Introduction

Vulvar pain is a symptom that was described in the literature as early as the first century AD, by Soranus of Ephesus when he wrote about “Satyriasis in females” [1]. Few publications referred to this type of pain until 1987, when Friedrich described vulvar vestibulitis syndrome as “severe pain on vestibular touch or vaginal entry” [2]. Subsequently, there was little advancement in the classification of chronic vulvar pain trough the 1990s. However, in 2003, the International Society for the Study of Vulvovaginal Diseases (ISSVD) recommended that vulvodynia be defined as chronic vulvar pain occurring for at least 3 months [3]. Additionally, the ISSVD indicated that vulvodynia can be further characterized by location (generalized or localized to the vaginal entrance or clitoris), by whether the pain is provoked by contact or unprovoked, by onset (primary from first genital contact or secondary if it occurred after a pain-free period), and by whether the pain is intermittent or persistent [4]. After recognizing that vulvodynia is a condition experienced by millions of women, the National Institutes of Health convened consensus meetings on the state of vulvodynia research in 2004 and 2011 [5, 6]. These consensus meetings, and subsequent research, suggested that vulvodynia is a heterogeneous disorder and the 2003 diagnostic criteria did not sufficiently describe the spectrum of disease. Therefore, in 2015 the ISSVD, the International Society for the Study of Women’s Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS) developed new consensus terminology for the classification of persistent vulvar pain [7].

Currently, vulvar pain can be classified as (1) pain caused by a specific disorder, that is, acute or chronic pain with an identifiable cause such as vaginal infections, neoplasms, or neurological disorders; and (2) vulvodynia, which is defined as chronic pain, lasting 3 months or longer without an identifiable cause [7]. Vulvodynia may may be further subtyped based on location, onset, timing, and provocation. Additionally, it is important to note that in this new classification, vulvodynia may also coexist with other disorders such as pelvic floor muscle dysfunction, specific skin disorders such as lichen sclerosus; other comorbid pain syndromes such as interstitial cystitis/bladder pain syndrome (IC/BPS) or irritable bowel syndrome (IBS); and emotional distress such as anxiety, depression, and poor coping [7]. In addition to psychiatric, musculoskeletal, neurological, and inflammatory factors, vulvodynia severity may also be impacted by hormonal, genetic, and environmental factors that are poorly understood [8].

Epidemiology and Burden of Disease

It is estimated that by age 40, 7%–8% of women experience vulvar pain consistent with vulvodynia, making the lifetime prevalence of vulvodynia among women 18–64 years of age approximately 16% [11]. Hispanics are 1.4 times more likely to develop vulvar pain symptoms compared to white women [12]. Research shows that most women who are able to access care self-identify as white (and are educated and employed). Hispanic women are underrepresented in clinical and research settings, suggesting that for nonwhites there may be a significant disparity in access to care and inclusion in research [13, 14].

The burden of this disease on women, their partners, families, and communities has been extensively studied and research consistently shows that this disorder can have devastating effects. Women with vulvodynia suffer significant distress and poor quality of life. More than 50% of women experience pain with intercourse and more than 80% fear intercourse or report disabling sexual dysfunction [15]. Women with vulvodynia also tend to have higher somatic awareness, environmental stress, catastrophizing, and psychological distress when compared to pain-free controls [14]. Vulvodynia is four times more likely in women with a mood or anxiety disorder, and women with vulvodynia are seven times more likely to develop a new mood or anxiety disorder [16]. Thus far, it is not yet clear whether psychological symptoms promote the development of vulvodynia, or they develop mostly as a consequence of being in chronic pain.

