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Generalized Vulvodynia
Introduction:
A common subtype of vulvodynia is provoked vestibulodynia (PVD), characterized by severe pain upon contact to the vaginal entrance. Some researchers have further delineated the PVD group based on pain onset (primary vs secondary PVD, referred to as PVD1 and PVD2, respectively).
Aim:
This study aims to review available evidence regarding sociodemographic variables, pain characteristics, medical history and examination findings, quantitative sensory testing, genetic markers, psychosocial/sexual/relationship function, treatment outcome, and brain imaging in women with PVD1 and PVD2.
Methods:
All available data related to PVD1 and PVD2 were reviewed.
Main outcome measures:
There is mixed evidence supporting the assumption that women with PVD1 fare worse on all variables investigated.
Results:
The review indicated that although women with PVD1 seem to fare worse on many variables examined (eg, pain severity, genetic markers), many studies also indicated no significant group differences or-less commonly-that women with PVD2 fare worse on some variables (eg, sexual function).
Conclusion:
Although it has been suggested that different pathophysiologic processes are involved in the development and maintenance of PVD1 and PVD2, the data reviewed were mixed. While most studies indicated that women with PVD1 have higher pain intensity, higher sensitivity, more genetic influence, more evidence of inflammation, lower successful treatment outcomes, and different neural activation patterns and structural findings, these results were not consistently reported. In addition, the data for subgroup differences in psychosocial, sexual, and relationship variables were not convincing. A more precise definition of primary and secondary PVD is needed, and importantly, prospective, longitudinal studies are essential for clarifying any differences within these PVD subgroups.
According to the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; American Psychiatric Association [APA], 2000), sexual dysfunctions are characterized by disturbances in the psychophysiological
processes that characterize the sexual response cycle or by pain associated with sexual intercourse. The sexual response cycle,
as defined by the DSM-IV-TR, is divided into four phases: (1) desire, which consists of fantasies about and the wish to have
sexual activity; (2) excitement, which manifests as a subjective sense of sexual pleasure and associated physiological changes
(e.g., vaginal lubrication and expansion in females, penile tumescence and erection in males); (3) orgasm, which reflects
the peak of sexual activity and consists of the release of sexual tension and the rhythmic contraction of the perineal/anal
sphincter muscles and reproductive organs; and (4) resolution, which indicates a sense of muscular relaxation and general
well-being.
The first three stages of the sexual response cycle (desire, excitement, and orgasm) form the basis for most of the sexual
dysfunctions as defined by the DSM-IV-TR. Although there are no dysfunctions associated with the resolution phase, the sexual
pain disorders category contains a description of two disorders that can potentially interfere with sexual functioning in
general. Clinically, it is apparent that there is a high comorbidity among the sexual dysfunctions such that a problem at
any one stage of the sexual response cycle is likely to lead to difficulties with other stages. For example, a patient presenting
with erectile difficulties may also experience problems with orgasm and desire. However, sound empirical data on comorbidities
are lacking (Meana, Binik, & Thaler, 2008). The DSM-IV-TR states that when more than one sexual dysfunction is present, all
should be recorded (APA, 2000).
OBJECTIVE: To assess the effectiveness of nightly application of 5% lidocaine ointment for treatment of vulvar vestibulitis. METHODS: Over 17 months, we assessed women presenting to our pain clinic for evaluation of introital pain; 61 women met the criteria for vulvar vestibulitis and participated in a treatment trial. We measured daily pain and intercourse-related pain using a 100-mm visual analog scale. We compared ability to have intercourse and pain ratings before and after treatment, and investigated whether prior treatment or gynecologic comorbidities predicted response to treatment. RESULTS: After a mean of 7 weeks of nightly treatment, 76% of women reported ability to have intercourse, compared with 36% before treatment (P = .002). Intercourse-related pain score was 39.11 (95% confidence interval [CI] 30.39, 47.83) points lower after treatment (P < .001), with a decrease of 10.37 (95% CI 3.53, 17.21) points in daily pain score (P = .004). We found no association between response to prior episodic use of lidocaine and response to nightly therapy with lidocaine ointment. Few patient characteristics predicted response to treatment; however, women with interstitial cystitis and other vulvar conditions were least likely to benefit. CONCLUSION: Long-term, nightly application of 5% lidocaine ointment shows promise as a treatment for management of vulvar vestibulitis; a randomized, double-blind, clinical trial is warranted.
To estimate the prevalence of unexplained chronic vulvar pain (burning or sharp knife like pain or pain on contact) in an ethnically diverse population-based sample of women.
