Both the somatic and the autonomic nervous system are involved in the regulation of female genital functions. The segments S 2-4 in the spinal cord are the most important segments. Most of the innervation to the internal genitalia goes from the spinal cord through the pelvic plexus. This nerve plexus is localised in the cervico-vaginal region. It is a combined sympathetic and parasympathetic structure, which also contains many nerve cells. The main somatic nerve innervating the external genitalia is the pudendal nerve. This nerve has a protective course and is thus mainly localised under or within the pelvic floor. The nerve ends in the dorsal clitoridal nerve but also sends branches to many muscles in the pelvic floor. There are also a number of somatic sensory nerves of other origin and somatic motor nerves direct from the spinal cord going above the pelvic floor.

The clitoris is one of the most sensitive areas of the human body. There are a number of sensory receptors for different qualities both in the clitoris and in the rest of the vulvar area. In the upper (proximal anterior) part of the vaginal wall, corresponding to the G spot area, there are many more nerve fibres than in other parts of the vaginal walls. There are indications of some sensory nerves from this area projecting directly to the brain stem though the vagus nerve. In the introitus there is a rich innervation of intraepithelial free nerve endings serving as pain receptors. The cavernosal nerves to the clitoris coming from the pelvic plexus are passing through the pelvic floor just beneath the urethra.

Key words: neurosexology, neuroanatomy, sympathetic nervous system, parasympathetic nervous system, pelvic plexus, pudendal nerve, cavernosal nerves, sensory nerve endings, clitoris, vagina, G-spot, lubrication, aquaporin.

Correspondence.

PO Lundberg

Department of Neuroscience. Neurology

University Hospital

S-751 85, Uppsala, Sweden.

Tel: +46 18 611 5026 Fax +46 18 611 5027

E-mail: PO.Lundberg@neurologi.uu.se

Introduction

Somatic and autonomic nerves

Both the somatic and the autonomic nervous system are involved in the regulation of genital functions. Efferent, outgoing nerves conveys motor, secretory and vascular function. Afferent, ingoing nerves mediate sensations from the external and internal genital organs. Sensory impulses may be transmitted through both the somatic and the autonomic nervous system.

The somatic sensory innervation of the skin and mucosa in the genital region is rather well recognised. However, the important sensory impulses from the internal genital organs including the blood vessels are less well studied, and partly still obscure. The somatic motor control concerns mainly nerves to the striated muscles in the different layers of the pelvic floor. The autonomic motor innervation regulates blood flow. In such a way erection of the clitoris and the other cavernous bodies can be achieved. Nerve stimulation of the pelvic nerves in animals has also been shown to result in an immediate translocation of the water channel protein aquaporin isoforms 1 and 2 from the cytosole compartment to the membrane compartment of the vaginal epithelium resulting in transport of water, the main part of lubrication into the vagina (1). The autonomic motor nerves also regulate secretory functions from the glandulae Bartholini and the paraurethral glands, the female prostate (2-3).

Traditionally the autonomic nervous system is on macro-anatomical grounds divided into the sympathetic nervous system and the parasympathetic nervous system. Basic pharmacological principles also follow this dichotomy. However, both systems are mixed in the pelvic plexus and many different transmitters and neuropeptids are found co-localized in the nerves, making it difficult to uphold this separation. The pudendal nerve starts as a pure somatic nerve but at the level of the clitoris it merges with the cavernousal nerves from the pelvic plexus controlling the vascular mechanisms in the spongiuous tissue of the clitoris. Besides there are nerve cells out in the pelvic plexus region. Axonal and local monosynaptic reflexes are important in the regulation of pelvic functions.