Research also shows a significant overlap between vulvodynia and other chronic pain conditions such as IBS, IC/BPS, fibromyalgia, chronic fatigue syndrome, migraines, and temporomandibular joint disorders (TMD) [14]. Approximately 20% of vulvodynia patients report being additionally diagnosed with one or more of these disorders [14] and the odds of screening positive for vulvodynia are to three times higher in women who report having IC/BPS, IBS, fibromyalgia, or TMD [17, 18]. Although we do not know with certainty whether the presence of other chronic pain syndromes promotes the development of vulvodynia, the evidence suggests that vulvodynia patients with fewer comorbid pain conditions have a greater chance of responding successfully to treatment [19, 20].

The costs to the US healthcare system have also been studied. A 2012 study reported that a patients with vulvodynia has an average of 8.8 office visits/year [21]. Researchers calculated an annual cost of $17,724.80 per patient with vulvodynia, which converts to an estimated annual national expenditure that ranges from $31 billion to $72 billion (higher than the estimated cost for endometriosis, fibromyalgia, and IC/BPS combined) [21].

Despite the immense burden of disease and personal distress reported by patients, almost 50% of patient never seek care [12]. Of those who seek treatment, 41% see three or more doctors before receiving a diagnosis [12]. On average, women suffer with pain for 2–5 years and fewer than 50% receive a diagnosis. It is estimated that even after being diagnosed with a chronic pain syndrome, fewer than 1.5% of women receive an actual diagnosis of vulvodynia [12, 22]. Anecdotal patient reports and multiple studies confirm that women are not only impacted by the pain, which causes them suffering and distress, but they are also negatively affected by feelings of social isolation and dismissive or invalidating attitudes from their healthcare providers [23, 24].

Anatomy of Vulvar Pain

Anatomically the vulva is the region extending inferiorly from the pubic arch and the inguinal and femoral creases to the perineal body (Figure 12.1). Important anatomical structures within this area include the mons pubis, labia majora, labia minora, clitoris, and clitoral bulbs and the vestibule (Figure 12.1) [25]. Although vulvodynia can be described as pain in any of these areas, the terms vestibulitis, vulvar vestibulitis syndrome, focal vulvitis, vestibular adenitis, and provoked vestibulodynia (PVD) are used to describe a subtype of vulvodynia in which the pain is localized only to the vulvar vestibule and provoked by contact [8]. By contrast, the terms generalized vulvodynia, essential or dysesthetic vulvodynia, and burning vulva syndrome are used to describe a subtype where the pain is unprovoked, diffuse, and affects the entire vulva [8]. The neural distribution for the vulvar area is complex, ts innervation originates from branches of the iliohypogastric, ilioinguinal, genitofemoral, pudendal, posterior femoral cutaneous, and cluneal nerves which in turn arise from the lumbar and sacral plexuses (Table 12.3, Figure 12.1).

Figure 12.1 Anatomy and neurological distribution of the vulvar innervation.

Vulvar pain can result from damage, inflammation, or entrapment of any of these nerves resulting in a complexity of overlapping pain dermatomes (Figure 12.2). Patients may present with local or generalized pain, and both subtypes may present with spontaneous or provoked pain. At this point it is not clear whether provoked, unprovoked, localized, or generalized vulvar pain has overlapping or distinct pathophysiology. Additionally, because of this anatomical location, women with vulvar pain may experience symptoms not only with intercourse but also with daily activities such as sitting and walking.

Figure 12.2 Vulvar dermatomes.

Pathophysiology

Vulvodynia is characterized by chronic vulvar or vaginal pain that is often described by patients as burning, stinging, irritation, or rawness [4, 8]. Vaginal mucosa changes, neuronal proliferation and hyperactivity, central nervous system processing abnormalities, muscular dysfunction, heightened inflammatory response, psychological conditions, and genetic polymorphisms are all thought to play a role in the development, maintenance, and progression of pain [26, 27].

