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Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy., Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 10 9 CFU per capsule) in combination with bovine lactoferrin (Respecta ® ). Each product was taken once daily for 90 days., Results: After 90 d of therapy with TIB+ Respecta ® , in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test., Conclusions: This study provides evidence that the combination of TIB+ Respecta ® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.

Background: Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It remains an underrecognized disease that responds insufficiently to therapies such as physiotherapy and medication., Aim: To assess the global efficacy of first-line therapies and factors associated with treatment escalation in women with vestibulodynia., Patients and Methods: This retrospective cohort study was conducted at the dermatology outpatient clinic of the University Hospital in Besancon (France) between 2013 and 2017 and follow-up until 2021., Results: Among 132 patients, the mean [standard deviation] age at diagnosis was 27.2 [±9.45] years, with an average duration of symptoms of 42.3 [±37.92] months. Most cases comprised provoked (75.0%) or secondary (72.7%) vestibulodynia. At least one comorbid pain or psychologic condition was identified respectively in 63 (47.7%) and 23 patients (54.5%). Vulvar hyperesthesia associated with pelvic floor muscle dysfunction was present in 121 patients (91.6%) and vulvar erethism was noted in 94 patients (71.2%). First-line treatments consisted of pelvic floor physiotherapy with biofeedback in 85% of patients, associated with amitriptyline in 36% of cases, and of additional lidocaine cream in 17%. Fifty-two patients (39%) presented at least a good response to first-line treatment, with only 21 (15%) being in complete remission, irrespective of therapeutic strategy (p = 0.25). Botulinum toxin injections were performed in 54 patients. Patients with either primary vestibulodynia (p = 0.04) or spontaneous vestibulodynia (p = 0.03) were more likely to receive this treatment., Conclusion: Our study highlights the current lack of efficacy of first-line treatments in vestibulodynia. Considering the high prevalence of muscular dysfunction, botulinum toxin injections are of particular interest despite a lack of randomized controlled trials in this indication., (Copyright © 2024. Published by Elsevier Masson SAS.)

The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar hypersensitivity induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The studies carried out to date on vulvodynia treatment with botulinum neurotoxin type A (BoNT/A) have followed generic injection protocols and reported contradictory outcomes on its effects. The aim of the present study was thus to propose a protocol for injecting BoNT/A into targeted painful points, to comprehensively assess the clinical effect of BoNT/A treatment and identify the risk/protective factors for successful treatment. Thirty-five vestibulodynia patients were treated with submucosal injections of incobotulinumtoxinA and assessed 8, 12 and 24 weeks after their treatment. Their clinical and pelvic statuses were assessed from self-reported questionnaires (Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI), Marinoff's Dyspareunia Scale (MDS), Hospital Anxiety and Depression Scale (HADS), Catastrophizing Scale (CS)), physical examinations and surface electromyography (sEMG). The patients reported a reduction in provoked vestibulodynia (FSFI, p < 0.01;

Vestibulodynia is a gynecological condition with different treatment options available, including botulinum neurotoxin type A (BoNT/A) injections into the vulvar vestibule. Unlike other treatments, no studies have assessed changes in the myoelectrical activity of the pelvic floor muscles (PFM) after BoNT/A treatment. The aim of this study was thus to evaluate these changes and to correlate them with changes in vulvar pain sensitivity. To do this, 35 patients with vestibulodynia were recruited, the myoelectrical activity of their left and right PFM was recorded with surface electromyography (sEMG), and their vulvar pain sensitivity was monitored according to Visual Analogue Scale (VAS) and an algometer, both before and after BoNT/A treatment. According to our results, patients' signals during PFM relaxation showed a significantly higher power than those of healthy women at baseline, as shown by their root mean square values (RMS), but became similar at follow-up. Patients' mean vulvar pain VAS scores significantly decreased after treatment. Furthermore, baseline-to-follow-up differences of RMS at PFM rest vs. mean VAS were significantly correlated (CC=0.48, p<0.01) so that higher reductions in the PFM activity power were associated with higher decreases in vulvar pain.Clinical Relevance- Altered PFM electrophysiological condition of patients with vestibulodynia becomes similar to healthy women's after BoNT/A treatment. This study also points to a relationship between the evolution of clinical and PFM electrophysiological conditions.

