Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Innervation of the vagina and vulva

Richard F Hoyt Jr


The innervation of the female perineum and lower reproductive tract is clinically important in many respects. At one level, appreciation of the gross anatomy of peripheral neural pathways in the pelvis and perineum is the sine qua non of nerve-sparing operations designed to minimize disruptions in rectal, bladder, and sexual functions. At another, knowledge of the distribution and function of various nerve fiber types is essential to understanding the physiology and pathophysiology of genital arousal, sexual pleasure, and orgasm. It is therefore surprising that thorough descriptions of the innervation are so difficult to find. In most traditional accounts, the anatomy of the intrapelvic and pudendal nerves in the female is mentioned cursorily as being similar (although smaller in scale) to that in the male, which usually is treated in detail1-4 (see Chapters 5.3, 5.6, and 16.6 of this volume). More accurate accounts are, however, available in the surgical literature, and a number of recent studies have added significantly to our understanding. The goal of this chapter is to provide a systematic description drawn from a wide variety of sources. With the exception of one or two instances, clearly indicated, attention has been focused throughout on human female anatomy.

Basic plan of innervation

Elements of the nervous system

Innervation of the vulva, vagina, and related structures involves motor and sensory aspects of the somatic and visceral nervous systems (see Chapters 4.1 and 4.3 of this volume).

Somatic motor outflow is directed to voluntary, striated, skeletal muscle. At spinal levels, it arises in the ventral gray matter. Multipolar alpha-motor neurons send their axons out of the cord through the ventral roots, to be distributed in the dorsal and ventral primary rami of the spinal nerves.

Somatic sensory nerve cell bodies lie in the dorsal root ganglia of the spinal nerves. There are no synapses in dorsal root ganglia. Each unipolar, primary sensory neuron sends a peripheral process out through a spinal nerve to contact a sensory receptor or end in sensory terminals. It also extends a central process inward via the dorsal root toward the dorsal horn of the spinal gray matter. Somatic sensation can be subdivided into two broad categories: exteroception includes thermal, tactile, and pain (nociceptive) sensations from skin and the subcutaneous and deeper somatic tissues; proprioception involves the monitoring of stretch, contraction, acceleration, and deceleration in striated muscles, tendons, and joints.

Visceral motor pathways are directed toward cardiac muscle, smooth muscle, vessels, and glands. They require two neurons to convey a signal from the central nervous system to the tissues. These are arranged in series. A preganglionic cell in the brain or spinal cord sends its preganglionic axon into the periphery, where it synapses upon a ganglion cell. The ganglion cell then sends its postganglionic axon on to the target. Visceral motor outflow is subdivided into sympathetic and parasympathetic systems.

• Sympathetic motor pathways begin with multipolar preganglionic neurons located in the ventrolateral cell column of the spinal cord, from the first thoracic (T1) through the second lumbar (L2) segmental levels. These cells send their preganglionic axons out through the ventral roots and into the ventral rami of the T1-L2 spinal nerves. The preganglionic fibers leave each nerve as a “white” communicating ramus by which they enter the sympathetic trunk, an interconnected chain of sympathetic motor ganglia lying alongside the vertebral column from the base of the skull to the coccyx. Many preganglionic fibers end by synapsing in the chain. The ventral ramus of every spinal nerve receives a “gray” communicating ramus, a small bundle of postganglionic axons from ganglion cells in the sympathetic trunk. These fibers run in the spinal nerves and their branches to reach sweat glands, erector pili muscles, and the blood vessels in subcutaneous and deeper musculoskeletal tissues.

A substantial number of preganglionic axons pass through the sympathetic trunk without synapsing. Instead they travel in splanchnic nerves to end on prevertebral (preaortic) ganglion cells embedded in an interconnected series of visceral nerve plexuses extending along the aorta and internal iliac arteries. Postganglionic sympathetic fibers are distributed by subsidiary plexuses to reach smooth muscle, blood vessels, and glands in the abdominal and pelvic organs.

• Parasympathetic motor pathways begin in brainstem nuclei of certain cranial nerves, including the vagus, and in the ventrolateral cell column of the second, third, and fourth sacral (S2-4) spinal cord segments. Preganglionic axons leave the sacral cord via the ventral roots and emerge from the anterior sacral foramina in the ventral rami of the corresponding spinal nerves. They leave the rami through the pelvic splanchnic nerves and enter the pelvic visceral nerve plexus from which they are distributed to ganglion cells in or near the organs. Postganglionic fibers then innervate smooth muscle, certain blood vessels, and glands in the viscera.

Visceral sensory pathways return information from the organs. This input is termed interoception and includes pain (nociception), stretch reception, chemoreception, and baroreception. Sensory fibers retrace both sympathetic and parasympathetic outflow pathways. Therefore, visceral afferents enter the T1-L(sympathetic) and S2-4 (parasympathetic) cord segments and the brainstem (parasympathetic). As a rule, pain fibers follow the sympathetic pathway, and most other fibers follow the parasympathetic pathway. In the case of the vulva and the vagina, however, all visceral sensory input passes back along the parasympathetic route through the pelvic plexus and pelvic splanchnic nerves to reach the sacral spinal cord.

Distribution of the neural elements in the vulva and vagina

As summarized in Fig. 4.2.1, skin and subcutaneous tissues of the female perineum are innervated by somatic sensory fibers distributed through branches of the lumbar, sacral, and coccygeal plexuses, all formed by ventral primary rami of spinal nerves. This same distribution includes the lower 2-3 cm of the vagina.

Voluntary striated muscles of the perineum and pelvic floor, including the external urethral and anal sphincters, are innervated by somatic motor and sensory (proprioceptive) fibers of the sacral plexus, either through branches of the pudendal nerve or through branches traveling on the upper surface of the pelvic floor.

Smooth muscle, vessels, and glands in the vagina, cervix, bladder neck, and urethra receive sympathetic and parasympathetic motor innervation through the interconnected pelvic, uterovaginal, and vaginal visceral nerve plexuses (Fig. 4.2.2). This includes the erectile tissues of the clitoris and bulbs of the vestibule.

Figure 4.2.1. General distribution of cutaneous nerves to the female perineum. Reproduced with permission from Hollinshead2 (Fig. 16-2, p 822).

