plexus
* '''<span style="color:#ff0000">The sympathetic and parasympathetic nerves merge in the inferior hypogastric/pelvic plexus to form the paired cavernous nerves, which enter the corpora cavernosa and corpus spongiosum and innervate the penis</span>'''
** '''Clinical implication: nerve-sparing prostatectomy aims to avoid injury to the cavernous nerves.'''

==== Somatic ====
* '''<span style="color:#ff0000">Center of somatomotor penile innervation (also motorneurons for external urinary sphincter) is in S2-S4 spinal cord region and is called Onuf's nucleus</span>'''
* '''<span style="color:#ff0000">Onuf nucleus (S2-S4)</span>'''
** '''<span style="color:#ff0000">Nerve fibers from neurons in Onuf's nucleus travel in the sacral nerves to become the pudendal nerve (S2-S4).</span>'''
** '''<span style="color:#ff0000">Pudendal nerve</span>'''
*** '''<span style="color:#ff0000">A mixed nerve (both sensory and motor components)</span>'''
*** Throughout most of its path, the nerve is closely associated with the branches of the internal pudendal artery and vein.[https://www.ncbi.nlm.nih.gov/books/NBK554736/]
***'''<span style="color:#ff0000">Responsible for (3):</span>'''
***# '''<span style="color:#ff0000">Penile sensation</span>'''
***#* The nerve fibers from the sensory receptors in the '''penile skin, glans, and urethra and within the corpus cavernosum''' converge to form bundles of the dorsal nerve of the penis, which joins other nerves to become the pudendal nerve
***# '''<span style="color:#ff0000">Contraction of the ischiocavernosus muscle</span>'''
***#* '''Produces the rigid-erection phase'''
***# '''<span style="color:#ff0000">Contraction of the bulbocavernosus/bulbospongiosus muscles (and external urethral sphincter)</span>'''
***#*'''Rhythmic contraction and compression on the proximal corpus spongiosum helps expel semen'''
*** Enters the spinal cord via the S2-S4 roots to terminate on spinal neurons and interneurons in the central gray region of the lumbosacral segment. Activation of these sensory neurons sends messages of pain, temperature, and touch by means of spinothalamic and spinoreticular pathways to the thalamus and sensory cortex for sensory perception

=== Neurotransmitters ===

==== Nitric oxide ====
* '''<span style="color:#ff0000">Principal neurotransmitter mediating erection</span>'''
* '''<span style="color:#ff0000">Synthesized by nitric oxide synthase (NOS)</span>'''
** '''<span style="color:#ff0000">Nitric oxide synthase</span>'''
*** '''<span style="color:#ff0000">3 isoforms; all 3 have been identified in the corpus cavernosum:</span>'''
***# '''<span style="color:#ff0000">Neuronal nitric oxide synthase (</span><span style="color:#0000ff">n</span><span style="color:#ff0000">NOS) in the nitrergic nerves: responsible for the i</span><span style="color:#0000ff">NNN</span><span style="color:#ff0000">itiation</span>'''
***# '''<span style="color:#ff0000">Endothelial nitric oxide synthase (</span><span style="color:#0000ff">e</span><span style="color:#ff0000">NOS): contributes to the maint</span><span style="color:#0000ff">EEE<span style="color:#ff0000">nance of smooth muscle relaxation and erection</span>'''
***# '''<span style="color:#0000ff">i</span><span style="color:#ff0000">NOS</span>'''
* '''<span style="color:#ff0000">Released from (2):</span>'''
*# '''<span style="color:#ff0000">Non-adrenergic/non-cholinergic (NANC) neurotransmission from postganglionic parasympathetic stimulation [from the cavernous nerves]</span>'''
*# '''<span style="color:#ff0000">Endothelium</span>'''
* '''<span style="color:#ff0000">Stimulates production of cGMP from GMP</span>''' by activating guanylate cyclase in smooth muscle
**'''<span style="color:#ff0000">Increased cGMP results in smooth muscle relaxation</span>''' by activating cGMP-dependent protein kinases, which phosphorylate certain proteins and ion channels, resulting in:
**# Opening of the potassium channels and hyperpolarization
**# Sequestration of intracellular calcium by the endoplasmic reticulum
**# Inhibition of voltage-dependent calcium channels, blocking calcium influx
* '''<span style="color:#ff0000">The smooth muscle regains its tone when cGMP is degraded by phosphodiesterase</span>'''

===== '''<span style="color:#ff0000">Phosphodiesterase (PDE)</span>''' =====
* '''<span style="color:#ff0000">Enzyme that degrades cGMP to GMP</span>'''
*11 subtypes
** '''All subtypes, except PDE6 which is specifically expressed in photoreceptor cells, have been identified in the corpus cavernosum'''
** '''<span style="color:#ff0000">PDE5 is the principal PDE for the termination of cavernous cGMP signaling</span>'''

==== '''Others''' ====
*'''Neurotransmitters that promote sexual function: dopamine, acetylcholine, oxytocin, and serotonin (5-HT)'''
** '''Acetylcholine contributes indirectly to penile erection''' by presynaptic stimulation of NO release from endothelial cells and inhibition of adrenergic neurons which decreases the release of norepinephrine
* '''Norepinephrine is the principal neurotransmitter mediating flaccidity'''
** α-Adrenergic nerve fibers and receptors are present in cavernous trabeculae and surrounding the cavernous arteries.
* '''GABAb receptors inhibit erectile function'''
* '''Prostaglandin E1 is erectogenic''', intracavernous injection of PGE1 is one of the safest and most effective treatments for ED
* Sonic hedgehog has been identified in the penis; inhibition of SHH in adult rats leads to rapid atrophy and disorganization of the corpus cavernosum. SHH has been shown to stimulate the expression of vascular endothelial growth factor (VEGF) and NOS in the penis
* '''Cannabinoid CB1''' receptor activation '''inhibits''' '''sexual function''' by modulating the paraventricular oxytocinergic neurons, which mediate erection. Antagonism of CB1 receptors in the PVN of male rats induces penile erection