We used town census directories to identify 4915 women age 18 to 64 from 5 ethnically diverse Boston communities and asked them to complete a self-administered questionnaire pertaining to current and past chronic lower genital tract discomfort (response rate 68%). We calculated the cumulative incidence and 95% confidence intervals by demographic and reproductive characteristics. Approximately 16% of respondents reported histories of chronic burning, knife like pain, or pain on contact that lasted for at least 3 months or longer, and nearly 7% were experiencing the problem at the time of the survey. Chronic vulvar pain on contact decreased with increasing age, but the cumulative incidence of chronic burning and knife like pain was similar across all ages. Contrary to earlier clinical assessments, white and African American women reported similar lifetime prevalences. However, Hispanic women were 80% more likely to experience chronic vulvar pain than were white and African American women. Women with histories of chronic vulvar pain were 7 to 8 times more likely to report difficulty and great pain with their first tampon use than were women without such histories. Nearly 40% of women chose not to seek treatment, and of those who did, 60% saw 3 or more doctors, many of whom could not provide a diagnosis.
Chronic unexplained vulvar pain is a highly prevalent disorder that is often misdiagnosed.
Vulvar pain occurring in the absence of an underlying recognizable disease has become an increasingly common clinical problem. Members of the International Society for the Study of Vulvovaginal Disease (ISSVD) astutely recognized this idiopathic vulvar pain as a unique entity in 1976 and, at that time, used the term burning vulva syndrome to identify it. Subsequently, the ISSVD renamed the disorder vulvodynia and suggested that two clinically distinctive subsets, dysesthetic vulvodynia and vestibulitis, might exist. However, recent studies have failed to confirm an inflammatory pathogenesis for vestibulitis, and in 1999 that term was deleted from the ISSVD classification. In 2003, at the 17th World Congress, the ISSVD reestablished vulvodynia as the preferred term for vulvar pain occurring in the absence of an underlying recognizable disease and, from a standpoint of classification, identified generalized and localized subsets. The ISSVD further noted that in either subset, pain could occur spontaneously and/or could develop as a result of physical provocation. The purpose of this recommended nosology is to further communication among the various specialties that care for women with vulvodynia and to assist in the formulation of studies regarding the pathophysiology and treatment of the disorder.
Researchers have failed to find a consistent association between childhood victimization and vulvodynia, a debilitating, unexplained vulvar pain condition. However, selection bias associated with case ascertainment, and differential reporting bias between clinic-based cases and controls, may explain in part the inconsistent findings. In 2000-2003, the authors identified 125 women experiencing symptoms of vulvar pain consistent with vulvodynia and 125 age- and community-matched controls from the Boston, Massachusetts-area general population. Telephone-administered questionnaires were used to obtain medical, psychiatric, and reproductive histories. Self-administered surveys assessed childhood exposure (age <12 years) to physical and sexual abuse and to poor family support. After author adjustment for socioeconomic position, women with vulvar pain versus controls were 2.6 times more likely to report never/rarely receiving childhood family support, such as comfort, encouragement, and love (95% confidence interval (CI): 1.3, 5.1). Adult-onset vulvodynia was strongly associated with abuse as a child more than a few times physically (odds ratio (OR) = 4.1, 95% CI: 1.7, 10.0) or sexually (OR = 6.5, 95% CI: 1.2, 35.1). When abused women were compared with those with no history of abuse, the association was largely confined to those harmed by a primary family member (OR = 3.6, 95% CI: 1.6, 8.0 for physical abuse; OR = 4.4, 95% CI: 0.9, 22.9 for sexual abuse). Additional population-based studies of clinically confirmed cases of vulvodynia are needed to replicate this association.
Clinically, botulinum toxin A blocks the cholinergic innervation of the target tissue. Recently, it has been proved effective not only at a neuromuscular junction but also within parasympathetic or sympathetic neural synapses. Seven women with pain on genitalia that could not be controlled with conventional pain managements were enrolled in this study. Twenty to 40 U of botulinum toxin A were used in each injection. Injection sites were the vestibule, levator ani muscle or the perineal body. Repeat injections were administered every 2 weeks if the patient's symptoms had not fully subsided. In all patients, pain had disappeared with botulinum toxin A injections. Five patients needed to be injected twice; the other two patients needed only one injection. We did not observe complications related to botulinum toxin A injections, such as pain, hemorrhage, infection, muscle paralysis or other complications. The subjective pain score improved from 8.3 to 1.4, and no one has experienced a recurrence (the follow-up period was four to 24 months, with a mean follow-up of 11.6 months). Botulinum toxin A is effective in blocking nociception. Even though further investigation and well-controlled study will be necessary, we suggest that the botulinum toxin therapy would be useful and safe in managing vulvodynia of muscular or neuroinflammatory origins.