Visceral sensation, including pain, returns from these same organs along the parasympathetic pathway, through the intrapelvic visceral nerve plexuses and pelvic splanchnic nerves, to reach the S2-4 segments of the spinal cord.

Pathways of innervation

Somatic pathways

• Ilioinguinal nerve. The ilioinguinal is a mixed motor and sensory somatic nerve. It arises from the L1 ventral primary ramus, passes laterally and downward posterior to the psoas major muscle and behind the parietal fascia on the quadra- tus lumborum, and iliacus muscles. The nerve then pursues a circumferential course through the anterior abdominal wall, which it supplies. The terminal portion of the nerve emerges through the external inguinal ring below the round ligament of the uterus, accompanies the ligament downward in front of the pubis, and ends by supplying sensory innervation to skin over the mons pubis and portions of the labium majus, labium minus, and vestibule anterior to the urethral orifice.

Figure 4.2.2. The pelvic visceral nerve plexus in the human female. Reproduced with permission from Hollinshead2 (Fig. 15-36, p 805).

• Genitofemoral nerve. The genitofemoral is a somatic sensory nerve formed behind psoas major by contributions from the L1 and L2 ventral primary rami. Descending obliquely, it emerges onto the anterior surface of the muscle. As it continues its downward course, the nerve lies behind the parietal fascia covering psoas and divides at a highly variable point into its femoral and genital branches. The femoral branch passes behind the inguinal ligament lateral to the femoral artery to reach skin of the femoral triangle. The genital branch crosses in front of the external iliac artery, enters the inguinal canal through its deep ring, traverses the canal, and reaches skin over anterior portions of the vulva, overlapping the distribution of the ilioinguinal nerve.

 Sacral plexus. Virtually all striated muscles of the perineum and perineal skin behind the urethral orifice are innervated by branches of the sacral plexus, which is formed from lower lumbar and sacral ventral primary rami in front of the sacrum, behind the parietal fascia covering the piriformis and coccygeus muscles.

Fibers from L4 and L5 unite to form the lumbosacral trunk, which descends behind the medial portion of psoas major, between the muscle and the sacral promontory. Having crossed the pelvic brim, the trunk joins the Sventral ramus shortly after it emerges through the first anterior sacral foramen. Together, these fibers pass downward and laterally to join the S2-4 ventral rami, all of which exit their respective anterior sacral foramina and converge laterally on the greater sciatic foramen. Extrapelvic branches of the sacral plexus exit the pelvic cavity through the greater sciatic foramen and appear in the gluteal region. The superior gluteal nerve leaves above the piriformis muscle; the pudendal, inferior gluteal, and sciatic nerves leave below piriformis, as do the posterior cutaneous nerve of the thigh and the nerves to quadratus femoris and obturator internus muscles.

Deep to the lower part of the gluteus maximus muscle, the posterior cutaneous nerve of the thigh (S1-3) gives rise to its perineal branch, which turns forward below the ischial tuberosity. This nerve runs anteriorly across the hamstring muscles and parallel to the ischiopubic ramus to supply sensory innervation to the lateral aspect of the labium majus.

The S4 ventral ramus sends a perineal branch through coccygeus or between the coccygeus and levator ani muscles into the ischioanal fossa, where it supplies the posterior part of the external anal sphincter and a small area of skin behind the anal opening. A descending branch from this same ventral ramus joins with the small ventral rami of the 5 th sacral and the coccygeal spinal nerves to form a delicate coccygeal plexus on the pelvic surface of the coccygeus muscle. From this plexus, small anococcygeal nerves pass posteriorly through coccygeus and around the lateral margin of the coccyx. They pierce the sacrotuberous ligament and are distributed to skin behind the anal opening and overlying the coccyx.

The sacral plexus also provides branches directly to striated muscles of the pelvic floor. One of these, from the Sventral ramus, enters the pelvic surface of coccygeus. Others, more variable in composition, arise from the Sand/or S4 rami and run forward on the pelvic surface of levator ani. These usually supply the posterior portion of the muscle, principally iliococcygeus, but some fibers may descend through the pelvic floor to end in the external urethral sphincter.

• Pudendal nerve. The pudendal nerve is the principal somatic motor and sensory nerve of the perineum. Formed primarily from the 3rd sacral spinal nerve, with lesser contributions from S2 and S4, it pursues a short intrapelvic course before passing outward below piriformis with the internal pudendal vessels. The pudendal nerve is the most medial of the neurovascular elements emerging through the greater sciatic foramen. It appears only briefly in the gluteal region, grooving the posterior surface of the ischial spine or the sacrospinous ligament before passing deep to the sacro- tuberous ligament and into the perineum. The nerve runs forward against the lateral wall of the ischioanal fossa in the pudendal (Alcock’s) canal, a fascial sleeve tethered loosely to the free (medial) surface of the obturator internus muscle. Soon after entering the canal, the pudendal nerve gives off its inferior rectal (inferior hemorrhoidal) branch; shortly thereafter, it ends by dividing into the perineal nerve and the dorsal nerve of the clitoris.

О Inferior rectal nerve. Soon after entering Alcock’s canal the pudendal nerve gives off its inferior rectal branch. This leaves the canal through its medial wall and crosses the ischioanal fossa toward the anus. As it does so, it supplies the posterior two-thirds of the external anal sphincter and distributes numerous sensory branches to the lower portion of the anal canal and to skin behind and lateral to the anal opening. Shafik and Doss5 have described this pattern in some detail. These authors also noted the existence of a discrete labial branch and a motor branch to levator ani; most sources attribute extrapelvic innervation of the levator to perineal branches of the pudendal nerve and 4th sacral ventral ramus and simply mention communications among the three nerves in the ischioanal fossa.