As of now, there is no adequate therapeutic strategy for provoked vestibulodynia (PVD). Pelvic Floor Muscle Therapy (PFMT) is a widely used technique in general pelvic floor rehabilitation. The objective of this study is to examine the effects of exclusive manual perineal rehabilitation with lidocaine 2% gel on PVD. During the first session, recruited patients (n = 68; mean age 31 ± 8.6; range: 18-52) received a questionnaire (Q1) on general well-being and health, pain of the genital area, sexual function, and symptoms during vaginal penetration. This questionnaire was based on a generalised questionnaire on the quality of life, the Medical Outcomes Study 36-item (SF-36), the Female Sexual Function Index (FSFI), and the Visual Analogue Scale (VAS). A second identical questionnaire with an additional set of open-ended questions concerning the assessment of the treatment was collected after treatment (Q2). A total of 45 questionnaires were completed. Statistical results showed a significant improvement of all items before and after treatment (p < 0.001): perceived general well-being and health, perceived vulvar pain, perceived sexual function, and perceived vaginal penetration. In conclusion, exclusive manual perineal rehabilitation using lidocaine 2% gel seems to be a safe and effective treatment option for vulvodynia in women., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Vulvodynia is a vulvar discomfort that occurs in the absence of any specific, clinically identifiable disorder. Few therapies have shown to be effective for the treatment of vulvodynia. In our recently published study, we tested a drug-free gel in women affected by vulvar vestibulitis. It is a cosmetic gel which acts locally without any metabolic, pharmacological or immunological effect. In order to further promote the validity of this new product, in this manuscript we analyzed the results obtained from the administration of four questionnaires in the same two groups of women affected by PVD and treated with a placebo and the new product. The questionnaires used: Female Sexual Function Index Scoring (FSFI), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale (HADS), and health-related quality of life measured by SF-36 (SF-36). The results obtained by this current analysis showed that the new gel has also proven benefits on women's quality of life and sexual function, including improvements in arousal, desire, orgasm and satisfaction.

Objective: Provoked vestibulodynia (PVD) is a challenging and distressing problem for women. The aim of this study was to examine the effect of hyaluronic acid (HA) in the management of this condition., Method: This is a retrospective review of 12 women diagnosed with PVD and treated with HA (19 mg/mL) applied, point-by-point, to the vestibular region at 2 mm intervals and at a depth of 0.5 mm. Women completed a pain VAS and a Female Sexual Function Index (FSFI) before and 45 days after treatment., Results: An improvement was observed both in mean FSFI scores (17.8 to 23.3; p = 0.003) and mean VAS scores (7.2 to 4.1; p = 0.002) after HA application respectively. However, on a telephone interview 3 months post treatment, five women (41.7 %) complained of recurrence of their dyspareunia., Conclusion: HA is a promising management option in provoked vestibulodynia. However, further larger studies with possible alternative regimens and longer follow-up are required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c., Methods: Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% oestradiol compound cream + oral placebo pill, 2) central treatment with the tricyclic antidepressant nortriptyline + placebo cream, 3) combined peripheral cream and central pill treatments, or 4) placebo cream and placebo pill. The treatment phase will last 16 weeks, with outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). First, we will compare the efficacy of treatments in alleviating pain using standardized tampon insertion with a numeric rating scale and self-reported pain on the short form McGill Pain Questionnaire. Next, we will compare the efficacy of treatments in improving perceived physical, mental, and sexual health using standardized questionnaires. Finally, we will measure cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response., Conclusion: This is the first multicenter randomized controlled trial to evaluate the efficacy of peripherally and centrally acting medications currently used in clinical practice for treating unique VBD subtypes based on distinct clinical and biological signatures., Administrative Information: Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).Key messagesPeripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs.This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles.We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches.

This paper tests the hypothesis that medications combined with behavioral sex therapy might lessen pain and restore sexuality in women with provoked vulvodynia. Three women affected by vulvodynia, otherwise healthy, in heterosexual relationship were treated at the Department of Obstetrics and Gynecology in a university hospital. In consecutive sessions of behavioral sex therapy, oral tricyclic antidepressants and vulvar applications of estrogen and hydrocortisone creams were prescribed in association with vaginal dilators and sensate focus exercises. The outcome supports the hypothesis that combined medications and sexual behavior interventions may be effective in lessening pain and restoring sexuality in women with provoked vulvodynia. The different dyadic balances observed in this small case series suggest how to best use this protocol. The positive results appear to be mostly due to behavioral sex therapy that was the new element added to the combination of pharmacological agents commonly used to treat provoked vulvodynia.