Fibromyalgia is a chronic pain disorder of which other clinical features, such as persistent fatigue and disordered sleep, may be a secondary consequence. The initial pharmacological approach to treating the disorder is the management of the pain. Tricyclic antidepressants are the most effective drugs in use so far, especially when administered in combination with other therapies (e.g., selective serotonin re-uptake inhibitors), which suggests modulation of the neurotransmitters serotonin and noradrenaline. The effectiveness of amitriptyline and related tricyclic antidepressants, however, is consistent with the involvement of mechanisms, such as potassium channel modulation and NMDA receptor antagonism, in addition to or in place of the modulation of monoamine neurotransmitters. Investigation of the importance of each of the pharmacological properties of amitriptyline and related molecules in the management of fibromyalgia could provide clues for the rational design of new drugs.
Vulvar pain occurring in the absence of an underlying recognizable disease has become an increasingly common clinical problem. Members of the International Society for the Study of Vulvovaginal Disease (ISSVD) astutely recognized this idiopathic vulvar pain as a unique entity in 1976 and, at that time, used the term burning vulva syndrome to identify it. Subsequently, the ISSVD renamed the disorder vulvodynia and suggested that two clinically distinctive subsets, dysesthetic vulvodynia and vestibulitis, might exist. However, recent studies have failed to confirm an inflammatory pathogenesis for vestibulitis, and in 1999 that term was deleted from the ISSVD classification. In 2003, at the 17th World Congress, the ISSVD reestablished vulvodynia as the preferred term for vulvae pain occurring in the absence of an underlying recognizable disease and, from a standpoint of classification, identified generalized and localized subsets. The ISSVD further noted that in either subset, pain could occur spontaneously and/or could develop as a result of physical provocation. The purpose of this recommended nosology is to further communication among the various specialties that care for women with vulvodynia and to assist in the formulation of studies regarding the pathophysiology and treatment of the disorder.
Vulvodynia, or chronic vulvar pain, which often is accompanied by dyspareunia, is quite prevalent and difficult to treat effectively. Neuropathic pain typically is described, and findings that sensitization to pain is increased at sites removed from the vulva suggest that systemic treatment for nerve hypersensitivity might prove helpful. Today antidepressants, especially tricyclic antidepressants (TCAs) such as amitriptyline, are commonly used in low dosage to treat vulvodynia. This retrospective study included 271 affected women, 209 of whom were initially treated with a TCA. Amitriptyline was administered to 183 women, while smaller numbers received desipramine or other TCAs. A total of 162 women, including 122 started on a TCA, were followed up for a median time of 3.2 months. The typical starting TCA dose was 25 mg each night (or 10 mg for elderly patients), and the maximum nightly dose was 225 mg. Patients rated their pain on a 0-to-10 scale. Localized pain was somewhat more frequent than generalized vulvar pain in these women, whose average age was 37 years and who had experienced pain for nearly 5 years on average. During a median follow-up of 3.2 months, 59% of women who had taken a TCA improved by more than 50%, compared with 38% of those not taking a TCA at follow-up; the odds ratio (OR) was 2.35, with a 95% confidence interval (CI) of 1.23–4.42. Multivariate analysis showed that taking a TCA at the first follow-up assessment correlated strongly with improvement (OR, 4.23; 95% CI, 1.98–9.01). Among the factors not associated with the outcome were age, severity of pain, localized versus generalized vulvar pain, duration of untreated pain, age at menarche, oral contraceptive use, and the number of previous pregnancies. A repeat analysis limited to women taking amitriptyline yielded similar results. Of 51 women not taking any antidepressant or anticonvulsant drug when followed up, one-third reported improvement. Most women with vulvodynia who take TCAs in general, or amitriptyline in particular, tolerate the medication and are likelier than other affected women to report at least 50% improvement at follow-up. Randomized controlled trials comparing TCAs with other treatments are needed.
Botulinum toxin A is the newest therapy for the treatment of a variety of medical disorders caused by abnormalities of muscle activity. After successful use in other medical subspecialties, the newest applications of this potent neurotoxin are within the lower urinary tract. The toxin has evolved from a cause of fatal disease into the newest neuropharmacologic medical therapy.