Hypersensitivity of the vulvar vestibule is one of the defining characteristics of vulvodynia (especially PVD); however, the mechanisms for this hypersensitivity are not well understood. Studies show that women with localized vulvodynia exhibit abnormally low sensory thresholds and increased nerve fiber proliferation (particularly hyperexcitable nociceptors) in vestibular tissue resulting in allodynia (painful response to a nonpainful stimulus such as light touch with a cotton-swab) and peripheral sensitization [26, 28–32]. Interestingly, this increased pain sensitivity is also present at nongenital sites (e.g., forearm), suggesting that these women may also experience central nervous system sensitization (central sensitization), perhaps explaining the high prevalence of comorbid nongenital pain syndromes, such as IBS, PBS, and fibromyalgia, found in vulvodynia patients [14, 32]. The concept of central sensitization playing a role in vulvodynia is additionally supported by several functional and structural brain imaging studies showing that women with a particular subtype of vulvodynia, PVD, demonstrate augmented neural activity in areas of the brain associated with increased perception to nonpainful and painful stimulation of the vestibule [33]. Other imaging studies confirm heightened activation in areas of the brain involved in pain processing and changes in gray matter density in women with PVD compared to controls [32, 34]. Together, these findings are interpreted by scientists as evidence that augmented sensory processing [32] is an important pathophysiological process in vulvodynia.

Periodic swelling and erythema of the vestibule and vulva is another symptom commonly described by vulvodynia patients. Generally, erythema is recognized as an indicator of an underlying infectious process; however, in vulvodynia, erythema is not a reliable diagnostic marker for the presence of infection. Once acute infectious processes are ruled out, persistent erythema is thought to occur due to a persistent neuroinflammatory response, whereby an exaggerated inflammatory response, characterized by excess release of proinflammatory cytokines (e.g., interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α), leads proliferation of nociceptive fibers with lower thresholds, ensuing in pain and a process known as neurogenic inflammation [26, 35]. Histological studies show that evidence of neurogenic inflammation is not consistently identified in all cases of vulvodynia, leading researchers to question whether vulvodynia is an inflammatory condition at all [32].

Scientists speculate that the proinflammatory and hyperactive neuroendocrine histological markers found in women with chronic vulvar pain may be linked to specific genetic polymorphisms. To date, no single genetic marker for vulvodynia has been identified; however, genetic studies are focusing on (1) polymorphisms that increase the risks of candidiasis or other infections, (2) polymorphisms for an exaggerated inflammatory response, and (3) genetic markers for increased susceptibility to hormonal changes caused by oral contraceptives [32].

Although the role of hormones is well understood in the postmenopausal state, where hypoestrogenism is known to lead to vaginal atrophy and pain, the role of hormones and altered estrogen receptor function in promoting neurogenic inflammation or sensory abnormalities in premenopausal women is less well understood. Initial histological studies in reproductive aged women with vulvodynia identified vaginal samples containing “skip lesions” that lack estrogen receptors [36]. Other studies suggest that decreasing serum estradiol levels associated with use of oral combined hormonal contraceptives (CHCs) may lead to decreases in mechanical pain thresholds [32]. However, although some case-controlled studies suggest a link between CHCs and developing vulvodynia, this finding has not been consistently replicated in larger population based prospective studies [32].

Pelvic floor muscle dysfunction and pain are commonly found in women with vulvodynia; when using reliable methodology for examining the vaginal musculature, more than 90% of women enrolled in the National Vulvodynia Registry (NVR) had abnormal muscular exams [9]. Women with vulvodynia are reported to have lower pelvic muscle pressure pain thresholds, increased resting tone, impaired voluntary relaxation, and decreased voluntary muscle contractility [27]. In general, vulvodynia is associated with pelvic floor muscle overactivity and weakness. Chronic changes in muscle tissue can lead to hypoxia and perhaps neurogenic inflammation that can manifest as itching, burning, tingling, cold, or sharp and shooting pain in the vulvar and/or vaginal areas [32]. Changes in the biomechanics of the pelvic musculature can result from events such as acute infection, vaginal childbirth, and abdominal and pelvic surgery; thus in some cases, vulvodynia can result from deficiencies in the pelvic musculature that are due to a previous traumatic event [32]. In other cases, the muscular dysfunction is thought to be a secondary process, that is, the muscular dysfunction develops secondary to chronic mucosal inflammation and vulvar pain [37].