О Perineal nerve. One of two terminal branches of the pudendal nerve, the perineal nerve leaves the distal end of Alcock’s canal, directed anteriorly and medially. Again, reports vary, but the general picture is clear. As it approaches the rear edge of the perineal membrane, the nerve gives rise to deep and superficial sets of branches. The medial branches are directed primarily to striated musculature, including the anterior portion of the external anal sphincter, transverse perineal, ischiocavernosus, bulbospongiousus, and levator ani muscles, as well as the external (voluntary) urethral sphincter. The remaining, superficial, branches of the perineal nerve are almost exclusively cutaneous; they form the lateral and medial posterior labial nerves. The lateral set communicates with the perineal branch of the posterior cutaneous nerve of the thigh to supply the lateral margin of the perineum; the medial set runs forward to reach the labia majora and minora, the vestibule, and skin anterior to the anal opening. Somatic sensory innervation to the lower 2-3 cm of the vagina is most likely provided by the medial posterior labial and the inferior rectal nerves.О Dorsal nerve of the clitoris. This, like the perineal nerve, leaves the distal end of Alcock’s canal. It is projected forward and medially through the anterior recess of the ischioanal fossa, running against the margin of the ischiopubic ramus and on the upper surface of the perineal membrane, through which it sends a branch to the corpus cavernosum. Descending through the perineal membrane, it lies between the crus clitoris and the pubic ramus, then crosses medially above the crus, penetrates the suspensory ligament, and gains the dorsum of the clitoral body. Here, at the “hilum” of the clitoris, the dorsal nerve receives an important contribution from the cavernous nerve extending downward along the urethra from the intrapelvic uterovaginal visceral plexus (see below).6 It then runs distally between the deep fascia and tunica albuginea, separated from the midline by the dorsal artery of the clitoris, giving off branches that spread laterally onto the sides of the corpus. Most are destined for skin of the clitoris and prepuce, but small branches enter the lateral aspect of the tunica albuginea. The dorsal nerve ends in a leash of branches to the glans, especially its dorsal surface.

Visceral pathways

Perineal blood vessels and the sweat glands and erector pili muscles of the skin all receive a postganglionic sympathetic motor innervation. This outflow pathway begins with preganglionic neurons in the L1-2 spinal cord segments, whose fibers pass through white communicating rami to synapse on ganglion cells in lumbar and sacral portions of the sympathetic chain. Postganglionic axons traverse gray communicating rami to reach lumbar and sacral spinal nerves and are distributed to the perineum by branches of the ilioinguinal, genitofemoral, posterior femoral cutaneous, and pudendal nerves (Fig. 4.2.1).

The upper vagina, cervix, urethra, greater vestibular glands, and erectile tissues of the clitoris and vestibular bulbs receive sympathetic motor, parasympathetic motor, and visceral sensory innervation. The sympathetic outflow pathway originates in the T11-L1 spinal cord segments. Preganglionic fibers pass into the sympathetic chain via white communicating rami. Most leave the chain through lumbar splanchnic nerves to enter the interconnected system of visceral nerve plexuses that lie around the abdominal aorta and between the common iliac vessels. Sympathetic fibers continue their descent through the hypogastric nerves on the anterior surface of the sacrum and onto the pelvic floor, where they enter the inferior hypogastric (pelvic) plexus. Here they join preganglionic parasympathetic fibers, which arise in the S2-4 cord segments and enter the plexus through pelvic splanchnic nerves from the corresponding ventral primary rami. Intermingled sympathetic and parasympathetic fibers pass through the uterovaginal plexus along the uterine artery to reach the cervix; others turn downward with the vaginal artery, supplying both the vagina and the urethra; and still others continue their descent through the “cavernous nerves” alongside the vagina and urethra to end in the clitoris, bulb of the vestibule, and greater vestibular glands. Sympathetic ganglion cells are scattered along the route. Some lie in the sympathetic chain, but most are located in the pelvic and uterovaginal plexuses. Parasympathetic ganglion cells occur in distal reaches of the uterovaginal plexus and in the vaginal adventitia. Visceral afferent nerves sensing pressure, distention, and pain retrace the paths taken by parasympathetic motor outflow to the region. They enter the 2nd, 3rd, and 4th sacral cord segments, which also receive somatic sensory information from the vulva and perineum through branches of the pudendal nerve. Their cell bodies lie in dorsal root ganglia of the corresponding spinal nerves.

Detailed knowledge of the visceral neural pathways is clinically important not only because elements of the system can be affected by a wide variety of disease processes, but also because they can be damaged by surgical procedures within the female pelvis.

 Sympathetic trunk. On each side, the sympathetic trunk enters the abdomen from the thorax by passing behind the medial arcuate ligament on the anterior surface of the psoas major muscle. Lying in the extraperitoneal connective tissue, it descends in front of the origin of psoas from the lumbar vertebral bodies and is overlapped either by the aorta (left side) or by the inferior vena cava (right side). The trunk crosses in front of the lumbar segmental vessels and then behind the common iliac artery and vein to gain the anterior surface of the sacrum. On the sacrum, it courses downward and toward the midline, passing medial to the first three anterior sacral foramina and their emerging S1-3 ventral primary rami. After skirting the lateral margin of the fourth anterior sacral foramen and its ventral ramus, the trunk ends independently or joins that of the opposite side in a small ganglion impar in front of the coccyx. Ganglionation is highly irregular in the lumbar region, but three or four sacral sympathetic ganglia usually can be identified. Along its course, the sympathetic trunk distributes postganglionic (gray) communicating rami to all lumbar and sacral spinal nerves, and sends four lumbar and two sacral splanchnic nerves into successively lower levels of the continuous abdominopelvic visceral nerve network (see below).

 Abdominopelvic visceral nerve plexuses. Organs in the abdominal and pelvic cavities receive their innervation through a longitudinal network of visceral nerve fibers extending from the aortic hiatus in the diaphragm downward onto the pelvic floor. This vertically disposed system lies in the extraperitoneal visceral connective tissue, internal to a plane formed by the aorta and the common and internal iliac arteries. It contains ganglia, microganglia, and isolated ganglion cells (largely if not exclusively sympathetic) embedded in an intermixture of preganglionic and postganglionic sympathetic fibers, preganglionic parasympathetic fibers, and a variety of visceral afferent fibers concerned with pain (nociception), stretch, and other information. Preganglionic sympathetic and accompanying visceral sensory fibers are provided through splanchnic nerves from thoracic, lumbar, and sacral portions of the sympathetic trunk; preganglionic parasympathetic and associated visceral sensory fibers are fed into the network from above, through branches of the vagus nerve, and from below, through pelvic splanchnic nerves from the S2-4 ventral rami.