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The purpose of this study was to assess the prevalence and type of psychological distress in women with vulvar vestibulitis syndrome (VVS). A retrospective chart review was conducted of all women receiving a diagnosis of VVS referred to a tertiary care facility during a two-year period. Brief psychological questionnaires, including the Personality Assessment Screener, Fear of Negative Evaluation Scale, Golombok-Rust Inventory of Sexual Satisfaction, and the Phobia Rating Scale were administered. Fifty-consecutive cases were reviewed along with 12-15 month follow-up data for 41 cases. Phobic anxiety to vaginal touch or entry was significantly higher in women with VVS than normative data. Fear of Negative Evaluation was a strong associated feature, and for 30% approached clinically significant levels. Twenty-six percent showed a moderate, while another 26% showed a mild clinically distressed profile. Negative affect and social withdrawal were among the most frequently endorsed variables. Improvement in allodynia and intercourse were both related to these psychological variables, and a multiple regression analysis supported the use of psychological instruments in addition to standard medical assessment. A subgroup of women with VVS display clinically significant broad based psychological distress that warrants additional assessment. The use of psychological questionnaires in addition to medical assessment of women with VVS may provide valuable information predictive of treatment needs and response.
We call attention to a group of patients with chronic vulvar burning (vulvodynia), who do not have apparent infections or easily discernible abnormal physical findings, but who on simple sensory testing have allodynia, hyperalgesia, hyperpathia, and hypoesthesia in varying permutations within the areas innervated by the pudendal nerve. We propose that pudendal neuralgia (pain along the pudendal nerve) is one of the causes of idiopathic vulvodynia. In those patients in whom a neurologic, metabolic, infectious, traumatic, or malignant cause for neuralgia is not found, medical management with tricyclic antidepressants, antiepileptic agents, or both may prove helpful. Awareness of this entity will lead to earlier diagnosis, treatment, and reassurance of patients with chronic vulvar burning.
Thirty-three women diagnosed as suffering from vulvar vestibulitis syndrome, marked by a significant history of long-term moderate to severe chronic introital dyspareunia and tenderness of the vulvar vestibule, were selected for treatment. Patients were given a computerized electromyographic evaluation of the pelvic floor muscles and were then provided with portable electromyographic biofeedback instrumentation and instructions on the conduct of daily, at-home, biofeedback-assisted pelvic floor muscle rehabilitation exercises. They received intermittent evaluations of pelvic floor muscles to ensure compliance and monitor their progress and symptom changes. The results show that after an average of 16 weeks of practice, pelvic floor muscle contractions increased 95.4%, resting tension levels decreased 68%, and the instability of the muscle at rest decreased by 62%. Subjective reports of pain decreased an average of 83%. Twenty-eight patients had abstained from intercourse for an average of 13 months. Twenty-two of these 28 patients resumed intercourse by the end of the treatment period. Six month follow-up indicated maintenance of therapeutic benefits.
Our anatomic findings have led us to define conflictual relations that may be encountered in their course by the pudendal n. and its branches. Starting from the clinical study of a group of patients suffering from chronic perineal pain in the seated position, we have defined, beginning with the cadaver, three possible conflictual settings: in the constriction between the sacrotuberal and sacrospinal ligaments; in the pudendal canal of Alcock; and during the straddling of the falciform process of the sacro-tuberal ligament by the pudendal n. and its branches. Consequently, considering so-called idiopathic perineal pain as an entrapment syndrome, the clinical and neurophysiologic arguments and infiltration tests have led us to define a surgical strategy which has currently given 70% of good results in 170 operated patients. Earlier diagnosis should improve on this.
To compare surface electromyographic (EMG) studies of the pelvic floor in women diagnosed with dysesthetic vulvodynia to those of women with no urologic or gynecologic symptoms.
Fifty women were chosen to participate and placed in one of two diagnostic categories, asymptomatic (no report of urogynecologic abnormalities, n = 25) and those diagnosed with dysesthetic vulvodynia (n = 25). Testing was completed utilizing electromyographic equipment; an inserted, single-user vaginal sensor; and the Glazer protocol. sEMG variables compared were pretest and posttest resting amplitudes, contractile amplitudes, contractile and resting stability, recruitment latency and recovery, and muscle contraction spectral analysis.
The most reliable predictors of symptomatic women were pelvic floor contractile amplitudes of the tonic, phasic and endurance contractions, though 9 of the 15 variables tested proved significant. The phasic (three-second) contractions of the symptomatic group were 46% less than in the pain-free group. Tonic (12-second) contractions were 49% less, and endurance (60-second) contractions proved to be only 47% of those produced by those with no dysfunction.
The results of EMG studies of the pelvic floor in women diagnosed with dysesthetic vulvodynia proved significantly different from those of their urogynecologically asymptomatic cohorts. Physiology of the pelvic floor is an essential piece of knowledge needed to further study the etiology and causative factors in dysesthetic vulvodynia. Though the sample size used in this study was not sufficient to quantify normal pelvic floor function, the study certainly suggests sufficient significant differences between the two groups to merit further study.
To determine the long-term follow-up status of dysesthetic vulvodynia patients who were asymptomatic at the termination of treatment using surface electromyography (sEMG)-assisted pelvic floor muscle rehabilitation.