The brief review provided previously does not cover the extent of all vulvodynia research. Although the exact pathophysiology of vulvodynia is not yet understood, there is little doubt that it may involve multiple processes , that is, that women may develop the symptom of chronic vulvar pain via different mechanisms. Additionally, psychosocial factors such as depression, anxiety, physical and sexual abuse, sexual dysfunction, and partner and relationship influences have all been implicated in the development and maintenance of vulvar pain [32]. Hence a multifactorial/multidisciplinary approach is key to the diagnosis and treatment of this condition [7].

Clinical Presentation

Often the pain experienced by women is described as burning, stabbing, shooting pain, in the vulvar or vaginal area [4, 8]. Patients may also present with complaints of itching or a chronic (noninfectious) discharge. Although erythema and discharge may be present, it is important to remember that in vulvodynia, these symptoms are not reliably associated with infectious causes, despite studies suggesting that recurrent yeast infections and specially Candida albicans may predispose women to developing vulvodynia [27, 32].

The pain can be described as localized to a specific area or generalized; among women enrolled in the NVR, 10% presented with generalized vulvar pain and 90% presented with pain localized to the vestibule [9]. Pain during touch or intercourse (provoked pain) is reported by most women who are sexually active and some continue to be sexually active despite being in pain [9]. As previously stated, a substantial proportion of patients have signs of pelvic floor muscle dysfunction that often manifests as dyspareunia [14]. Approximately 20% of women will report comorbid pain conditions such as IBS, PBS, migraines, TMD, fibromyalgia, and chronic pelvic pain [9, 15] and nearly 40% will present with signs of distress such as anxiety, depression, and sexual dysfunction [9, 14]. Sometimes women are able to identify a specific trigger such as trauma (including surgical interventions), vaginal childbirth, recurrent vaginal or bladder infections, hormonal changes, and oral contraceptive use; however, in many of cases a specific trigger is not clearly identified [32].

Clinical Evaluation

Vulvodynia is a chronic pain syndrome; therefore, an extensive biopsychosocial assessment that begins with a history and physical exam is crucial to determining the source and impact of the pain [38]. The widespread impact and the high proportion of women who do not seek care emphasizes the need for screening, especially for women who present with other chronic pain syndromes [14]. Although validated screening questionnaires are available [22], screening can be easily done by asking women whether they experience pain with activities such as sitting, walking, or intercourse. Many women report being invalidated and dismissed [23, 39] by providers, family, and peers. Therefore, after screening, the next step in the evaluation should include establishing rapport and trust through validation of the patient’s symptoms. In addition, it is important to remember that many women will not discuss symptoms related to sexuality or sexual pain, until they feel they can trust their healthcare provider. Overall, the goal of the initial (and subsequent) medical interviews should be to (1) validate the patient’s symptoms, (2) gather relevant medical history that may help identify causes of pain, and (3) provide education and reassurance [13].

