Download Neuropelveologic etiologies and management of

Neuropelveologic etiologies and management of intractable Vulvodynia
Univ.-Prof. Prof. Dr. med. Marc Possover, MD, PhD
Introduction
Vulvodynia is a chronic pain syndrome affecting respectively the vulva and occurs without an identifiable
cause or visible pathology. The pain is usually characterized as a burning, stinging, irritation or sharp pain that
occurs in the vulva, including the labia. It may be constant, intermittent or happening only when the vulva or the
vagina is touched or while sitting, but is usually defined as lasting for years. The incidence of vulvodynia is not
known but it is clearly more common than is generally thought and induces a dys- or even an apareunia in about
15% of women [1]. Although vulvodynia was described in the literature in the late 1800s, many questions about its
epidemiology and risk factors remain [2]. There has been a tremendous effort to diagnose and treat vulvodynia over
the last 15 years, but there is a need for comprehensive information on vulvare pain and on pathologies of the pelvic
nerves as potential etiology.
Innervation of vulva and of vagina
Since pain is a signal that is perceived by peripheral nerves that conveys sensoric signals throughout the
body to the central nervous system, location of pain do not systematically correspond with the origin of pain but just
indicate through which nerves the pain signal is transmitted to the brain. Therefore, history about exact location and
irradiation of pain and an absolute knowledge about corresponding innervations of these areas is essential for
management such pain syndromes. The female genital organ has several parallel nerve systems. The most important
nerve groups are the pudendal nerve, which has chiefly S2-4 derivation, the inferior hypogastric plexus and the
genital branches of the genitofemoral nerve.

Sensory supply to the vulvar, perinal and perianal skin and subcutaneous tissue of the lower 2/3 of the
vagina is the pudendal nerve. Efferent somatic supply is not significant in the vaginal wall since there is
no striated muscle, but efferent supply largely from the pudendal nerve controls the levator muscles that
provide support, and influence function of the lower third of the vagina.

Visceral nerve supply which has chiefly hypogastric plexus derivation from T1-L2, is significant for the
upper vagina, musculature, and glands. These nerves arise from the inferior hypogastric plexus, which
gives rise to three other divisions. One division is the uterovaginal plexus (Frankenhausen's plexus) around
the ureter and uterine artery. Fibers from the uterovaginal plexus accompany the vaginal artery and vein to
the vagina. Parietal peritoneum in the pouch of Douglas is supplied by the visceral afferent nerves of the
uterovaginal plexus. No parasympathetic fibers have been described in association with this hypogastric
innervation of the vagina. The chief importance of vaginal parasympathetic efferent fibers (S2-4) is to
mediate sexual response in the lower portion of the vagina.