A chart review of the years 1994-1996 identified 62 patients with a diagnosis of dysesthetic vulvodynia on initial evaluation and who were asymptomatic at the termination of treatment. Forty-three of these patients responded to a survey requesting information on their pain, maintenance activities and treatments, daily functioning and sexual status since treatment termination.
Thirty-eight of the 43 patients (88.4%) reported experiencing no vulvar pain since completion of treatment. Three patients reported a single episode of pain, and two patients reported two episodes each. All five of these patients reported the absence of any vulvar pain for a mean period of 19.8 months prior to completion of the survey. One hundred percent of the 43 dysesthetic vulvodynia patients studied reported being pain free a mean of 39.5 months after successful treatment termination. No vulvar pain-related treatments or significant restrictions on daily activities were reported. All patients reported sexual interest, pleasure and activity.
Surface electromyography-assisted pelvic floor muscle rehabilitation is an effective and long-term cure for dysesthetic vulvodynia.
This study compared group cognitive-behavioral therapy (12-week trial), surface electromyographic biofeedback (12-week trial), and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Subjects were 78 women randomly assigned to one of three treatment conditions and assessed at pretreatment, posttreatment and 6-month follow-up via gynecological examinations, structured interviews and standard questionnaires pertaining to pain (Pain Rating Index and Sensory scale of the McGill Pain Questionnaire, vestibular pain index, pain during intercourse), sexual function (Sexual History Form, frequency of intercourse, Information subscale of the Derogatis Sexual Functioning Inventory), and psychological adjustment (Brief Symptom Inventory). As compared with pretreatment, study completers of all treatment groups reported statistically significant reductions on pain measures at posttreatment and 6-month follow-up, although the vestibulectomy group was significantly more successful than the two other groups. However, the apparent superiority of vestibulectomy needs to be interpreted with caution since seven women who had been assigned to this condition did not go ahead with the intervention. All three groups significantly improved on measures of psychological adjustment and sexual function from pretreatment to 6-month follow-up. Intent-to-treat analysis supported the general pattern of results of analysis by-treatment-received. Findings suggest that women with dyspareunia can benefit from both medical and behavioral interventions.
To examine the prevalence of physical or sexual violence victimization among women referred to a specialty clinic for management of vulvar dysesthesia/vestibulodynia as compared to a healthy gynecology clinic population.
The subjects in this case-control study were women who had completed routine questionnaires prior to presentation to the University of Michigan Center for Vulvar Diseases. Study subjects were all given a diagnosis of vulvar dysesthesia/vestibulodynia. Women without complaints of vulvar pain presenting to a gynecology clinic were enrolled as controls. Information was obtained from the control subjects using a questionnaire similar to the history forms completed by the study group.
Comparisons were made between 242 patients with vulvar dysesthesia/vestibulodynia presenting to a specialty clinic and 113 controls. Cases were more likely to be Caucasian, to be married and to have a higher household income than controls but reported less drug or alcohol abuse and a lower frequency of sexual intercourse. After controlling for possible confounders, no relationship between sexual assault and the presence of vulvar dysesthesia/vestibulitis was found.
The prevalence of victimization was not higher in patients with vulvar dysesthesia/vestibulodynia as compared to the control population after controlling for potential confounding variables.
This article presents data contributed by 428 highly educated, internet-savvy women who frequented various vulvar pain discussion lists. The age range was in the reproductive years and older and over 90% were Caucasians. No country of origin was given. They had a number of distressing symptoms, including vulvar pain at rest and with contact, burning, itching, redness, and inflammation. Most felt that they had either vulvar vestibulitis, vulvodynia, or both, although they had other vulvar conditions as well. Many felt that yeast infections, stress, antibiotics, infections, and chemicals played a contributing role. There were a number of comorbidities, including irritable bowel syndrome, fibromyalgia, and interstitial cystitis. Sexual abuse was not a major issue. The vulvar pain destroyed or altered then sex lives, lowered their self-esteem, and affected their relationships. Often, they relied upon understanding partners, support groups, and hobbies but not the medical profession for comfort.
To assess the effectiveness of nightly application of 5% lidocaine ointment for treatment of vulvar vestibulitis.
Over 17 months, we assessed women presenting to our pain clinic for evaluation of introital pain; 61 women met the criteria for vulvar vestibulitis and participated in a treatment trial. We measured daily pain and intercourse-related pain using a 100-mm visual analog scale. We compared ability to have intercourse and pain ratings before and after treatment, and investigated whether prior treatment or gynecologic comorbidities predicted response to treatment.