Although the abdominopelvic visceral plexus forms a single continuous network, and should always be thought of as such, the central longitudinal system is usually described as a number of separate units. Beginning above, these are the celiac, intermesenteric (aortic), superior hypogastric, and inferior hypogastric (pelvic) plexuses, the last two being linked across the pelvic brim by the so-called hypogastric nerves. Their extensions pass outward along visceral branches of the aorta and internal iliac arteries to reach the organs. These subsidiary plexuses generally are named for the vessels they accompany or the organs they supply. For example, the pelvic plexus distributes its fibers to pelvic viscera through its major offshoots, the rectal, uterovaginal, and vesical plexuses.

● Celiac plexus. This is the uppermost - and largest - of the abdominal autonomic plexuses. It lies in front of the aorta just below the aortic hiatus, surrounding the origins of the celiac trunk and superior mesenteric artery. Large, irregular right and left celiac ganglia are embedded in the plexus, along with the superior mesenteric ganglion and smaller aggregates of sympathetic ganglion cells. On each side, a small aorticorenal ganglion lies in the plexus near the origin of the renal arteries. Sympathetic input to the plexus comes through the greater, lesser, and least splanchnic nerves carrying fibers from the T5-9 (greater), T10-11 (lesser), and T12 (least) spinal cord segments. These nerves issue from the thoracic sympathetic trunk and reach the plexus by passing through the crus of the diaphragm or behind the medial arcuate ligament. The plexus also receives fibers from lower thoracic and upper lumbar cord segments through the first lumbar splanchnic nerve. Parasympathetic motor fibers are added to the plexus by branches of the left and right vagus nerves, which have entered the abdomen along with the esophagus. Visceral sensory fibers in the celiac plexus follow both splanchnic and vagal routes.

● Intermesenteric plexus. The intermesenteric, or aortic, plexus extends downward from the celiac plexus as a series of interconnected strands in front of and alongside the aorta between the origins of the superior and inferior mesenteric arteries. Small, discrete sympathetic ganglia and ganglion cells are embedded in the meshwork of nerve fibers, and occasionally a larger, inferior mesenteric ganglion can be identified. The lower part of the intermesenteric plexus receives the second lumbar splanchnic nerve.

● Superior hypogastric plexus. The superior hypogastric plexus is a network of strands continued downward from the aortic plexus in front of the aortic bifurcation and between the right and left common iliac vessels onto the 5th lumbar vertebral body and the sacral promontory. It may contain scattered sympathetic ganglion cells and usually receives the 3rd and 4th lumbar splanchnic nerves. Few, if any, vagal fibers reach the superior hypogastric plexus.

● Hypogastric nerve. Arising from the superior hypogastric plexus in a variety of configurations, ranging from a single strand to a plexiform network, the left and right hypogastric nerves gradually diverge from one another as they descend on the anterior surface of the sacrum. Each nerve passes downward in the visceral pelvic fascia, at first roughly parallel with the ureter but some 2 cm dorsomedial to it. As it does so, it lies between the peritoneum and the lateral wall of the true pelvis, from which it is separated by the internal iliac vessels. In its course, the nerve runs lateral to the rectum and turns forward into the relatively loose connective tissue forming the base (lateral portion) of the crescentic uterosacral fold, whose acute medial margin bounds the rectouterine peritoneal pouch. Here, opposite the rectal ampulla, the hypogastric nerve expands into the pelvic plexus.

● Pelvic plexus. The inferior hypogastric, or pelvic, plexus (Fig. 4.2.2) is a densely woven network of nerve fibers studded with small ganglia and isolated ganglion cells. Most but not all of these are sympathetic in nature. The plexus is roughly 2.5-3.5 cm high and about 5 cm long. It is embedded in a reasonably discrete sheet of extraperitoneal connective tissue (pelvic visceral fascia) medial to the internal iliac vessels and their branches, and it extends anteromedially through the base of the cardinal ligament, directed toward the base of the bladder. Thus, although its origin from the hypogastric nerve is just external to the peritoneum covering the lateral pelvic wall, distal portions of the plexus are situated below the level of the peritoneum and close to the pelvic floor.

Most sympathetic motor fibers reach the pelvic plexus through the hypogastric nerve. This input is reinforced by two small sacral splanchnic nerves that arrive directly from the sacral sympathetic trunk. All preganglionic parasympathetic motor outflow into the plexus is carried in the pelvic splanchnic nerves. These leave the S2-4 ventral rami proximal to formation of the sacral (somatic) plexus, penetrate the parietal fascia covering piriformis, run anteromedially through the dorsal region of the parametrium in the base of the cardinal ligament, and enter the lateral surface of the pelvic plexus level with the 5th sacral vertebral segment. Visceral sensory fibers are provided by both hypogastric and pelvic splanchnic nerves.

● (Middle) rectal plexus. The rectal plexus consists of a variable series of strands leaving the posteroinferior margin of the pelvic plexus. They pass medially and downward to reach the posterolateral margin of the rectum through the visceral connective tissues forming the lateral ligament of the rectum (rectal “stalk” or “pillar”). The plexus does not usually accompany the middle rectal branch of the internal iliac artery, which reaches the rectal wall just above the pelvic floor and not through the lateral ligament.2,7 Thus, the frequently used term ‘middle rectal plexus’ is a misnomer.

● Vesical plexus. The vesical plexus represents the anteroinferior continuation of the pelvic plexus. It accompanies the inferior vesical branches of the internal iliac arterial system downward, medially, and forward in the visceral connective tissue forming the posterior portion of the pubocervical ligament. The plexus courses lateral to the cervix and the vaginal vault to supply the bladder, bladder neck, and proximal urethra.

● Uterovaginal plexus. The uterovaginal plexus leaves the medial aspect of the pelvic plexus in the base of the broad ligament and turns toward the midline, running with the uterine vessels in the upper portion of the cardinal ligament. The plexus contains numerous small ganglia, and occasionally a larger, “cervical” ganglion can be found. Nerve fibers are given off directly to the cervix; those to the body, fundus, and tube turn upward in the parametrial core of the broad ligament with the uterine vessels.