Introduction: Improved understanding of vestibulodynia pathophysiology is required to develop appropriately targeted treatments. Established features include vulvovaginal hyperinnervation, increased nociceptive signalling and hypersensitivity. Emerging evidence indicates macrophage-neuron signalling contributes to chronic pain pathophysiology. Macrophages are broadly classified as M1 or M2, demonstrating pro-nociceptive or anti-nociceptive effects respectively. This study investigates the impact of clodronate liposomes, a macrophage depleting agent, on nociceptive signalling in a mouse model of vestibulodynia., Methods: Microinjection of complete Freund's adjuvant (CFA) at the vaginal introitus induced mild chronic inflammation in C57Bl/6J mice. A subgroup was treated with the macrophage depleting agent clodronate. Control mice received saline. After 7 days, immunolabelling for PGP9.5, F4/80+CD11c+ and F4/80+CD206+ was used to compare innervation density and presence of M1 and M2 macrophages respectively in experimental groups. Nociceptive signalling evoked by vaginal distension was assessed using immunolabelling for phosphorylated MAP extracellular signal-related kinase (pERK) in spinal cord sections. Hyperalgesia was assessed by visceromotor response to graded vaginal distension., Results: CFA led to increased vaginal innervation (p < 0.05), increased pERK-immunoreactive spinal cord dorsal horn neurons evoked by vaginal-distension (p < 0.01) and enhanced visceromotor responses compared control mice (p < 0.01). Clodronate did not reduce vaginal hyperinnervation but significantly reduced the abundance of M1 and M2 vaginal macrophages and restored vaginal nociceptive signalling and vaginal sensitivity to that of healthy control animals., Conclusions: We have developed a robust mouse model of vestibulodynia that demonstrates vaginal hyperinnervation, enhanced nociceptive signalling, hyperalgesia and allodynia. Macrophages contribute to hypersensitivity in this model. Macrophage-sensory neuron signalling pathways may present useful pathophysiological targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castro, Harrington, Chegini, Matusica, Spencer, Brierley, Haberberger and Barry.)

Background: Vulvodynia is a condition characterised by pain in the vulva lasting more than three months and for which no obvious aetiology can be found. It affects around 8% of women and has significant negative impacts on quality of life. There is a paucity of research on healthcare management pathways and the use of evidence-based treatments in an Australian community setting., Aims: To explore which healthcare professionals Australian women with vulvodynia seek treatment from, and which treatments are recommended, provided, or prescribed by these healthcare professionals., Materials and Methods: A cross-sectional online survey was conducted from May 2019 to August 2019. Women were eligible to participate if they had been diagnosed with vulvodynia by a healthcare professional, were currently living in Australia, and were over 18 years old., Results: Fifty respondents meet the inclusion criteria, with a mean age of 30.5 years. On average, respondents reported seeing four different types of healthcare professionals in the management of their vulvodynia, with general practitioners (GPs) (98%), medical specialists (96%), and physiotherapists (80%) being the three most commonly consulted. Most respondents reported seeing multiple GPs (>87%), multiple medical specialists (>77%), and multiple physiotherapists (50%). The most commonly prescribed interventions were pelvic floor down-training exercises (76%), topical (70%) and oral (70%) medication, and vulvodynia information (56%)., Conclusions: Australian women with vulvodynia seek help from several professionals and receive a variety of treatments for their pain. Of concern is many treatments that are being offered clinically have very little peer-reviewed evidence of effectiveness in vulvodynia., (© 2021 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia in premenopausal women, characterized by pain with light touch to the vulvar vestibule surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction, infertility, depression, and even suicide. Yet, its etiology is unclear. No effective medical therapy exists; surgical removal of the painful vestibule is the last resort. In LPV, the vestibule expresses a unique inflammatory profile with elevated levels of pro-nociceptive proinflammatory mediators prostaglandin E 2 (PGE 2 ) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds. Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the body, hold promise as an LPV treatment by resolving inflammation without impairing host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE 2 production by vulvar fibroblasts, administered either before or after inflammatory stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification with mechanical sensitivity threshold determination, topical treatment with the SPM, maresin 1, decreased sensitivity and suppressed PGE 2 levels. Docosahexaenoic acid, a precursor of maresin 1, was also effective in reducing PGE 2 in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall, SPMs and their precursors may be a safe and efficacious for LPV. Perspective: Vulvodynia, like many pain conditions, is difficult to treat because disease origins are incompletely understood. Here, we applied our knowledge of more recently discovered vulvodynia disease mechanisms to screen novel therapeutics. We identified several specialized pro-resolving mediators as likely potent and safe for treating LPV with potential for broader application., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale: Vulvodynia is a common chronic gynecological disease that affects approximately 16% of women, although it is rarely diagnosed. However, no known effective treatment exists. The etiology of vulvodynia is unknown and may be heterogeneous and multifactorial, so it is difficult-if not impossible-to improve this condition using 1 treatment method. Reports have shown that vulvodynia has an element of neuropathic pain. Although the role of the sympathetic nervous system in neuropathic pain is controversial, sympathetic nerve blocks have long been used to treat patients with chronic pain giving good results. A ganglion impar block (GIB), a sympathetic nerve block technique, may effectively manage pain and discomfort in patients with vulvodynia., Patient Concerns: Four patients suffering from chronic vulvar pain for 6 months-10 years were referred by gynecologists. The gynecologists could not identify the cause of the chronic vulvar pain, and symptoms were not improving by conservative therapy with medication. Patients complained of various chronic vulvar pain or discomfort. The initial visual analog scale (VAS) scores were 8 or 9 out of 10, and Leeds assessment of neuropathic symptoms and signs pain scale score was more than 12 out of 24. The review of gynecological medical records confirmed whether they showed allodynia during the cotton swab test and hyperalgesia to pin-prick test., Diagnoses: All patients were diagnosed with vulvodynia., Interventions: All patients were treated with a GIB, once in 2 patients, 3 times in 1 patient, and 4 times (1 alcoholic neurolysis) in the other patient, under fluoroscopic guidance., Outcomes: After the procedures, the VAS score and the leeds assessment of neuropathic symptoms and signs (LANSS) pain scale score were decreased to less than 2 and 5, respectively, in all patients. Follow-up observations for 6 months-2 years revealed that 2 patients' symptoms entirely or nearly entirely improved and did not require further treatment. The pain of the remaining patients were well controlled with medications only., Lessons: GIB is a good treatment option for patients suffering from chronic pain and discomfort caused by vulvodynia., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The purpose of this study was to compare techniques and pain scales that assess tenderness in the vulvar vestibule in provoked vestibulodynia, using the cotton swab test and a vulvalgesiometer, and assess topical lidocaine solution with each., Materials and Methods: This randomized study at a specialty vulvar clinic evaluated tender vestibules of reproductive-aged women with vestibulodynia using light rolling cotton swab touch at 6 sites and evaluated the vulvalgesiometer at 2 sites, randomizing the order of the initial tool. Participants reported pain using the Numerical Rating Scale 0-10 and the Verbal Pain Scale 0-3. With the vulvalgesiometer, the pain tolerance threshold was measured using forces of 10, 25, 50, 100, 200, and 300 g. After both initial tests, lidocaine 4% topical solution was applied for 3 minutes, and the swab test and vulvalgesiometer were repeated in the order initially performed, constituting the lidocaine test. Data analysis used t tests, Fisher exact tests, Wilcoxon signed rank tests, and Spearman rank correlation., Results: Sixteen patients completed the study, 8 starting with each instrument. Light swab touch evoked significant pain, and lidocaine reduced pain to zero or mild levels. The pain threshold was 25 g, and only 38% could tolerate testing past 100 g without lidocaine. The Verbal Pain Scale correlated well with the Numerical Rating Scale., Conclusions: Light rolling cotton swab touch using the 4-item verbal scale can map vestibulodynia tenderness that can be extinguished by lidocaine, consistent with distinguishing a mucosal condition. Forces by vulvalgesiometer of greater than 100-200 g may evoke pain other than mucosal allodynia., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021, ASCCP.)