The genitofemoral nerve originates from the upper part of the lumbar plexus of spinal nerves. Its roots are
L1 and L2 (lumbar). In females, the genital branch of the genitofemroal nerve ends in the skin of the mons
pubis and labia majora.
In view of these anatomical considerations and in absence of spinal cord pathologies, vulvodynies correspond to
pathologies of the genitofemoral nerve and/or of the pudendal nerve and/or of the sacral nerves roots, “midlle
vagidonydies” to pathologies of the pelvic floor and “high vaginodynies” to pathologies of the hypogastric nerves
and plexuses.
Diagnosis
The term vulvodynia is reserved for those patients suffering from such chronic pain that occur in the absence of
physical findings [3]. Conditions of infectious, inflammatory, neoplastic, and immunologic origin, as well as
evidence for any systemic illness, physical trauma to the vulva, dermatologic conditions, and urinary tract
syndromes should be ruled out prior to making such a diagnosis. The diagnosis is then based on the typical
complaints of the patients, normal gynecological and dermatological findings, and the absence of identifiable
causes. History has to focuses on all symptoms such as allodynia, numbness, hypersensitivity, electric shock or
stabbing pain, knife-like or aching pain, feeling of a lump or foreign body, twisting or pinching, abnormal
temperature sensations, constipation, pain and straining with bowel movements, straining or burning when urinating,
painful intercourse, and sexual dysfunction, including hyperarousal and hyposensitivity. An accurate diagnosis
requires a comprehensive history focusing on genital and extragenital (lumbosacral areas) symptoms as well as on
information’s about previous surgical/obstetrical procedures and pelvic pathologies. Also information’s on possible
pathologies of the CNS (spinal cord lesions, multiple sclerosis, Lyme disease…), and dysfunctions of the peripheral
nervous system such as motor deficits of hip adduction (L3/Obturator Nerve), knee extensors (L1-L4/Femoral
Nerve), ankle dorsiflexion (foot drop – L5) and ankle plantar flexion (S1) are of major importance. Sphincters
dysfunctions, motor/sensitive urinary urgency or voiding difficulties are explored by urodynamic testing.
Clinical examination focuses on inspection of the genital organs, supported by a vaginal culture, an urinanalysis, a
control of vaginal pH, Pap smear, biopsy of abnormal vulvar areas and a psychosocial assessment. Neurologic
examination should include exploration of all lumbosacral nerves with vaginal/rectal palpation of the pudendal
nerves and the sacral nerves roots S3-5: apparition of a exquisite tenderness and a Tinel´s sign (sensation of tingling
or "pins and needles" in the distribution of the damages nerve) when digital pressure is applied over a pelvic nerve,
and improvement in pain when a selective block of the nerve is used, confirm unequivocally the diagnosis.
Differencial diagnosis
There are numerous possible causes for vulvodynia but the most frequent one are of dermatologic origin
(table 1). In postmenopausal women, atrophic vaginitis can also cause burning pain. Yeast and lichen simplex
chronicus typically produce itching, although sometimes they can present with irritation and pain, so they must be
considered in the differential diagnosis. Lichen sclerosus manifests as white epithelium that has a crinkling, shiny,
or waxy texture. It can produce pain, especially dyspareunia. The pain is caused by erosions that arise from fragility
and introital narrowing and inelasticity. Vulvovaginal lichen planus is usually erosive and preferentially affects
mucous membranes, especially the vestibule; it sometimes affects the vagina and mouth, as well.
In regard to infection, Candida albicans and bacterial vaginosis are usually the first conditions that are considered,
but they are not common causes of vulvar pain and are never causes of chronic vulvar pain. Very rarely they may
cause recurrent pain that clears, at least briefly, with treatment. Herpes simplex virus is very frequently evocated as
a potential cause for vulvodynia, but is usually a cause of recurrent but not chronic pain. Chronic pain is more likely
to be caused by skin disease than by infection. Lichen simplex chronicus causes itching; any pain is due to erosions
from scratching. Skin diseases that affect the vulva are usually pruritic - pain is a later sign. Lichen simplex
chronicus (also known as eczema) is pruritus caused by any irritant; any pain that arises is produced by visible
excoriations from scratching.
It is always important to consider cancer when a patient has an abnormal vulvar appearance and pain that has
persisted despite treatment.
Neuropathic etiologies and corresponding treatments
Pudendal neuralgia (PN), diabetic neuropathy, and post-herpetic neuralgia are the most common specific neurologic
causes of vulvar pain reported in the literature. Some of the possible causes are then an inflammatory or
autoimmune illness or frequent infections. Multiple sclerosis can also produce such pain. An involvement of the
nervous system in any form is supported by the fact that women suffering from vulvo-vaginodynia often report a
history of headache, irritable bowel syndrome [4], interstitial cystitis [5,6,7], fibromyalgia [8], chronic fatigue
syndrome, back pain, and temporomandibular joint disorder. Several studies have noted an increase in anxiety,
stress, and depression among women who have vulvodynia [9,10]. These comorbidities are particularly helpful in
establishing the diagnosis of a neurological etiology.
Distal lesions of the pudendal branches – There are vulvodynias mostly located in the dorsal portion of the vulva