Classically vulvodynia has been described as a diagnosis of exclusion where clinicians are taught to first determine if there is an obvious cause for the pain. This task can be overwhelming because comorbidities that may cause (or have been associated with) vulvodynia include vulvar/vaginal infection such as recurrent yeast or bacterial vaginosis, inflammation from vulvar dermatoses such as lichen sclerosus; neoplasm; trauma from life events such as childbirth; trauma from sexual abuse; iatrogenic trauma such as surgery; hormonal deficiencies that may or may not be associated with vaginal atrophy; neuropathies such as pudendal neuralgia, pelvic floor muscle dysfunction; structural defects; visceral pain syndromes such as IBS, PBS, and endometriosis, and psychosocial factors such as anxiety and sexual dysfunction [13, 14]. At minimum, a detailed history should review (1) a general medical, surgical, and obstetrical history; (2) pain characteristics (location, duration, exacerbating factors); (3) associated symptoms such as bowel, bladder, or musculoskeletal symptoms; (4) sexual behavior and sexuality; (5) psychological history; (6) comorbid medical problems; (7) previous treatments; and (8) physical or sexual abuse [13]. Before considering lengthy differential diagnoses, it may be more efficient for providers to categorize the patient’s symptoms by organ systems, that is, urological, gastroenterological, reproductive, musculoskeletal, neurological, psychiatric. It is also important to note that this type of extensive history taking may require more than the time allotted to the first visit. Moreover, some patients may not disclose some information until they feel they can trust the provider; thus important elements of the history may not become evident until subsequent visits. Validated questionnaires such as the Female Sexual Function Index (FSFI), the McGill Pain Questionnaire (MPQ), or the PROMIS® vulvar discomfort scales, are more helpful than asking patients to rate their pain from 0 to 10 and allow patients to provide self-reported pain measures that give clinicians a better understanding of the quality, intensity, and impact of the pain on daily activities and quality of life. In addition, questionnaires are efficient and allow providers to collect a large amount of information in the limited clinical time available for face-to-face interaction [13].

Questions about the quality of pain, location, radiation pattern, intensity, factors that improve symptoms or worsen symptoms, and therapies tried previously and their impact on symptoms are essential and should be included in the history taking process. When painful intercourse is reported as a symptom, providers should clarify if the discomfort is perceived either upon entry or deep penetration, or both. The use of a pain map is useful to localize the pain and research has shown that patients with multiple pain areas (generalized pain) are more likely to exhibit signs of central sensitization [40], which has been associated with the need for multidisciplinary treatments [41]. Women may also use pain descriptors such as burning, stinging, hotness, rawness, and irritation, which have been associated with neuropathic pain [42]. Identifying such descriptors in combination with a specific neuralgia could lead the clinician to investigate a neuropathy as a cause of symptoms.

Research confirms that women want information about the examination process before, during, and after the physical evaluation [43]. Experts recommend the physical inspection start by first educating the patient about the examination; the anatomy that will be examined; and the reasons for performing the assessment, that is, what information will be obtained during the examination [8, 39, 44]. A strategy used to minimize anxiety and discomfort during the examination is the interactive educational pelvic examination, which includes (1) explanations to the patient while performing the assessment, (2) describing the specific actions during each step, and (3) using a mirror to enable the patient to visualize her anatomy and the examination [8, 45]. This allows the clinician to thoroughly evaluate the patient’s pain, exclude diagnoses, educate the patient regarding normal anatomy and sexual function, and reassure the patient when no pathology is uncovered [46, 47].

In women with vulvodynia, the physical examination starts with a general assessment of the patient’s mood, affect, and musculoskeletal status before proceeding to the pelvic evaluation. The nongenital musculoskeletal examination includes evaluation of the patient’s gait; posture in standing and sitting positions; palpation of the back, abdominal, gluteal, and upper lower extremity muscles; palpation of the sacroiliac joints; and assessment of muscle strength, range of motion, sensation and reflexes. Palpation of these areas can identify areas of pain, hypercontractility, and instability [48].