● Vaginal plexus. The intermixture of sympathetic, parasympathetic, and visceral sensory nerve fibers destined for the vagina, urethra, and vulva turn downward with the vaginal artery. Although accounts differ slightly, there is a general consensus that the plexus consists of a series of interlacing longitudinal strands descending at first on the lateral vaginal wall and then in the groove between the vagina and the urethra.10 Here they are said to occupy the 2 and 10 o’clock positions on the vaginal perimeter (12 o’clock being the ventral midline).6 Branches fan outward from these trunks to invest the vagina. Proximally, the density of innervation is greatest on the anterior wall, but, distally, it decreases as the connective tissue plane between vagina and urethra thins markedly. Parasympathetic ganglion cells are scattered sparsely along the course of larger nerves in the adventitia. Smaller bundles of nerve fibers penetrate the vaginal wall. These traverse the muscularis, supplying vascular and nonvascular smooth muscle, and form a rich plexus in the lamina propria.11,12 Rarely, fibers cross the basement lamina and ramify among cells of the stratified squamous vaginal epithelium.11

The vaginal plexus is closely associated with the vesical plexus (see above), and it distributes branches to the bladder neck and the proximal and middle portions of the urethra.6,9 Most of the latter hug the lateral margin of the urethra and penetrate the muscle coat anterolaterally, at the 1 and 11 o’clock positions.Motor fibers are destined for urethral smooth muscle, vessels, and glands while sensory fibers contribute to a plexus beneath the epithelium.

● Cavernous nerves. The cavernous nerves carry visceral innervation to the erectile tissues of the vulva. Arising as downward extensions of the vaginal plexus, they descend along the posterolateral border of the proximal urethra (5 and 7 o’clock positions).6 Gradually they incline forward onto the lateral urethral wall, upon which they pass through the perineal membrane. Below the membrane, each nerve distributes branches to the corresponding dorsal nerve of the clitoris and (presumably) to the bulb of the vestibule. The cavernous nerve ends by piercing the tunic albuginea of the corpus cav- ernosum just proximal to the body of the clitoris.


The functional significance of any neural pathway depends on the nature of the neurotransmitters produced and released by its fiber types (see Chapter 5.4 in this volume).

Acetylcholine has long been recognized as the basic motor neurotransmitter in the somatic nervous system, responsible for innervation of striated, voluntary muscle. Acetylcholine is the ganglionic neurotransmitter in both sympathetic and parasympathetic systems and is an important postganglionic agent in parasympathetic regulation of cardiac muscle, smooth muscle, vessels, and glands. It also serves as the sympathetic transmitter in sweat glands of the skin.

Noradrenaline, also known as norepinephrine, is the classic sympathetic postganglionic neurotransmitter in cardiac muscle, smooth muscle, blood vessels, and glands.

Nonadrenergic, noncholinergic neurotransmitters have been identified in substantial numbers during the past 50 years. They encompass a wide variety of molecules, including amino acids, amines, peptides, purines, and even nitric oxide, which, as a potent vasodilator, has been shown to play an important role in engorgement of the erectile tissues. Neuropeptides, such as calcitonin-gene-related peptide, substance P, and vasoactive intestinal polypeptide, are now recognized as important neurotransmitters in somatic and visceral sensory nerve fibers.

Various means have been used to study the distribution of neurotransmitters in tissues. Cholinergic fibers were identified initially by a histochemical reaction to localize activity of acetylcholinesterase, the enzyme responsible for degradation of acetylcholine released at nerve terminals. Adrenergic fibers were identified by a formaldehyde-induced amine fluorescence reaction that localized noradrenaline itself. Although still in use, these techniques are cumbersome: acetylcholinesterase reactions involve the use of highly toxic inhibitors to determine the specificity of the enzyme, and formaldehyde-induced fluorescence is best carried out in freeze-dried material. Work has, however, been greatly facilitated by the development of modern immunohistochemical methods, which permit two basic strategies. In the first, antibodies are developed that recognize specific neurotransmitter molecules such as calcitonin-gene-related peptide, substance P, vasoactive intestinal polypeptide, and neuropeptide Y. In the second approach, antibodies are used to localize key enzymes or other molecules involved in the metabolism of a given neurotransmitter. Examples include tyrosine hydroxylase for noradrenaline, choline-acetyl transferase and vesicular acetylcholine transporter for acetylcholine, and nitric oxide synthase for nitric oxide. In the latter case, two different enzymes can be identified, one in neurons (neural nitric oxide synthase) and the other in vascular endothelium (endothelial nitric oxide synthase). Although neurotransmitter localizations reveal only subpopulations of neurons along a pathway or in a tissue, antibodies to protein-gene product 9.5 (PGP 9.5)8'11'12 and to S-100 proteinserve as generic immunohistochemical markers for the entire population of nerve fibers and ganglion cells.

To date, a number of neurotransmitter systems have been demonstrated in nerves associated with the human female perineum and reproductive tract. These include the following:

 acetylcholine, shown by acetylcholinesterase13 and vesicular acetylcholine transporter6

 noradrenaline, shown by tyrosine hydroxylase14

 nitric oxide, shown by neural nitric oxide synthase6,11,15 and endothelial nitric oxide synthase15

 neuropeptide Y11'14'16-18

 substance P6,11,14

 calcitonin-gene-related peptide P6,11,14

 vasoactive intestinal polypeptide P.11,14,16

As summarized by Butler-Manuel et al.,14 vasoactive intestinal polypeptide often colocalizes with cholinergic markers and is therefore considered to be a neurotransmitter in the parasympathetic system along with acetylcholine. Neuropeptide Y, on the other hand, often colocalizes with tyrosine hydroxylase and is viewed with noradrenaline as a postganglionic sympathetic agent. Calcitonin-gene-related peptide is thought to be a sensory transmitter, and substance P is associated with nociception and sensorimotor functions. Presumably, the latter activity would involve axon reflexes. Vasoactive intestinal polypeptide is also classed as a sensory neurotransmitter.1

Recent immunohistochemical studies have begun to plot systematically the distribution of nerve fibers and neurotransmitters in human female genital tissues,6,11 but certain points must be considered in assessing the functional implications of any neurotransmitter localization, no matter how thorough. First, the fact that two neurotransmitters colocalize does not necessarily mean that they always will do so. Second, developmental plasticity may be a factor in evaluating results obtained in fetal material: considerable remodeling of the nervous system can occur between the second trimester of gestation and sexual maturity. Third, neurotransmitters are only part of the puzzle, for their actions depend on the spectrum of specific receptors available to them, and these may be distributed unevenly in target tissues. At present, significant gaps remain to be filled in our map of neurotransmitter distributions, little is known about the availability and especially the tissue localization of receptors for specific neurotransmitters, and the possibility that the hormonal status of women may affect the spectrum of neurotransmitters and their receptors is only now being acknowledged.