Background: Vulvodynia and pudendal neuralgia comprise significant contributors to vulvar-related pain and its impact on daily life., Aim: A retrospective clinical audit was conducted at the Women's Health & Research Institute of Australia, Sydney, to determine the pattern of use and the efficacy of the application of topical amitriptyline 0.5% plus oestriol 0.03% in organogel (AOO), to the vulvar vestibule in reducing the impact of pain on daily life., Materials and Methods: There were 1174 patients who received a script from May 2017 until February 2020: 1054 patients agreed to be contacted and had a valid email address., Results: There were 376 (35.7%) patients who replied. Pain with intercourse was the main indication for use. Treatment was rated effective by 51.2% (95% CI: 35.4-66.8%) of patients less than 30 years of age, 66.7% (95% CI: 57.3-74.9%) of patients 30-50 years of age, and 58.3% (95% CI: 50.9-65.4%) in patients over 50. Stinging at the site of application was the most commonly reported side effect., Conclusion: Topical AOO is an effective and well-tolerated treatment for vulvar pain., (© 2021 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Vulvar lichen sclerosus is a progressive dermatitis with significant itching, pain, and sexual dysfunction., Objective: To investigate topical steroid use and clinical improvement across multiple specialties., Methods: Retrospective cohort study at dermatology, gynecology, and vulvovaginal specialty clinics from 2012 to 2017. Descriptive statistics and panel logistic regression were performed., Results: A total of 333 women attended 1525 visits (median 6/patient; range, 1-24 visits). Patients used steroids exactly as prescribed at 66% of visits, less than prescribed at 26%, and not at all at 8%. Versus no use, exact use improved symptoms (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.2-9.6) and physical examination findings (OR, 6.9; 95% CI, 2.7-17.6) more than infrequent steroid use (symptoms: OR, 2.5; 95% CI, 1.2-5.4; physical examination findings: OR, 4.2; 95% CI, 1.6-11.0). Sexual activity status was noted in 93% of vulvovaginal, 29% of gynecology, and 0% of dermatology visits. At intake, 42% of women were sexually inactive because of pain; of these, 37% became sexually active after steroid treatment. Steroid adherence was not associated with change in sexual activity., Conclusions: Women with vulvar lichen sclerosus improve more when topical steroids are used exactly as prescribed, although some improvement occurs with imperfect use. Sexual activity documentation is inconsistent, limiting quality of life follow-up., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate pain reduction after two injections of 50 units botulinum toxin A compared with placebo for provoked vestibulodynia., Methods: We conducted a double-blinded, placebo-controlled randomized trial of 50 units botulinum toxin A or placebo injected in the bulbocavernosus muscles twice, 3 months apart, in women with provoked vestibulodynia. Primary outcome was self-reported dyspareunia or pain at tampon use on a visual analog scale (VAS, 0-100). Secondary outcomes were pain at weekly tampon insertion (VAS score), reduction of pelvic floor hypertonicity (measured with a vaginal manometer), adverse events, and sexual function and distress. A sample size of 38 participants for each group was calculated to achieve a statistical power of 80% based on an effect size of 20 VAS units (0-100) (mean score range 56-76±31 SD)., Results: Between May 2016 and June 2018, 124 women with provoked vestibulodynia were assessed, and 88 were randomized to botulinum toxin A (BTA group, n=44) or placebo (placebo group, n=44). Primary outcome showed a lower but statistically nonsignificant pain rating by 7 VAS units (95% CI -15.0 to 0.4) in the BTA group compared with the placebo group. Secondary results showed a significant decrease in pain at weekly tampon insertion by 11 VAS units (95% CI -16.6 to 6.0) with botulinum toxin A injection. The vaginal manometer measured lower maximum contraction strength by 7 mm Hg (95% CI -12.7 to -2.4) and lower 10-second endurance strength by 4 mm Hg (95% CI -7.72 to -1.16) in the BTA group compared with the placebo group. No changes were observed for sexual function and distress, but there was a significant increase in women attempting vaginal intercourse in the BTA group (0.27, 95% CI 0.06-0.48). No severe adverse events were reported., Conclusion: Twice-repeated injections of 50 units of botulinum toxin A in women with provoked vestibulodynia did not reduce dyspareunia or pain at tampon use, but secondary outcomes suggested positive effects of the treatment., Clinical Trial Registration: ClinicalTrials.gov, NCT02773641.