The next step, the pelvic examination, begins with an external inspection of the vulvar and perineal areas to identify lesions, scars, or signs of trauma; dermatological changes; or signs of infection such as discharge. Vestibular erythema may be present; however, as previously stated, this is not consistently found in women with vulvodynia, and often, the external examination is normal. After visual inspection, providers should perform a neurosensory evaluation to identify areas of allodynia, a painful response to a nonpainful stimulation, such as light touch with the cotton end of a cotton-tipped applicator, or hyperalgesia, an excessively painful response to a painful stimulus such as the wooden end of a cotton-tipped applicator. Unilateral or bilateral allodynia and/or hyperalgesia in the S2–S4 neuronal distribution of the vulva and perineum, or absence of an anal wink reflex, may be indicators of neuropathies such as pudendal neuralgia that can also present as vulvodynia [49, 50]. Neuropathic pain can also be identified in nongenital areas, such as the abdomen and lower back, by using similar testing to identify allodynia and hyperalgesia. Neuropathies should be suspected in patients presenting with (1) pain that radiates along a particular dermatomal distribution and (2) risk factors such as a history of surgical interventions, trauma, childbirth, and repetitive activities such as long-distance cycling or prolonged sitting [51, 52].

Vulvodynia can also be characterized with a neurosensory exam of the vestibular area. The cotton swab test is performed by applying gentle pressure to six anatomical sites on the vestibule using the face of a clock for reference, where 12 o’clock and 6 o’clock correspond to the midline just below the urethra and midline at the level of the posterior fourchette that is just above the anus (Figure 12.3). This type of neurosensory testing can help localize areas of tenderness and distinguish localized from generalized pain. Branches of the ilioinguinal, iliohypogastric, and pudendal nerves all contribute to the sensory innervation of the vulva; thus the cotton-tipped evaluation can also identify neuropathies in these corresponding dermatomal distributions.

Figure 12.3 Sensory examination of the vestibule to identify vestibular allodynia.

After inspection of the perineum, a single-digit examination can be used to assess the pelvic floor muscles for strength, tone, and pain. The internal musculoskeletal single-digit examination is the most reliable method for assessing pelvic muscle tenderness [48]. To perform this part of the examination, the examiner can gently and slowly insert a lubricated digit into the vagina and ask the patient to squeeze and relax around the digit. Next, the examiner can palpate the levator ani, piriformis, obturator, and coccygeus muscles by applying deep palpation to the lateral, anterior, and posterior vaginal walls. The Valliex’s sign can be done by pressing medial to the ischial spine bilaterally, in order to stimulate the pudendal nerve at the point of nerve injury and identify radiation of pain or paresthesia along the course of the nerve [8]. Tenderness, high tone, and involuntary spasm with mild or moderate palpation of the muscles of the vaginal introitus and the pelvic floor is abnormal; pelvic floor muscles can normally tolerate as much as 2 kilograms of pressure without pain. Pain elicited during this portion of the examination can be indicative of myalgias and pelvic floor muscle dysfunction.

Cotton-tipped examination of the vestibule and the single-digit examination are considered essential to the diagnosis of vulvodynia; however, studies show there is little correspondence between higher levels of pain during daily activities such as intercourse and what providers can replicate with the cotton-tipped applicator test or the single-digit examination [13]. In fact, patients may demonstrate improvements in pain during clinical evaluation without demonstrable improvement in pain or function outside clinical settings. In such cases, the “gold-standard” cotton-tipped test may underestimate the degree of pain and distress experienced by women in their daily lives [13] and it is recommended that providers follow patient reported outcomes instead.

If the patient can tolerate a single-digit muscular assessment, a bimanual evaluation of the uterus and adnexa can be completed before proceeding to the speculum examination. The speculum may cause extreme discomfort in patients with vulvodynia, as such it should be performed using lubrication and slow insertion that avoids touching the urethra or pinching the cervix. At this time, vaginal culture and swabs can be collected to rule out infections and dysplasia. For patients who cannot tolerate single-digit examination the speculum examination may be postponed to subsequent visits after treatment is initiated, unless concerning symptoms such as bleeding or discharge are reported by the patient.

The diagnosis of vulvodynia is based primarily on patient symptoms and clinical examination, including findings of the cotton swab test [53–56]. Additional diagnostic tests such as urinalysis, pelvic ultrasound, or CT scan are not necessary unless patients present with urinary or GI symptoms, pelvic pain, pelvic mass identified on examination, and bleeding abnormalities.