Targets of motor innervation

Skin of the perineum

Sweat glands and blood vessels in the perineal skin receive visceral, sympathetic innervation. Postganglionic fibers pass through gray rami from the sympathetic trunk to enter the ventral primary rami of lumbar, sacral, and coccygeal nerves. They are distributed to skin of the urogenital region and vulva by appropriate branches of the ilioinguinal, genitofemoral, pudendal, and lateral femoral cutaneous nerves (Fig. 4.2.1). Skin of the anal region is supplied through inferior rectal and perineal branches of the pudendal nerve and through the perineal branch of the S4 ventral ramus. Preganglionic outflow is from lower thoracic and upper lumbar cord segments. The postganglionic neurotransmitters are noradrenaline (blood vessels) and acetylcholine (sweat glands).

Striated, voluntary muscles of the perineum

All striated muscle fibers in the region receive a somatic motor innervation that utilizes acetylcholine as the neuromuscular transmitter. Bulbospongiosus, ischiocavernosus, and transversus perinei are supplied from the S2-4 spinal cord segments via the sacral plexus and the perineal branch of the pudendal nerve. The external (voluntary) anal sphincter is supplied by the same cord segments. Motor fibers travel in the inferior rectal and perineal branches of the pudendal nerve to reach the posterior two-thirds and the anterior one-third of the muscle, respectively. Most sources agree that the sphincter is also innervated by the perineal branch of the 4th sacral ventral ramus, which descends through the pelvic floor. This point is of surgical interest because it means that fecal continence can be impaired by dissections involving the upper (internal) surface of the pelvic floor as well as those conducted in the ischioanal fossa. Blood vessels in all these striated muscles receive an adrenergic innervation from the sympathetic trunk; postganglionic fibers are distributed through the appropriate branches of the sacral plexus.

Although the voluntary, external urethral sphincter is a perineal muscle, its nerve supply will be described with that of the urethra (see below).

Striated, voluntary muscles of the pelvic floor (see Chapters 12.3 and 17.4 of this volume)

The muscles of the pelvic diaphragm also receive cholinergic somatic motor innervation from the sacral spinal cord. This is distributed by branches of the sacral plexus that also carry adrenergic postganglionic sympathetic fibers to local blood vessels. The coccygeus is supplied on its pelvic surface by direct branches from the S3 and S4 ventral primary rami.2 Anterior portions of the muscle complex collectively termed “levator ani”, including pubovaginalis and puborectalis (see Chapter 4.4 of this volume), are innervated on their extrapelvic (perineal) surface by twigs from the perineal branch of the pudendal nerve (S2-4). Most sources agree on the existence of an intrapelvic pathway as well, but differ in the details. It has been described as an intrapelvic branch of the pudendal nerve,19 as a single nerve arising from the S3 or S4 ventral ramus,2 as separate twigs from the S3 and S4 rami,1-3 and even as the sole motor nerve to the entire levator complex. None of these patterns lie outside the range of normal variation: the author, for instance, can remember a dissection in which the dorsal nerve of the penis ran forward above the pelvic floor, distributing fine branches to levator ani along its course. The clinical implications are clear, however: motor innervation to the levator ani can be compromised during intrapelvic as well as perineal surgical procedures.

Cervix and vagina

Smooth muscle, vessels, and glands of the lower genital and urinary tracts all receive sympathetic and parasympathetic innervation through the pelvic, uterovaginal, and vaginal visceral nerve plexuses. Sympathetic input comes from the T11-Lspinal cord segments, through the superior hypogastric plexus and the hypogastric nerves; parasympathetic input is provided from the S2-4 cord segments through the pelvic splanchnic nerves. A wide variety of transmitters and transmitter markers have been localized to nerve fibers and/or ganglion cells in components of this network, including vesicular acetylcholine transporter,6 vasoactive intestinal polypeptide,14,16 neuropeptide Y,14,16 tyrosine hydroxylase,14 calcitonin-gene-related peptide,6,14 substance P,6,14 and neural nitric oxide synthase.6 However, as will become evident, there is at present no comprehensive picture of the distribution and actions of these transmitters in the target tissues.

Blood vessels in the cervix and vagina are innervated by nerve fibers containing acetylcholine,13 vasoactive intestinal polypeptide,13,16 neuropeptide Y,13,16,17 and noradrenaline. Those in the vagina also receive fibers immunoreactive for neural nitric oxide synthase and calcitonin-gene-related peptide.11 Physiologic studies in humans and rabbits17,18 have demonstrated that noradrenaline constricts the vessels, and vasoactive intestinal polypeptide relaxes them. Neuropeptide Y, a weak vasoconstrictor by itself, potentiates the effect of noradrenaline by inhibiting vasoactive intestinal polypeptide-induced vasodilation. Vaginal hemodynamics are of major importance because vaginal lubrication depends largely on transudation of fluid across the lining epithelium. The fact that many subepithelial capillaries are innervated is therefore of interest, and Hoyle et al.11 have suggested that neuropeptides may regulate capillary permeability. The vaginal plexus also contains many neural nitric oxide synthase-immunoreactive nerve fibers,6 and some of these find their way into the vaginal wall.11 Although their targets in the vagina are unclear at present, the vascular system is a likely possibility given that nitric oxide is a potent vasodilator in erectile tissue.15 The significance of calcitonin-gene-related peptide in regulation of vaginal blood flow is unknown.

Although the vagina itself is devoid of glands, secretory activity of cervical glands, which contribute to vaginal lubrication, is promoted by parasympathetic innervation.