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8 + CD103 + T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ 9 -tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.

Background: Previous studies using botulinum toxin type A (BT) to treat provoked vestibulodynia (PVD) reported conflicting findings, possibly attributable to singular injections or low doses. We assessed PVD treatment effectiveness with high-dose single injections of BT (50 or 100 units) versus placebo, and then repeat BT 100 U injections over 6 months., Methods: This was a randomized, double-blind, three-arm, placebo-controlled study with 33 PVD patients. BT 50 U (arm A), 100 U (arm B) or saline (arm C) were injected subcutaneously into the dorsal vulvar vestibulum and pain was assessed after 3 months. The investigation proceeded as an unblinded exploratory analysis, in which symptomatic patients received a BT 100 U injection. Symptomatic patients in arm C received a second BT 100 U injection at the 6-month visit. Symptoms were measured at 3-month cycles using: (1) cotton swab-provoked visual analogue scale (VAS), (2) von Frey filaments, and (3) Marinoff dyspareunia scale., Results: The three groups were comparable in terms of demographics and baseline clinical characteristics. Three months after the initial injection, no significant differences in pain were observed among the study arms, yet significant improvements occurred within all groups using the von Frey filaments test. Results from the exploratory analyses showed repeat injections of 100 U BT over 6 months led to significant pain reduction (VAS and von Frey filaments). Fifty-eight percent (7/12) of patients assessable after repeat injections were symptom-free or had ≥ 2 VAS reduction. Adverse events were minor and no serious adverse events occurred during the RCT or exploratory analysis., Conclusions: PVD symptoms after one subcutaneous injection of BT (50 or 100 units) did not significantly differ compared to placebo, yet all three study arms experienced a reduction in pain 3 months after a single injection. Exploratory analyses indicated that repeat high-dose BT injections may significantly reduce pain over 6 months., Trial Registration: This trial was registered with the Swiss Medical Agency (reference number: 2007DR2102) in 2007.