The peripheral innervation of the female genitalia has been reviewed by Lundberg (4-5). The central nervous regulation of sexual functions and abilities will not be dealt with in this review. An extensive description of central neural pathways involved in genital reflexes in the female can be found in (6). An analysis of this topic based on observations from clinical neurology can be found in (7-8),

The pelvic plexus

The pelvic plexus (the inferior hypogastric plexus) was first described by Frankenhäuser (9). This plexus has sympathetic connection through the superior hypogastric plexus. The pelvic plexus is situated in the region beneath the cervix uteri and the superior part of the vagina and rectum (10-16). It also extends frontally into the uterovaginal plexus (17).

The pelvic nerves, belonging to the sacral parasympathetic system, enter the pelvic plexus from the sacral segments S 2-4, but never from S 1 or S 5 (15, 18). There are direct connections between the sacral sympathetic chain and the pelvic plexus. They contain myelinated nerve fibres with a size as large as 11µ (15). Within the plexus there are, as mentioned, abundant nerve cells, jointly called the hypogastric ganglion or Frankenhäuser´s ganglion.

Most of the sensory innervation from the internal genitalia passes through the pelvic plexus. However, there are indications of a direct connection with the brain stem through the vagus nerve (19). Extirpation of the pelvic plexus and the ganglion of Frankenhäuser results in disappearance of pain of uterine origin. These structures may be damaged through surgical intervention near the uterus or the rectum (15).

Afferent (sensory) nerves

The innervation of the vulva

Clitoris is, besides the fingers, the most densely innervated part of the human surface area (20). Animal studies have shown that the number of nerve fibres in the dorsal clitoral nerve is double that of the dorsal penile nerve (21). The vibratory perception threshold of the clitoris is lower than that of the glans penis. Thus, clitoris is one of the most sensitive areas of the human body as regards exteroceptive stimuli. A woman can feel a vibration amplitude of 0.2-0.4 µ, which is about the same as the sensory threshold of the hands (22-24). The corresponding figure for the glans penis is considerably higher. The sensitivity thresholds increase somewhat in older ages but do not vary during the different phases of the menstrual, cycle (22).

The sensory nerves in the clitoris form an extensive network around the tunica of the corporeal body of the clitoris with a nerve-free zone at the midline 12 o’clock position (25). Most of the sensory impulses from the clitoris are conveyed via the bilateral dorsal clitoridal nerve. These nerves have a protected course through the urogenital diaphragm at the base of the clitoris, under the urogenital diaphragm and after that as a part of the pudendal nerves in Alcock´s canal. A protected localisation of an anatomical structure usually points to a special physiological importance of that structure, reached through evolution. Arteria dorsalis clitoridis accompanies nervus dorsalis clitoridis along the anterior surface of the corpus ossis pubis in sulcus nervi dorsalis clitoridis (26).

A precise knowledge of the course of the nerve in women is essential for the performance of some surgical procedures such as reduction clitoridoplasty in girls with adrenogenital syndrome, surgery for malformations of the urethra, and some types of surgery with insertion of vaginal tape for incontinence (26).

If any of these external genital nerves are damaged at an early age, the regenerative capacity seems to be good. Thus, an adult woman who has undergone circumcision with extirpation of the clitoris in early childhood may well have a vibration sensitivity threshold in this area of 0.4-1.0 µ in adulthood (5, 24). However, the cavernous tissue does not have the same capacity to regenerate. On the other hand, many other types of external trauma may result in damage to one or more of the other sensory nerves in the genital region. The most common causes are delivery traumas and episiotomies. When the pudendal nerve is blocked, e g as a part of childbirth anaesthesia, the clitoris is also anaesthetic. However, just because of the protected course of the dorsal clitoral nerve this particular nerve is usually not damaged during childbirth. Instead it is the perineal nerves and the anterior rectal nerves, both branches of the pudendal nerve that may be traumatizised. Intensive long distance cycling or spinning may result in an entrapment of the dorsal clitoral nerve, sometimes on both sides. The nerve is compressed against bone structures in an area where it does not have a protective course. Thus, the rather slim cycle saddle gives one type of damage. The horse saddle gives another type. During e g dressage riding there may be repetitive traumas to the perineal sensory nerves.