After a mean of 7 weeks of nightly treatment, 76% of women reported ability to have intercourse, compared with 36% before treatment (P =.002). Intercourse-related pain score was 39.11 (95% confidence interval [CI] 30.39, 47.83) points lower after treatment (P <.001), with a decrease of 10.37 (95% CI 3.53, 17.21) points in daily pain score (P =.004). We found no association between response to prior episodic use of lidocaine and response to nightly therapy with lidocaine ointment. Few patient characteristics predicted response to treatment; however, women with interstitial cystitis and other vulvar conditions were least likely to benefit.
Long-term, nightly application of 5% lidocaine ointment shows promise as a treatment for management of vulvar vestibulitis; a randomized, double-blind, clinical trial is warranted.
venlafaxine has been available for use as an antidepressant in the United States for a decade.
Comprehensive reviews of venlafaxine have been published elsewhere; thus, this update focuses on newer issues of treatment remission in depression, treatment-resistant depression, and extended-release venlafaxine for generalized anxiety disorder (GAD).
Relevant clinical literature from 1993 through 2003 was identified from database searches of MEDLINE and International Pharmaceutical Abstracts, and from manual searches of reference lists of the identified papers. Search terms included venlafaxine extended-release, venlafaxine XR, treatment-resistant depression, depressive disorders, anxiety disorders, generalized anxiety disorder, and antidepressive agents second generation.
With its dual action of serotonin and noradrenergic reuptake inhibition, venlafaxine has been shown to be superior in efficacy to selective serotonin reuptake inhibitors for severe major depressive disorder, treatment-resistant depression, and depressive symptom remission. Its demonstrated efficacy for both short- and long-term treatment of GAD has led to its use for obsessive-compulsive disorder and chronic pain syndromes, although inadequate clinical literature currently exists to support these latter 2 uses. In the past decade, no new or unexpected adverse events have been identified with venlafaxine therapy, except a possibly greater risk of fatal overdose compared with other serotonergic drugs, suggesting the need for caution in patients with suicidal ideation. Because venlafaxine is a potent serotonin agonist, caution must also be exercised to prevent the possibility of serotonin syndrome when used with other serotonin agonists, and its dose should be tapered very gradually to minimize the risk of a serotonin withdrawal reaction.
Venlafaxine has emerged as a successful post-SSRI-era antidepressant with an expanded range of uses since it was first marketed.
Vulvodynia is chronic vulvar burning/pain without clear medical findings. The etiology of vulvodynia is unknown and health care professionals should thoroughly rule out specific, treatable causes or factors such as dermatoses or group B Streptococcus infections. Vulvodynia is divided into 2 classes: vulvar vestibulitis syndrome is vestibule-restricted burning/pain and is elicited by touch; dysesthetic vulvodynia is burning/pain not limited to the vestibule and may occur without touch/pressure. After diagnosis, critical factors in successful patient management include education and psychological support/counseling. Unfortunately, clinical trials on potential vulvodynia therapies have been few. Standard therapy includes treating neuropathic pain (eg, tricyclic medications, gabapentin) thought to play a role. Additional therapies may be considered: pelvic floor rehabilitation combined with surface electromyography, interferon alfa, estrogen creams, and surgery. Importantly, any therapy should be accompanied by patient education and psychological support. Because definitive data on effective therapies are lacking, further clinical investigations of treatment options are warranted.
To evaluate prospectively whether generalized vulvar dysesthesia and vestibulodynia possess unique characteristics that support the theory of differing etiologies.
Women with vulvar dysesthesia for a minimum of 3 months were enrolled at the University of Michigan in 2 clinics specializing in vulvar disorders. Informed consent was obtained. Participants completed a 27-page questionnaire and had a physical examination. Differentiation of generalized vulvar dysesthesia and vestibulodynia was based on tenderness to light pressure isolated to the introitus vs. pain beyond the introitus, respectively. We compared women with the 2 diagnoses to each other on demographic characteristics, exposures, pain characteristics and physical findings using t test, Mann-Whitney U and chi 2 analysis.
Between January 26, 2001, and August 28, 2002, we enrolled 39 women, aged 18-60 years, with tenderness localized to the vestibule (vestibulodynia) and 17 with generalized vulvar dysesthesia. Women in each diagnostic group were similar in demographic and exposure characteristics. The pain characteristics were similar between the 2 groups except that recent pain was rated as worse by those with generalized vulvar dysesthesia. Activities that aggravated or relieved the pain were similar. However, women with generalized vulvar dysesthesia were more likely to state that their pain was aggravated by sitting and by washing the area. Similar results were found when using "continuous" pain rather than vulvar pain location as the outcome variable.
The characteristics of women with generalized vulvar dysesthesia are similar to those with localized pain, supporting the theory that the 2 disorders may exhibit 2 presentations on a continuum of severity seen in vulvar dysesthesia rather than 2 distinct entities.
Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Recent evidence points to the importance of the sensory component in VVS, particularly the heightened processing of tactile and pain sensation in the vulvar vestibule. The goal of the present study was to examine the neural basis of heightened sensitivity to touch (i.e. allodynia) in women with VVS. Using functional magnetic resonance imaging, we compared regions of neural activity in 14 women with VVS and 14 age- and contraceptive-matched control women in response to the application of mild and moderate pressure to the posterior portion of the vulvar vestibule. Intensity and unpleasantness ratings were recorded after each scan; these ratings were significantly higher for women with VVS than controls. All women with VVS described moderate pressure as painful and unpleasant, and 6 of the 14 women with VVS described mild pressure as painful and unpleasant. In contrast, none of the stimuli was painful for control women. Correspondingly, women with VVS showed more significant activations during pressure levels that they found to be either painful or non-painful than did controls during comparable pressure levels. During pressure described as painful by women with VVS, they had significantly higher activation levels in the insular and frontal cortical regions than did control women. These results suggest that women with VVS exhibit an augmentation of genital sensory processing, which is similar to that observed for a variety of syndromes causing hypersensitivity, including fibromyalgia, idiopathic back pain, irritable bowel syndrome, and neuropathic pain.
Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class--may among the antidepressants--favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain.
The treatment of vulvodynia is confounded by the fact that the cause is unknown in a majority of cases. Additionally, whereas we tend to separate generalized from localized vulvodynia, the characteristics of women with generalized vulvodynia are similar to those with localized pain. The 2 disorders may exhibit 2 presentations on a continuum of severity seen in generalized versus localized vulvodynia rather than 2 distinct entities.
This study aimed to examine rates and correlates of depression in a treatment-seeking sample of women with vulvodynia. A total of 53 women were independently diagnosed with vulvodynia and assessed with state-of-the-art measures of major depressive disorder (MDD) and depressive symptom severity as well as psychometrically established measures of pain severity, general functioning, sexual function and quality of life. Current and lifetime prevalence rates for MDD were 17% (n = 9) and 45% (n = 24), respectively. Women with current MDD reported significantly greater pain severity, and worse functioning and quality of life than women without current MDD. Among those with lifetime MDD, the majority (62.5%) reported that their first depressive episode occurred before the onset of vulvodynia. Rates of current MDD appeared to be lower than rates of MDD among other samples of treatment seeking chronic pain patients. In summary, co-morbid MDD is related to greater pain severity and worse functioning among women with vulvodynia.
Fibromyalgia is a chronic pain disorder for which pathophysiological mechanisms are difficult to identify and current drug therapies demonstrate limited effectiveness and significant tolerability. To date, no drugs have been officially approved for the indication of fibromyalgia, and randomized, controlled clinical trials with fibromyalgia patients are taking place to identify potential therapeutic approaches. Although emerging therapies, such as the antidepressants duloxetine and milnacipran and the antiepileptic pregabalin, offer certain efficacy, randomized controlled trials are generally difficult due to factors such as a lack of understanding of the pathophysiology and a heterogenous fibromyalgia patient population. For a significant advance in the drug treatment of fibromyalgia, novel clues are still awaited that may offer an effective therapeutic approach.
To estimate whether botulinum toxin type A is more effective than placebo at reducing pain and pelvic floor pressure in women with chronic pelvic pain and pelvic floor muscle spasm.
This study was a double-blinded, randomized, placebo-controlled trial. All participants presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm. Thirty women had 80 units of botulinum toxin type A injected into the pelvic floor muscles, and 30 women received saline. Dysmenorrhea, dyspareunia, dyschezia, and nonmenstrual pelvic pain were assessed by visual analog scale (VAS) at baseline and then monthly for 6 months. Pelvic floor pressures were measured by vaginal manometry.
There was significant change from baseline in the botulinum toxin type A group for dyspareunia (VAS score 66 versus 12; chi2 = 25.78, P < .001) and nonmenstrual pelvic pain (VAS score 51 versus 22; chi2 = 16.98, P = .009). In the placebo group only dyspareunia was significantly reduced from baseline (64 versus 27; chi2 = 2.98, P = .043). There was a significant reduction in pelvic floor pressure (centimeters of H2O) in the botulinum toxin type A group from baseline (49 versus 32; chi2 = 39.53, P < .001), with the placebo group also having lower pelvic floor muscle pressures (44 versus 39; chi2 = 19.85, P = .003).