Nerve fibers containing neuropeptide Y and vasoactive intestinal polypeptide have been described among fascicles of nonvascular smooth muscle in the cervix and vagina. These are indicative of innervation by sympathetic and parasympathetic systems, respectively.


The urethra receives visceral motor nerve fibers from the vaginal plexus and somatic nerve fibers from the sacral plexus.

The “urethral continence mechanism” involves striated as well as smooth muscle. The intrinsic (involuntary) element consists of inner, longitudinal and outer, circular layers of smooth muscle fibers that are continued downward from the detrusor muscle in the bladder neck. The external sphincter (sphincter urethrae or rhabdosphincter) consists of striated muscle fibers that encircle the urethra outside the circular layer of smooth muscle, with which they are blended. The voluntary sphincter urethrae has long been described as a planar ring of striated muscle lying on the upper surface of the perineal membrane. This view is outdated, but although modern accounts agree that an investment of striated muscle ascends along the urethra, they disagree as to how far it extends and where it is best developed.8,9,16

Visceral motor outflow enters the upper and middle thirds of the urethral wall in branches of the vaginal plexus.6,9 The intrinsic smooth muscle coat is permeated by a rich network of nerve fibers. Most are cholinergic and relatively few contain noradrenaline. This pattern resembles that of the detrusor, which is stimulated by acetylcholine and relaxed by noradrenaline. Yucel et al.6 have traced vesicular acetylcholine transporter- immunoreactive and neural nitric oxide synthase-immunoreac- tive fibers from the vaginal plexus into the muscle coat of the proximal urethra, and nitric oxide has been implicated in the relaxion of human detrusor muscle and urethral smooth muscle in a variety of animals.20 Somatic motor fibers enter the middle and lower thirds of the urethral wall through fine twigs from the perineal branch of the pudendal nerve. These are cholinergic and are destined for striated muscle of the rhabdosphincter.6,9 A number of authors report the existence of an intrapelvic somatic motor pathway to the external sphincter as well.8,19 These paths, all beginning in one way or another from the S2-4 ventral primary rami, are linked with the intrapelvic somatic innervation of levator ani. Again, they may represent normal individual variability and should not necessarily be discounted. However, recent studies employing computer-assisted 3-D reconstructions have failed to show any nerves descending from the pelvic cavity into the external sphincter.6,9 One of these studies, that of Yucel et al.,6 is especially telling, because the authors were able to distinguish between visceral fibers (branches of the vaginal plexus) that were neural nitric oxide synthase-immunoreactive and somatic fibers (branches of the pudendal nerve) that were not.

The human female is supplied with small periurethral glands. They are especially prevalent in the caudal third of the urethra, where, on each side, a larger group is drained by a common duct opening into the vestibule lateral to the urethral orifice. These are the paraurethral - or Skene’s - glands, which are gaining recognition as the “female prostate”.21,22 Little is usually said in the literature or in textbooks about the innervation of the urethral glands or blood vessels, but presumably they are regulated by the same mixture of adrenergic, cholinergic, and neural nitric oxide synathase-positive fiber types known to enter the urethral wall from the vaginal plexus.

The clitoris and bulbs of the vestibule

In the erectile tissues, parasympathetic stimulation results in arterial dilation leading to engorgement and erection; sympathetic stimulation, on the other hand, is thought to terminate erection by constricting local vessels.

The clitoris receives the bulk of its visceral motor innervation through descending branches of the vaginal plexus - the cavernous nerves. Vesicular acetylcholine transporter, neural nitric oxide synthase, calcitonin-gene-related peptide, and substance P all have been localized to nerves in the clitoris and in the intrapelvic visceral plexuses. Yucel et al.6 have shown recently that neural nitric oxide synthase-immunoreactive elements are not present in proximal branches of the pudendal nerve; instead, these presumptively vasodilator fibers are conveyed from the vaginal plexus in the cavernous nerves. Many pass directly to the corpus cavernosum and proximal body of the clitoris; others are added to the dorsal nerve for distribution along the shaft and to the glans. The density of neural nitric oxide synthase-positive nerve fibers in the glans is lower than in the corpora and clitoral body, but the level of endothelial nitric oxide synthase in vascular endothelium is proportionately higher.15 The sympathetic outflow pathway to the clitoris is less well defined. The most obvious route involves the hypogastric nerves, pelvic visceral plexuses, and cavernous nerves, but the pudendal nerve provides branches to the corpus cavernosum and body of the clitoris from the dorsal nerve. Although these may well be sensory in nature, they might also carry postganglionic sympathetic fibers added to the sacral plexus through gray communicating rami from the sympathetic chain.

Little appears to have been written about the innervation of the bulb of the vestibule, but presumably the pattern is similar to that of the clitoris. Certainly, the cavernous nerves pass very close to the bulb as they descend along the lower urethra,6,23 and the bulb receives a twig directly from the perineal branch of the pudendal nerve, which may carry sympathetic as well as sensory fibers.

Vestibular glands

Numerous small glands open into the vestibule, and on each side the greater vestibular gland (of Bartholin) lies in the connective tissue flanking the lower vagina. It is closely related to the caudal pole of the vestibular bulb, and its duct opens into the groove between the labium minus and the hymen. The vestibule itself is innervated largely by the perineal branch of the pudendal nerve, from which the greater vestibular gland receives a separate filament. Thus, the vestibular glands might receive postganglionic fibers added to the sacral ventral primary rami through gray communicating rami from the sympathetic chain. Little additional information is available, although the proximity of the cavernous nerves is suggestive.

Sources of sensory return

Sensory input is as important as motor outflow in sexual arousal, sexual pleasure, and orgasm, and such information comes from a variety of sources in the female perineum, external genitalia, vagina, cervix, and urethra. Some of these inputs are widely recognized and well understood; others are not.