and are often secondary to obstetrical or proctological procedures with damages of the middle or the dorsal branch
of the pudendal nerve. A superficial vulvar trigger point is found while palpation of the pelvic nerves is normal.
Pelvic organs dysfunctions are lacking. Improvement in pain by lidocaine infiltration of the trigger point confirms
the diagnosis and treatment consist then in same local infiltrations with botulinum toxine A.
Genitofemoral neuropathy - When the genitofemoral nerve is affected, pain may be felt in the inguinal area with
irradiation in the internal aspect of the thigh and in the genital area. Distal lesions of the genital branch of the
genitofemoral nerve induce a anterior vulvodynia. Since the genitofemoral nerve is only sensitive, symptoms are
restricted to sensory changes except in male in who loss of cremastic reflex can be observed. Surgical access to the
inguinal region (appendectomy, herniorraphia, introduction of lateral trocar for laparoscopy…) exposes patients to
risk for such groin pain that has proven to be an extremely difficult problem to treat [11]. Nerve blockade with
anesthetic agent or botulinum toxine A is the method of choice as well for diagnosis as for treatment especially.
However in failure of medical treatments, several conservative (neurolysis, removal of the mesh) and ablative
(neurectomy) procedures doe exist [12,13]. The current most propagated technique is the triple neurectomy
developed by Amid that consist in a neurectomy to all three inguinal nerves (the ilioinguinal, iliohypogastric and the
genitofemoral nerve) with a insertion of the proximal cut ends of the nerves under the internal oblique muscle fibers
[14]. However, taking into consideration the underlying cause, location, and type of pain, attempts at conservative
procedure should almost always be considered before moving to destructive procedures [15]. It is well accepted that
the actual state of the art neurosurgical treatment of peripheral neuropathic pain is neuromodulation that is an
important part of the continuum of managing chronic intractable pain. Several techniques of electrodes implantation
has been described ranged from the epidural implantation [16], the subcutaneous implantation [17], and the direct
implantation of an electrode to the endopelvic portion of the nerves by laparoscopic approach [18].
Pudendal neuralgia (PN) PN is reserved for women with neuropathic pain in the entire nerve distribution - vulvar,
perineal and perianal area – with typically worsening by sitting, relieved by standing, and absent when recumbent or
when on a toilet seat. Various further symptoms such as urinary hesitancy, frequency, urgency, constipation/painful
bowel movements, reduced awareness of defecation, sexual dysfunction including loss of libido can be observed.
There are numerous possible causes for PN. Some of them are an inflammatory or autoimmune illness,
frequent infections. After iatrogenic nerve damages, which are frequent in obstetrics and gynecology, PN is
common, with etiologies such as compression of the nerve through a postpartal haematoma, fibrosis of the
ischiorectal fossa, stretching of the nerve during delivery or surgical damages during transvaginal sacrospinous
colpopexy [19]. More recent interventions using mesh material for sacrospinal fixation [20], sacro-colpopexy or
rectopexy may also expose patients to risk for pudendal nerves damages.
Neurological examination is extremely important for diagnosis. Extrinsic lesions do not include pudendal
numbness or troubles of micturition or continence, but imply hyperesthesia. In neurogenic nerve damages,
numbness is usually combined with anal deviation (perineal/perianal myoatrophia), normal micturition or eventually
bladder overactivity [21]; urinary incontinence occurs only in bilateral lesions.
For diagnosis, the more commonly used tests are the PN motor latency test (PNMLT), electromyography (EMG),
diagnostic nerve blocks, and magnetic resonance neurography (MRN). EMG studies of the pudendal nerve, often
touted as a diagnostic tool, are unreliable since they can be abnormal after vaginal delivery or vaginal hysterectomy
and do not define the neurologic level of the pathology. Transvaginal/transrectal palpation and blockade of the
pudendal nerve is the key of the diagnosis.
There are many treatment options depending on the cause of the PN. Reduction or stopping association of
medical pain treatment may be the first step in recovery urinary functions, since most pain killers present side
effects on bladder and sphincters control.
Because excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the
pelvic pain syndromes, treatment options include always pelvic floor physical therapy to relax pelvic floor muscles
and pain medications. Trial of pudendal nerve blocks with botulinum toxine A is a real option [22], but bilateral
infiltration must be done carefully to avoid urinary or fecal incontinence.
Where medical treatments are not successful, surgical treatments may be tried. Surgery is then designed to
decompress the injured pudendal nerve by transgluteal, perineal or laparoscopic approach [23,24,25]. However,
nerve decompression may not be effective in neurogenic lesions of the nerve. It is well accepted that the actual state
of the art neurosurgical treatment of such neurogenic pain situations is the neuromodulation. Because sacral nerve
stimulation does not permit neuromodulation of all pudendal afferent fibres together, it has not been considered to
be a real therapeutic option for PN in the international medical literature [26]. Spinelli has reported about the
technique of implantation of a tined lead near the nerve by perineal or posterior approach [27]; this technique