Nerve receptors

There are a substantial number of anatomical studies of the sensory receptors of the female clitoris (21, 27- 32). However, most of these studies are rather old and modern technique has not been used. There also exist some uncertainties concerning the nomenclature of the nerve endings.

There are three types of nerve endings in the clitorial area that can record exteroception. Such nerve endings are localised not only in the clitoris proper, but also in the inner labiae and around the urethral orifice. The most superficial layer of skin/mucosa contains free nerve endings. They mainly record pain. The impulses from these nerve ending are conveyed through very thin nerve fibres via somatic peripheral nerves and within the spinal cord at the low velocity of 1-2 m/sec. The so-called genital nerve corpuscles or mucocutaneous nerve endings (20) are localised beneath the skin- and mucosal layer. These nerve ending look like balls of yarn and have a central “nucleus”. It is believed that through this construction different types of stimuli can regulate the nerve corpuscles so that the cortical response changes in quality. The nerve endings react both for pressure and movements. These nerve impulses are conveyed via medium-thick, myelinated nerve fibres with a relative high velocity (40-60 m/sec) to the cerebral cortex. Along the nerves and the tendons surrounding the cavernous bodies there are rather large nerve ending built like onions with thick lamellae and a central nerve fibre. These nerve endings respond to deep pressure and vigorous movements. Nerve impulses are also conveyed through thick, myelinated nerve fibres to the cortex with a very high velocity (100 m/sec). The last two types of nerve endings are thus localised within or near cavernous tissues.

Signal traffic going via the spinal cord to the brain is influenced by an engorgement of cavernous tissues. Touch may thus be experienced as just touch or with a sexual quality dependent upon the degree of engorgement. Some of these nerve endings mentioned may be influenced by a number of factors such as sex hormone levels in the tissues. Androgens are more important in the upper part of the vulva and estrogens in the region close to the vagina. Thus, the transition from vagina to vulva is marked by an increase in androgen and a decrease in estrogen and progesterone receptors (33). Estrogen deficiency may result in a change in the quality of sensation so that touch may be experienced as disagreeable instead of pleasurable

Nerve endings responding to pain and pressure are abundant not only in the clitoris but also in the labia minora and majora (32). Tactile nerve endings are most abundant in labia majora, where the innervation is more similar to that of the rest of the hairy part of skin. The vibratory perception thresholds for labia majora vary between 0.5 and 1.5 µ (24). Clitoral cold and warmth sensory thresholds can also be tested with very exact methods. The mean threshold for cold tested at the clitoris is about 35 degrees C and for warmth 38 degrees C. A very simple way to test cold sensitivity is just to drop a few drops of olive oil of room temperature (21 degree C) at the level of the clitoris and let it run down the vulva. Temperature sensitivity is better at the upper level of the vulva than in the perineum.

Reflexes elicited from the clitoris

There are two reflexes that can be evoked from the clitoris, one phasic, and the other tonic. The bulbocavernosus reflex is a spinal, somatic and bilateral phasic reflex. The reflex arc goes through the pudendal nerves and the reflex centre lies in the sacral cord segments 2-3. The reflex can be elicited by pinching the glans. This results in a contraction of the bulbocavernosus and external anal sphincter muscle (34-35). The tonic reflex has been less well studied. Vibratory stimulation of the clitoris causes sustained contraction of pelvic floor muscles (36).

The innervation of the vagina and the uterine cervix.

It has been considered that the area between the urethra and the vaginal wall, the so-called Halban´s “fascia” is richly innervated. (32,37) In a study of the innervation of the human vaginal mucosa it was found that the distal areas of the vaginal walls had more nerve fibres than the proximal parts (38). In the anterior wall an extreme number of richly innervated and non-innervated blood vessels could be seen. The anterior wall was more densely innervated than the posterior. In some cases large nerve coils were observed in the anterior wall. In another study no vaginal location with increased nerve density was found (39). The vaginal cuff showed slightly fewer nerves than the anterior and posterior wall.