Introduction: We wanted to evaluate the efficacy of botulinum toxin type A (botulinum toxin) treatment on vulvodynia refractory to conventional treatment., Material and Methods: A follow-up study on botulinum toxin treatment was conducted at Aarhus University Hospital (n = 109). Seventy-nine completed the follow-up. The women included had localized provoked vulvodynia, refractory to first line treatment and were treated with 100*I.E. botulinum toxin electromyography (EMG) guided in the musculus levator ani in the period from March 2012 to May 2015(1). The outcome measures were: Dyspareunia, Negative Interference in Quality of Life (NIQL) and cotton swab test all rated on the numerical rating scale (NRS) and active vitae sexualis. Follow-up was conducted at six months., Results: The women experienced significant improvements on, dyspareunia, which decreased to 5.82 from 7.82 (p < 0.01), NIQL to 6.19 from 7.88 (p < 0.01) and the cotton swab test to 5.50 from 6.81 (p < 0.01). No significant effect on Active Vitae Sexualis was found (p = 0.25)., Conclusion: Women injected with 100*I.E. botulinum toxin EMG guided, diagnosed with localized provoked vulvodynia refractory to conventional non invasive treatment, had a reduction in dyspareunia and improved quality of life. Injection of botulinum toxin had no significant effect on vitae sexualis. Randomized controlled trials are, however, much needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Sexual dysfunction is common in women with vulvodynia., Objective: The purpose of this study was (1) to evaluate whether extended-release gabapentin is more effective than placebo in improving sexual function in women with provoked vulvodynia and whether there is a relationship between treatment outcome and pelvic pain muscle severity that is evaluated by palpation with standardized applied pressure and (2) to evaluate whether sexual function in women with provoked vulvodynia would approach that of control subjects who report no vulvar pain either before or after treatment., Study Design: As a secondary outcome in a multicenter double-blind, randomized crossover trial, sexual function that was measured by the Female Sexual Function Index was evaluated with gabapentin (1200-3000 mg/d) compared with placebo. Pain-free control subjects, matched by age and race, also completed Female Sexual Function Index for comparison., Results: From August 2012 to January 2016, 230 women were screened at 3 academic institutions, and 89 women were assigned randomly to treatment. Gabapentin was more effective than placebo in improving overall sexual function (adjusted mean difference, 1.3; 95% confidence interval, 0.4-2.2; P=.008), which included desire (mean difference, 0.2; 95% confidence interval, 0.0-3.3; P=.04), arousal (mean difference, 0.3; 95% confidence interval, 0.1-0.5; P=.004), and satisfaction (mean difference, 0.3; 95% confidence interval, 0.04-0.5; P=.02); however, sexual function remained significantly lower than in 56 matched vulvodynia pain-free control subjects. There was a moderate treatment effect among participants with baseline pelvic muscle pain severity scores above the median on the full Female Sexual Function Index scale (mean difference, 1.6; 95% confidence interval, 0.3-2.8; P=.02) and arousal (mean difference, 0.3; 95% confidence interval, 0.1-0.6; P=.01) and pain domains (mean difference, 0.4; 95% confidence interval, 0.02-0.9; P=.04)., Conclusion: Gabapentin improved sexual function in this group of women with provoked vulvodynia, although overall sexual function remained lower than women without the disorder. The most statistically significant increase was in the arousal domain of the Female Sexual Function Index that suggested a central mechanism of response. Women with median algometer pain scores >5 improved sexual function overall, but the improvement was more frequent than the pain domain. We hypothesize that gabapentin may be effective as a pharmacologic treatment for those women with provoked vulvodynia and increased pelvic muscle pain on examination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Vulvodynia is the most common type of chronic pelvic pain and dyspareunia in premenopausal women. The effect of drugs for the treatment of vulvodynia remains poorly discussed., Objectives: To conduct a systematic review of randomised controlled studies which assess medications used to treat vulvar pain in vulvodynia., Search Strategy: Web of Science, Cochrane Library, EBSCO Academic, LILACS and MEDLINE were searched from 1985 to September 2016., Selection Criteria: Randomised controlled trials comparing any kind of medication for vulvodynia treatment with placebo or with another medication in adult patients were included., Data Collection and Analysis: The two investigators independently conducted data extraction. The synthesis was provided by the pain reduction index. Study quality assessment was performed using the Cochrane Handbook for Systematic Reviews of Intervention and analysis of publication bias was conducted., Main Results: Five studies were included in qualitative synthesis. Number of participants varied from 30 to 133 participants among the eligible studies, resulting in a total of 297 patients. The pain reduction rates of patients with vulvodynia assessed by Q-tipped cotton test and visual analogue scale varied between studies. Placebo was shown to be as effective as any medication., Conclusions: There is a need for further studies evaluating topical monotherapy for the treatment of vulvodynia, as they are the main drugs used in clinical practice., Tweetable Abstract: No medication has shown impact on vulvar pain in vulvodynia. There is evidence of a placebo effect., (© 2018 Royal College of Obstetricians and Gynaecologists.)