exposes the patients for risk for lead migration, dislocation or even cable breakage. The laparoscopic technique of
implantation called “LION procedure” [28], enable a safe and reproducible implantation of an electrode array in
direct contact to the PN within the protection of the pelvis.
Sacral radiculopathies (SR) - The diagnosis of PN is often overdiagnosed: “pudendal neuralgia” with pain
irradiation in the buttock or the legs is not a PN, but a sacral radiculopathy. The semeiology is very subtle
combining pelvic pain, dys/apareunia, troubles/loss of vesical and/or rectal sensation, pudendal pain (S2-4), vulvovaginodynia and coccygodynia (S3-4), sciatica (L5-S2 with “non-pelvic symptoms” such as low-back-pain
(lumbosacral trunk, L5), pain and/or abnormal sensations in the legs or in the buttom.
Surgical damages, endometriosis and compression of the sacral nerve roots (SNR) - sacral compartment syndrome are the most frequent etiologies for SR.
In SR secondary to surgical interventions, damages of the nerves are manifold, and most are due to lack in
knowledge on pelvic neuroanatomy but also to mistakes of the surgical technique: section of the nerves, ligature
entrapment, traction and clamping injury, suction by continuous blood aspiration near the nerves, compression,
contusion, pressure, ischemia by excessive dissection, cutting and electrical or thermal injury. Such intraoperative
nerves damages happening are responsible for neuropathic pain with neurologic troubles starting quite immediately
after the procedure. In contrast, nerves entrapment by postoperative fibrosis or pelvic varicosis veins compression
requires months or years to develop [29].
In all nerves damages secondary to pelvic procedures, the laparoscopic exploration of the injured nerves for possible
decompression must be then indicated as soon as possible, before nerve damages become irreversible and process of
chronification and memorization of pain begin.
In endometriosis of the SNR, pains are cyclical, progressive over the time and triggered by the menstruation. In
massive involvement, troubles of locomotion and pelvic organs dysfunctions may occur. Laparoscopic exploration
enables as well the confirmation of the diagnosis as an adapted treatment based on the decompression of the nerves
and resection of endometriosis [30].
SR by “pelvic compartment syndrome” must also be considered as a potential etiology. The pain is increased by all
situations that increase pelvic venous pressure (prolonged standing and sitting position…), or by any marked
pulsation of the pelvic veins (tricuspid insufficient, close anatomic relationship with arteries…). Because pelvic and
lower limb veins are similarly in constitution, patients with varicose in the legs should present a higher risk for
pelvic varicose veins. Also pelvic interventions and pelvic vein thrombosis may promote changes in pelvic veins
circulation.
Further rare diagnosis such as sacral tumors or pelvic nerves tumors can also be evocated as potential etiologies.
Laparoscopy enables also in these indications an etiologic diagnosis and treatment by decompression of the SNR.
Conclusion
Vaginodynia are not life-threatening complains that affect million of women’s over the world. Such pain have a
huge impact on a woman´s life, and because the diagnosis is often omitted, many women may remain isolated by a
condition that is not easy to discuss. Treatment for vulvodynia may be adapted to a possible etiology, even when
medical pain treatments are then still the most frequent used in daily medical practice. Unfortunately, pathologies of
the pelvic nerves as potential etiologies are widely omitted. The aim of this manuscript is to draw the attention of
physicians and gynecologists on the neurologic aspects of such a gynecologic pain situation. For a proper
neuropelveological diagnosis, all information’s obtained by a detailed history, in combination with both
gynecological and neurological assessment are essential. While the genitofemoral and pudendal nerves are
accessible for local treatments such as infiltrations, in sacral radiculopathies, laparoscopic exploration have to be
considered as the step of choice, since it may result not only in a proper etiological diagnosis but also in a
successfully minimal invasive neurosurgical treatment.
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Table 1: Gynecologic /dermatologic conditions for vulvo-vaginal pain
Acute irritant contact dermatitis (e.g., erosion due to podofilox, imiquimod, cantharidin, fluorouracil, or
podophyllin toxin)
Aphthous ulcer
Atrophy
Bartholin’s abscess
Candidiasis
Carcinoma
Chronic irritant contact dermatitis
Endometriosis
Herpes (simplex and zoster)
Immunobullous diseases (including cicatricial pemphigoid, pemphigus vulgaris, linear immunoglobulin A
disease, etc.)
Lichen planus
Lichen sclerosus
Podophyllin overdose (see above)
Prolapsed urethra
Sjögren’s syndrome
Trauma
Trichomoniasis
Vulvar intraepithelial neoplasia
Table 2: Neuropelveologic etiologies and corresponding symptoms
Vulvodynia

Pathologies of the genitofemoral nerve

Pathologies of the pudendal nerve

Sacral radiculopathies
Groin pain - anterior vulvodynia Thigh pain - normal bladder functions
In neurogenic lesions: inguino-genital hyposethesia
Isolated pudendal pain (all three areas)
No irradiations
Normal bladder functions or OAB or bladder
hypersensitivity
Urinary/fecal incontinence only in bilateral
neurogenic lesions (pudendal hypoesthesia)
Trigger point and Tinel sign by palpation of the
pudendal nerve
Irradiations in pudendal areas, buttock,
leg, lower back
Trigger point and Tinel sign by palpation the SNR
Bladder hypersensitivity
In neurogenic lesions: detrusor hypotonia