The function of the nerves observed has not been definitely determined. However, they are considered to be a mixture of sensory and autonomic nerves. Free intraepithelial nerve endings were only detected in the introitus vaginae region and hymeneal ring (32). These nerve endings are considered to be mainly pain receptors. It is probably from these nerve ending that nociceptive pain (hyperalgesia) in e g vulvar vestibulitis is typically elicited by touch. It has been shown that in this particular condition these nerve endings containing the neuropeptid CGRP (calciotonin-related peptide) are increased in number (40-42). It is important to understand that pain from introitus is conveyed through the somatic nervous system and pain from the inner two parts of the vaginal and the cervix is transmitted through the autonomic nervous system. Somatic pain is more precisely localized and has another character than autonomic nervous system pain that is more diffuse, with a different character and can be referred metamerically, thus related to the embryonic development of the nervous system.

Other sensory receptors are localised at several places in the vaginal walls and its surroundings. Muscle spindles have been found in the vaginal wall muscles. These spindles are sensory organs sensitive to changes in length of the muscle and to the velocity of such changes (43). It has been suggested that stretching of the sacrouterine ligaments is the mechanism most important for orgasm in women (44).

Temperature sensibility, especially cold sensitivity, in this part of the human body is of particular importance. It is this sensory quality that makes it possible for us to differentiate between gases, fluid and solid content in the rectum (45). The discriminative quality of touch is less developed than temperature sensitivity within the internal pelvic organs. It difficult to discriminate between different size and form of an object inserted into the vagina (46). This fact has forensic significance. It is common knowledge that a round object, such as the penis, inserted in the vagina gives less discomfort/more sexual arousal than an asymmetrical object.

Vaginal sensitivity to electric stimuli has been studied in women (47). It was found that the genital area including the clitoris had a low sensitivity for this type of stimulation in comparison with that of the hands. The vaginal walls above the introitus were found to be very insensitive. A relative sensitive position could be detected at the 12-hour position that is in the anterior wall. Neurophysiologic methods for studying vaginal sensitivity have been developed (48). However, in clinical practise it is usually sufficient to ask if the patient can recognise if the stimulus is on the left or the right side in the vagina. If an object or a finger is for a moment pressed against the anterior vaginal wall, a technique that also stimulates the urethra, most patient can localise a sensation to the urethra or the bladder. This feeling indicates normal sensitivity or hyperaesthesia. Neurophysiologic methods for studying urethral sensitivity have also been developed (7, 49-50).

Analgesia produced by vaginal stimulation

Animal experiments have shown that vaginal and cervical stimulation results in a series of physiological reactions in the body. One of these effects is the producing of analgesia (51) Thus, intense mechanical stimulation of the anterior wall of the vagina, the so-called G spot area (52), leads to a pronounced increase of the thresholds for pain detection and pain tolerance in the whole body (53-54). Mechanical stimulation of this part of the vagina may also result in sexual arousal (55). Thus, this type of stimulation brings about a hypoalgesia but not a hypoaesthesia. Such a hypoalgesia can neither be achieved through stimulation of the posterior wall of the vagina, nor of the clitoris.

This analgesic function occurs naturally during labour in women (56). The anatomical correlates of this physiological control mechanism are not fully known. Afferent paths go through the pelvic nerves in rats (57), but probably also through somatic nerve fibres to S 3-4 above the pelvic floor. Studies on rats suggest that glutamate is involved in the transmission of sensory signals, such as pain, from the cervix to the lumbospinal cord in parturition (58). Other studies on rats with spinal cord transections support the idea that this pain blockade may be also mediated through the vagus nerve (59). fMRI studies of the human brain during vaginocervical self stimulation and orgasm in women with complete spinal cord injuries have shown an activation of the sensory vagus nuclei in the brain stem (19) This also supports the concept that sensory impulses from the pelvic plexus can reach the central nervous system through the vagus nerve.