The study aimed to assess the effects of ospemifene on vulvar vestibule in postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of the vulvar vestibule was also conducted. Patients also underwent current perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five patients (94.6%) completed the treatment. Hot flashes were the most frequent adverse effects, but this led to a discontinuation of therapy in three patients (5.4%). After therapy, there was a statistically significant decrease from the baseline in the mean scores for dryness, burning, and dyspareunia and reduction of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p ≤ 002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a difference in CPT values for all nerve fibers and more consistent for C fibers (-38% of sensitivity). These results confirm the efficacy of ospemifene on postmenopausal vestibular symptoms and signs; moreover, the drug was effective in normalizing vestibular innervation sensitivity.

Objective: To evaluate whether extended-release gabapentin is more effective than placebo among women with vulvodynia., Methods: In a multicenter double-blind, placebo-controlled randomized crossover trial, gabapentin (1,200-3,000 mg/d) was compared with a placebo. The primary outcome was mean pain intensity (0, no pain at all to 10, worst pain ever) on the tampon test (a standardized tampon insertion and removal test used as a surrogate marker for dyspareunia) during the last 7 days of the maintenance phase. Secondary outcomes included sexual intercourse pain and daily pain. A sample size of 53 provided 90% power to detect a 1-point reduction on the tampon test (.05 level, two-sided) between the two treatment phases., Results: From August 2012 to January 2016, 230 women were screened at three academic institutions and 89 (mean age 37 years; 65% black) were randomized: 45 to gabapentin first and then placebo and 44 to placebo first and then gabapentin. Tampon test pain with gabapentin was not different compared with the placebo (adjusted mean 4.0, 95% CI 3.0-4.9 vs 4.3, 95% CI 3.4-5.2, difference -0.3, 95% CI -0.7 to 0.0; P=.07). Gabapentin also did not improve pain over placebo for sexual intercourse pain (adjusted mean 3.9, 95% CI 2.4-5.3 vs 4.0, 95% CI 2.5-5.4, difference -0.1, 95% CI -0.9 to 0.6; P=.76) and daily pain (adjusted mean 2.7, 95% CI 1.8-3.6 vs 2.9, 95% CI 2.0-3.8, difference -0.2, 95% CI -0.5 to -0.2; P=.36). Subset analyses found that longer pain duration and oral contraceptive nonuse were associated with minimal improvement in tampon test pain with gabapentin., Conclusion: In this cohort, extended-release gabapentin, as compared with a placebo, did not reduce tampon test pain. These data do not support the recommendation of gabapentin alone as treatment for vulvodynia., Clinical Trial Registration: ClinicalTrials.gov, NCT01301001.

Background: Vulvodynia is a poorly characterized condition with multiple treatment options that have been described as largely ineffective in research settings., Aim: To describe treatment patterns in women enrolled in the National Vulvodynia Registry and determine if there is an association between selected treatments and patient-reported outcomes such as pain, sexual function, and psychological distress after 6 months of treatment., Methods: Participants completed questionnaires on general medical history and patient-reported outcomes using the short-form McGill Pain Questionnaire, the Female Sexual Function Index, the Short Form-12 quality-of-life questionnaire, the Coping Strategies Questionnaire, and the State-Trait Anxiety Inventory. The evaluation also included pain sensitivity assessment of the vaginal mucosa using a cotton-tipped applicator and the vaginal muscles using a single-digit. In this prospective cohort study, all measurements were collected at baseline and again at 6 months after treatment., Outcomes: Type of treatment, number of treatments, self-reported pain intensity, dyspareunia, and pain-related psychological distress measures are reported at baseline and 6 months., Results: Of 344 women enrolled, 282 received treatment; 78 different treatments were identified and categorized by type (eg, topical, oral, physical therapy) and number. The most commonly used treatments were topical (85%, n = 241), physical therapy (52%, n = 147), and oral medications (45%, n = 128). Notably, 73% of participants received ≥2 treatments. There was no association between type or number of treatments and patient characteristics. At 6 months, women reported improvements in general pain (P = .001), pain during intercourse (P = .001), catastrophizing (P = .000), and anxiety (P = .000). The Short Form-12 quality-of-life questionnaire showed improvements in physical limitations (P = .024), emotional limitations (P = .003), well-being (P = .025), and social function (P = .010). However, all domains of the Female Sexual Function Index indicated worsening in sexual function (P = .000) except for pain., Clinical Translation: Multi-modal treatments were most commonly used in clinical practice and improvements in patient-reported outcomes such as quality of life, distress, and pain were noted; however, participants who returned at 6 months continued to report poor sexual function., Conclusions: Strengths include a prospective and long-term study design that evaluated women in clinical settings. Limitations include a high rate of loss to follow-up for certain measures and inability to evaluate efficacy of individual treatments. In a setting where women were receiving highly specialized care, we found wide variation in the type and number of treatments used to treat vulvodynia. Despite this heterogeneity in treatment selection, women reported significant improvements in all study measures except sexual function. Lamvu G, Alappattu M, Witzeman K, et al. Patterns in Vulvodynia Treatments and 6-Month Outcomes for Women Enrolled in the National Vulvodynia Registry-An Exploratory Prospective Study. J Sex Med 2018;15:705-715., (Published by Elsevier Inc.)