The skin and subcutaneous tissues of the perineum and external genitalia are richly provided with touch, pressure, thermal, and pain receptors. Structurally, these can be classified as free nerve endings, endings associated with the hair follicles, endings associated with specialized epithelial cells (Merkle disks), and encapsulated endings (Pacinian corpuscles, Meissner’s corpuscles, Ruffini corpuscles, bulbous corpuscles of Krause, and others). The density of innervation is especially high in the prepuce and on the dorsal surface of the glans. In summarizing the distribution of various nerve endings in the vagina and external genitalia, Krantz24 noted a near absence of organized tactile receptors in the vestibule and clitoral body. This does not necessarily mean an absence of sensation, however, for cutaneous innervation is well documented in these areas, and subpopulations of free nerve endings are known to be responsive to light touch and temperature as well as to pain.1 As a rule, such somatic sensory input is conveyed to the spinal cord by fibers in branches of the ilioinguinal (L1), genitofemoral (L1-2), and pudendal (S2-4) nerves (Fig. 4.2.1).

The skin of the clitoris, glans, prepuce, labia minora, and vestibule presents a somewhat different picture. Here, in fetal human specimens, many nerve fibers have been shown to contain neural nitric oxide synthase in addition to the sensory transmitters calcitonin-gene-related peptide and substance P. The source of the calcitonin-gene-related peptide- and substance P-containing fibers has not been made clear, but those immunoreactive for neural nitric oxide synthase probably come through the vaginal plexus and cavernous nerves. Although there is no evidence that these nerves are sensory in nature, their presence seems to distinguish the skin in this region as distinct from that in the rest of the perineum.

Erectile tissues

Numerous branches of the perineal and dorsal clitoral nerves enter the substance of the clitoris and vestibular bulb as well as the clitoral tunica albuginea. Many if not all of these fibers are assumed to be sensory, and encapsulated mechanoreceptors have been found in the erectile tissues.

Vagina, cervix, and urethra

In the region of the introitus and hymen, the vagina is supplied with somatic sensory innervation through the perineal and inferior rectal branches of the pudendal nerve, whose fibers convey information from intraepithelial free nerve endings (pain) and scattered lamellated tactile endings in the submucosa.12,24 Above the hymen, the vagina and cervix receive visceral sensory fibers through the uterovaginal and vaginal plexuses. Numerous free nerve endings and occasional lamellar corpuscles occur in the endocervix; the vaginal portion, which is relatively insensitive to ordinary pain but not to stretch, is supplied with a smaller complement of free endings.

The degree and quality of visceral vaginal sensation is a matter of controversy. Although usually described as relatively insensitive to pain and touch, the vagina is also proposed as the site of the G-spot, alleged to be a highly erogenous zone located roughly a third of the way up the anterior vaginal wall.21,22 It is generally agreed that intraepithelial nerve terminals are rare in the vagina and that lamellated tactile endings are absent, except near the introitus. To some, this appears to rule out the existence of an entity such as the G-spot.21 However, there is now good evidence for a rich plexus of nerves immediately beneath the vaginal epithelium and in the lamina propria, many of which are not associated with blood vessels.11,12 A sizeable proportion of these small fibers contain sensory neurotransmitters (calcitonin-gene-related peptide, substance P, vasoactive intestinal polypeptide),11 and, as already mentioned, subpopulations of free nerve endings are sensitive to stretch, light mechanical touch, temperature, and pain. Therefore, pressure applied to the vaginal wall may elicit sensory return in the absence of “typical” tactile receptors. Furthermore, it has been suggested that pain may be elicited indirectly from hollow organs, such as the vagina, when shear or other mechanical stress leads to release of ATP from the lining epithelium. The purine then would diffuse across the basal lamina and bind to specific receptors on subepithelial nociceptive sensory neurons.25

Input from sensory endings in adjacent structures must also be considered. For example, the urethra, which is virtually embedded in the anterior vaginal wall, also possesses a submucosal network of fine nerves derived from the vaginal plexus and is encircled by its voluntary external sphincter. Like the urethra and the anal canal, the vagina itself descends through the pelvic floor into the perineum. As it does so, it is flanked closely by striated muscle fibers of the levator ani, some of which blend with its distal wall (see Chapter 4.4 in this volume). Above the levator, the vagina is invested by endopelvic visceral fascia, and the posterior wall of the vaginal vault is covered by the peritoneum of the rectouterine pouch. Thus, distention or displacement of the vagina during sexual activity could be expected to stimulate muscle spindles and other proprioceptive endings in voluntary musculature, visceral stretch and pressure receptors in the pelvic peritoneum and extraperitoneal connective tissues, and quite possibly endings in the urethra, either directly or through release of serotonin from paracrine cells in the urethral wall. (For a more detailed analysis, see Levin.26)

Central destinations of sensory input

Cutaneous sensation from the anterior urogenital region is carried to the upper lumbar spinal cord by the ilioinguinal and genitofemoral nerves. Sensory return from the remainder of the perineum, external genitalia, lower reproductive tract, and adjoining structures is carried centrally through either the pudendal nerve or the pelvic splanchnic nerves. Thus, somatic and visceral inputs converge on the S2-4 cord segments, where the information plays a crucial role in spinal reflexes and is directed upward to higher centers. Animal experiments, however, indicate that there may be an extraspinal sensory pathway to the brain,27 and this is supported by reports that in some women, conscious awareness of genital stimulation persists despite severe spinal cord injury.28 Although the vagus nerve has been suggested as the most likely extraspinal route, there is as yet no widely accepted anatomic evidence for this assumption.


From the above account, it can be seen that innervation of the human female perineum and lower reproductive tract is already fairly well documented in its broad outlines. It is also clear that recent studies using immunohistochemistry, computer-assisted reconstruction, and modern imaging technologies have made significant advances toward a more detailed understanding. There are, however, a number of areas that warrant concerted attention.

1. Courses of the intrapelvic neural pathways, so important to nerve-sparing surgical procedures, need to be more clearly defined. Although a great deal of information is available, it is scattered throughout the literature and is made less accessible owing to a lack of settled terminology. This is nowhere more evident than in descriptions of the intrapelvic “ligaments” and fascial planes that give passage to elements of the visceral nerve plexuses.

2. Mapping of the distribution of specific nerve fiber types needs to be completed. This work is already underway, but substantial gaps remain to be filled.

3. Functions of the different neurotransmitters need to be defined with greater precision, and this will have to involve localization of specific receptors in the tissues.

4. Finally, systematic studies are needed to characterize and map the distribution of sensory nerve terminals, especially in the clitoris, vestibule, vagina, and urethra.


The author is grateful to Dr Trudy Van Houten for her generous advice and support.


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