The main pain afferents from the cervix goes through the hypogastric nerves foremost to the lumbar 1 root ganglion. It has been shown in animal experiments that these ganglia express transient receptor potential vanilloid type 1 (TRPV1) channel and calciotonin gene related peptide (CGRP), but not P2X3 receptor or somatostatin (60. This combination makes the actual pain afferents unique which may play a role in estrogen-induced sensitization of afferents from the uterine cervix.

Efferent innervation of the pelvic floor

The muscles of the pelvic floor

The pelvic floor has two layers of striated muscles: The outer layer is called the urogenital diaphragm. This is localised in the anterior part of the floor where the urethra and the vagina are passing. The deeper layer is called the pelvic diaphragm. Besides the urethra and the vagina the rectum is also passing though this muscle layer: These striated muscles of the pelvic floor are innervated from the so-called Onuf´s nucleus at the spinal sacral segments 2-5 (61). In the pelvic floor there are also a number of muscles having pure sphincter function.

The striated muscles of the pelvic floor are of two types, type 1 and type 2 (62). The fibre diameters are small. Type 1 fibres are aerobic and can produce a long-lasting tonic contraction. In such a way continence is maintained. Type 2 fibres, mainly glycolytic, can rapidly, but only for a short period of time, strengthen the contraction and in such a way maintain continence in a stress situation. Spontaneous contractions occur in the resting, sexually unstimulated vagina (63).

The pelvic floor muscles have estrogen receptors (64). A minimum estrogen level in the tissue is necessary for the maintenance of continence. There are also androgen receptors in the muscles. Androgens are of great importance for the development of the pelvic muscles. In fact, measurement of an increase of the mass of these muscles in male rats was historically one of the best biological methods to assay testosterone. The striated pelvic floor muscles are innervated from below through the pudendal nerve (the muscles of the urogenital diaphragm) and from above (65-66) directly from the pudendal plexus sacral segments 3-5 (the pubococcygeus muscle).

Delivery may cause considerable damage both to muscles and nerves (67) of the pelvic floor. This can be judged by measurements of pudendal nerve terminal motor latency (68) as well as by electromyography. However, in most instances there is a good recovery after some time (69). To have a normal and fit pelvic floor muscle function is believed to be of importance both of the orgasm capacity and for pleasure at sexual encounters (70).

Nociceptive pain stimulation results in a reflexogenic muscle contraction in this area as well as in many other muscles of the body. Sustained contractions of striated muscles usually result in pain and tenderness of the muscles because of poor oxygenation and increase of lactic acid. These defence mechanisms are often seen in the pelvic floor of women. A typical example is that found in vulvar vestibulitis and also in many other vulvo-vaginal disorders with nociceptive pain. An attempt to have intercourse, even just a touch of the painful area with a cotton-tipped applicator may result in a painful contraction of the pelvic floor muscles, especially the levator ani muscle or pubococcygeus muscle. Thus, an important measure in treatment of such conditions should be to teach these women not only to contract but more important to relax their pelvic floor muscles (71). This is most easily done in a position where the pelvic floor muscles are actively relaxed through reciprocal inhibition.

In the clinical setting the striated pelvic floor muscles can best be studied though palpation. However, there are a number of neurophysiologic techniques that can also be used (7, 49-50).

Innervation of the cavernous tissue of the clitoris, bulbus vestibulae, labiae and vagina

Glans clitoridis is homologous to the glans penis and crura clitoridis to the two corpora cavernosa of the penis (72). Both glans and crura contains cavernous tissue and are surrounded by a firm tunica. Homologous to the corpus spongiosum of the male there are the vestibular bulbs split in two on each side of the urethral and vaginal orifices.