Objective reduction of pelvic floor spasm reduces some types of pelvic pain. Botulinum toxin type A reduces pressure in the pelvic floor muscles more than placebo. Botulinum toxin type A may be a useful agent in women with pelvic floor muscle spasm and chronic pelvic pain who do not respond to conservative physical therapy. Clinical Trial Registration: Australian Clinical Trials Registry, http://www.actr.org.au/, ACTRN012605000515695
I.
The sphincteric and supportive functions of the pelvic floor are fairly well understood, and pelvic floor rehabilitation, a specialized field within the scope and practice of physical therapy, has demonstrated effectiveness in the treatment of urinary and fecal incontinence. The role of the pelvic floor in the promotion of optimal sexual function has not been clearly elucidated.
To review the role of the pelvic floor in the promotion of optimal sexual function and examine the role of pelvic floor rehabilitation in treating sexual dysfunction.
Review of peer-reviewed literature.
It has been proposed that the pelvic floor muscles are active in both male and female genital arousal and orgasm, and that pelvic floor muscle hypotonus may impact negatively on these phases of function. Hypertonus of the pelvic floor is a significant component of sexual pain disorders in women and men. Furthermore, conditions related to pelvic floor dysfunction, such as pelvic pain, pelvic organ prolapse, and lower urinary tract symptoms, are correlated with sexual dysfunction.
The involvement of the pelvic floor in sexual function and dysfunction is examined, as well as the potential role of pelvic floor rehabilitation in treatment. Further research validating physical therapy intervention is necessary.
Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is susceptible to disruption through blocking afferent signals from pelvic organs, either through anesthesia or muscle manipulation. Disruption of limbic perception with psychiatric medication similarly produces relief. Without a full disruption of both the central hypervigilance and pelvic organ dysfunction, pain recurs. To prevent recurrence, clinicians will need to include some form of therapy, either medical or cognitive, targeted at the underlying limbic hypervigilance. Further research into novel, limbic targeted therapies can hopefully be stimulated by explicitly stating the role of the limbic system in chronic pain. This hypothesis provides a framework for clinicians to rationally approach some of the most challenging patients in medicine, and can potentially improve outcomes by including management of limbic dysfunction in their treatment.
Vulvar vestibulitis syndrome is a major cause of dyspareunia. This pilot study was designed to evaluate a novel treatment approach.
This is a prospective study of 27 women with vulvar vestibulitis. The protocol included 5 treatment sessions with caudal epidural, pudendal nerve block, and vestibular infiltration of local anesthetic agents.
There were significant improvements in vestibular pain as determined by the vulvalgesiometer, McGill pain questionnaire, self-report, and the Female Sexual Functioning Inventory.
Serial multilevel nerve blocks administered for the treatment of vulvar vestibulitis is a conceptually neurophysiologically based modality that may be effective and merits a placebo-controlled study.
Vulvodynia is a fairly common dermatological symptom that often interferes with the personal, social and working activities of affected women and results in a significant loss of their quality of life. It is a persistent and tedious clinical disorder which is often resistant to conventional treatments.
The aim of this study is to evaluate the main clinical signs, associated psychopathological disorders and outcome after antidepressant treatment of patients with vulvodynia.
Eighty patients were included. Clinical characteristics and psychopathological profiles were determined by appropriate instruments. The improvement of clinical symptoms after combined antidepressant drug therapy was also evaluated. Results: Pain (70%), burning (63.7%), dyspareunia (57.5%) and stinging (56.2%) were the most commonly reported symptoms. Most patients (56.5%) showed anxiety, and 52.2% of them were reported as having a depression disorder. When evaluated by psychometric tools, 81.4% of patients scored >150 on the Life Event Scale, which means a risk >50% of suffering an illness in the near future, and patients' scores in the Dermatology Life Quality Index showed higher values than the mean of the Spanish validation group. After 6 months of combined treatment with escitalopram (10-20 mg/day), perfenazine (2-4 mg/day) and amytriptiline (10 mg/day), a complete remission of the clinical symptoms was achieved in 41% of patients. In contrast, only 12% of patients who did not follow drug treatment reported a complete resolution of the clinical symptoms.
Our results seem to confirm that vulvodynia is associated with psychiatric co-morbidity such as stress and depression. The study highlights that the psychiatric treatment may be a useful option to improve clinical symptoms. Whether these patients should be evaluated for depression or be referred to a psychiatrist, remains to be investigated.
Treatment of vulvodynia with pregabalin
- J Aranda
Aranda J. (2008) Treatment of vulvodynia with pregabalin.
Presented at the International Society for the Study of Vulvovaginal Disease XIX World Congress Meeting, Alaska.
The vulvodynia guideline
- R M Masheb
- E Wang
- C Lozano
Masheb RM, Wang E, Lozano C, et al. (2005) The vulvodynia
guideline. Journal of Lower Genital Tract Diseases 9, 40-51.