The bulbs have a very close anatomical as well as functional connection with both the clitoris and the urethra (73) Hence it has been suggested that they should be called the bulbs of clitoris instead of the bulbs of vestibulum. They are also important in the role of protection of the pudendal nerve during intercourse. The bulbs are very variable in size in women. It is said, but not scientifically proven, that they increase in size with the frequency of sexual intercourse.

At sexual stimulation there is a more or less pronounced erection of the clitoris. Interviews in detail of women usually disclose that they actually have noticed erection of the clitoris, however not during all sexual encounters. The erection of the clitoris may not be simultaneous in time with vaginal lubrication. It usually needs more intense sexual stimulation. It increases the sexual arousal. Certain prescription drugs (trazodon, fluoxetine, sertralin and bromocriptin) well as a number of spinal cord disorders have been described in connection with a true priapism of the clitoris (74).

The perineal urethra is embedded in the anterior vaginal wall and is surrounded by a vascular tissue in all directions except posteriorly where it relates to the anterior vaginal wall (75). This vascular tissue may be considered as homologous with the most proximal part of the spongious body of the male,

The ischiocavernosus muscle surrounding each of the two crura also takes part in the erection mechanism of the clitoris. There is an increased blood volume in the preputium of the clitoris at arousal. This phenomenon as well as the tonic contraction of the ischiocavernosus muscles brings about an elevation of the clitoris, which seems to disappear. Neurostimulation of the pudendal nerve in dogs results in compression of the clitoris by the ischiocavernosus muscles (76). The bulbocavernosus muscle surrounds the vestibular bulbs, then goes forward and inserts at the dorsal surface of the clitoris. Thus, the muscles on both sides together form a sling around the clitoris. Contraction of these muscles increases clitoral erection through a mechanism compressing the dorsal vein of the clitoris. It also compresses the cavernous tissue on both sides of the introitus, the bulbus vestibuli. Passive dilatation of the vagina results in a reflectoric contraction of both the bulbo- and ischiocavernosus muscles (77). Stimulation of the glans clitoridis effects an increase in vaginal EMG activity and pressure indicating vaginal wall contractions (78) Direct vaginal stimulation, caused by movements of the penis, may indirectly affect clitoris and sensory perception from the clitoris.

The innervation of the cavernous tissue comes from the pelvic plexus via the uterovaginal plexus through the cavernous nerves on both sides. Electrical stimulation of the cavernous nerves in dogs results in an increase in blood flow of the internal pudendal artery giving an erection of the clitoris (76). The cavernous nerves pass through the pelvic floor beneath the urethra (75). Thus, these nerves may be damaged in certain types of incontinence surgery. In rats there is an increase in clitoral blood flow following both clitoral and pelvic plexus stimulation. Vaginal blood flow is increased only after pelvic plexus stimulation (79). Also, electrical stimulation of the anterior roots S2 and S3, but not of S4, in women results in an increased vaginal blood flow (80). Animal experiments (81) have shown that electrical stimulation of the pudendal nerve results in an increase in vaginal blood flow which is abolished by cutting the pelvic nerves but not but cutting the hypogastric nerves.

Neuropeptides and other neurotransmitters

In the clitoris there is an abundant peptidergic innervation (82). Thus, co-localization studies showed the co-existence of vasoactive intestinal peptide (VIP), peptide histidine methionine (PHM), and partly helospectin and neuropeptide Y within nerve fibres in the cavernous tissue as well as substance P and calcitonin gene-related peptide (CGRP) co-expression in nerve fibres especially underneath and within the glans clitoris.

VIP is present both in Frankenhäuser´s ganglion and in nerve fibres in the vaginal mucosa (83). Systemic infusion of VIP, as well as local injection of VIP in the vaginal wall results in a dose dependent increase in vaginal blood flow. VIP also gives vaginal lubrication (84). Nerve fibres containing VIP have also been localised at or near the ducts of the paraurethral glands (2, 85). Thus these nerves may be of importance for the urethral lubrication and thus female ejaculation. However, there are many other candidates in the urethra for such function, as release of noradrenaline and stimulation of smooth muscle alpha1-adrenoreceptors (86) Sexual stimulation leads to an increase in blood VIP (83). VIP has physiological effects on the uterus. It relaxes the isthmus and gives uterine vasodilatation.

Two other peptides of the same vasoactive peptide family as VIP, helospectin and pituitary adenylate cyclase activation polypeptide (PACAP) have been found in the mucous membranes of the human vagina and in the walls of small vessels (87). Also peptide histidine methionine (PHM) and peptide histidine valine (PHV) are present and biologically active in the human vagina and cervix (88-89).

Nitric oxide is of importance for clitoral erection since neuronal nitric oxide synthase (nNOS) immunoreactivity has been detected in nerve bundles and nerve fibres within the human glans clitoridis and corpora cavernosae of the clitoris (90), in details studied in rats (91). Also in labia minora of young girls nNOS have been visualized co-localized with silver stained nerve bundles (92).

In an extensive study (93) of female human pelvic specimens at 14 to 34 weeks of gestation by immunohistochemical methods it was found that the dorsal nerve of clitoris receives nNOS positive branches from the cavernousal nerves. These nerves occupies the 2 and 10 o’clock positions on the anterolateral side of the vagina and follows the urethra at the 5 and 7 o’clock positions. The nerve bundles innervate the cavernous body of the clitoris. The most distal part of the clitoris, the glans, was only innervated by CGRP (calcitonin gene related peptide) and SP (substance P), which are considered primary sensory neuropeptides.

Structural proteins

Not only neuropeptides but also a number of structural proteins are of importance for the function of the vagina. Of special interest is ezrin that modulates vaginal cell-to-cell interaction in processes such as the elasticity of the vagina (94). Ezrin production is stimulated by estradiol. The neural regulation of this process is however not known.

Peripheral ganglion cells

Ganglion cells are found in the adventitia surrounding the vagina (32). In the upper third of the vagina they are frequently seen between the bladder and the vaginal wall. The human vagina is densely innervated by adrenergic nerves that are sympathetic in origin (95). Cholinesterase positive nerves are found around blood vessels. Paracervical ganglia contain NADPH diaphorase-reactive nerve fibres, that appear to play an important role in the regulation of uterine vascular tone by liberating nitric oxide (96). In the bovine vagina both substance P, VIP, neuropeptide Y and NO were found in the vaginal wall and in paracervical ganglia (97). In animal experiments (rabbit) it has been found that angiotensin II is involved in the regulation of clitoral cavernous smooth muscle tone via angiotensin receptors (98) Nitrergic transmission is partly responsible for the relaxation (99). In the rat the neurons of the pelvic plexus going to vascular and nonvascular smooth muscles co-express both VIP and NPY (100). However, noradrenergic neurons seem to have a limited importance.

Inter- and intraindividual variations in female genital neuroanatomy.

It is important to remember that no other organ system of the human body, than the internal genitalia of the female, has in a short time to be able to adapt in form and size and also in topography to serve entirely different functions during sexual intercourse, sperm transport, implantation, gestation and delivery. The nerve bundles have for example to take much longer routes and also have to be protected in special ways. This is illustrated by f ex the course of the dorsal clitoral nerve and the very tortuous course of the nerves in the anterior part of the vagina. This corresponds well with the MRI finding of Weijmar Schultz et al (101) that the anterior wall of the vagina is lengthen during coitus in the missionary position.

Most studies of the neuroanatomy of the female reproductive tract have been done on animals, or aborted embryos or at the best in single deceased women. So far only a limited number of studies have been performed using modern techniques such as fMRI and ultrasound on healthy living women. It is also clear that there are many individual differences based on genetic mechanisms even as regards neuroanatomy. Examples of this are the size of clitoris and labia minora and the distance between the vaginal introitus and the anus. This does influence the peripheral innervation.

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