Objective: To describe patient characteristics of women diagnosed with generalized unprovoked vulvodynia (GUV) and to estimate efficacy and tolerability of treatment., Material and Methods: Retrospective observational study in 241 women who presented with GUV at three vulvar disease clinics in Rotterdam, The Netherlands during 1996-2013. Main outcome was efficacy of amitriptyline, gabapentin or pregabalin treatment., Results: The median duration of symptoms was 24 months and median age 62 years (range 36-89). Most of the patients reported a burning sensation, often worsened by sitting, urinating or having intercourse. Treatment with either amitriptyline, gabapentin or pregabalin produced long lasting pain relief in 60% and temporary pain relief in 10%, while treatment was not successful in 30% of the patients. Around 30% of the patients had to stop their medication due to side effects. In 44 of the 241 (18%) women signs of vulvar dermatoses were present that could not explain the symptoms. These women experienced the same therapeutic efficacy as those without any visible abnormalities (chi-square goodness of fit p=0.49)., Conclusions: Amitriptyline, gabapentin and pregabalin produced long lasting pain relief in most of the women with GUV. The 2015 International Society for the Study of Vulvovaginal Disease nomenclature acknowledges the concomitant presence of vulvar dermatoses and vulvodynia. This enables treatment of both conditions simultaneously, a situation that occurs regularly according to our study. We advocate that women with symptoms of GUV, with or without the presence of vulvar dermatoses, receive a therapeutic trial with drugs such as amitriptyline., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To assess the efficacy of conjugated equine estrogen cream in reducing dyspareunia associated with secondary provoked vestibulodynia., Methods: We conducted a randomized, double-blind, placebo-controlled trial that included women with secondary provoked vestibulodynia. Participants were randomly allocated to daily application of conjugated equine estrogen cream on the vulvar vestibule (estrogen group) or daily application of a similar placebo cream (placebo group). All patients were evaluated before and after eight weeks of treatment, using a visual analogue scale for superficial dyspareunia (primary outcome), the McGill Pain Questionnaire for superficial dyspareunia, the Female Sexual Function Index for sexual satisfaction, and vulvoscopy for vestibular erythema., Results: The targeted recruitment for this study was 44 women, but because of funding shortfalls recruitment was limited to 20 women. These 20 participants were randomly assigned to two groups of 10. Improvement of superficial dyspareunia on the visual analogue scale was not significantly different between the two groups (estrogen group: 27% improvement vs. placebo group: 3% improvement, P = 0.29). However, the use of conjugated equine estrogen cream was associated with a significant post-treatment improvement in superficial dyspareunia and in all three secondary outcomes (P < 0.05), whereas this was not the case with the use of placebo., Conclusion: Daily application of conjugated equine estrogen cream to the vulvar vestibule could potentially reduce superficial dyspareunia in women with secondary provoked vestibulodynia, but a randomized trial with adequate statistical power will be required to demonstrate this., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS)., Methods: Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16.67 mg. Symptoms of burning and pain were assessed using a 10-cm visual analog scale and the short form of the McGill-Melzack Pain Questionnaire., Results: Among 84 women who were randomized, the mean ± standard deviation dose of amitriptyline was 21.7 ± 6.6 mg/day, without statistical difference between the two groups. Pain, as assessed using both the pain rating index of the visual analog scale and the short-form McGill Pain Questionnaire, decreased significantly in both trial groups, with a greater effect seen with the addition of ALA and n-3 PUFAs. The addition of ALA/n-3 PUFAs to amitriptyline treatment was also associated with improvements in dyspareunia and pelvic floor muscle tone. The overall incidence of adverse events was low, and none led to treatment discontinuation., Conclusions: The addition of ALA/n-3 PUFAs to amitriptyline treatment in patients with VBD/PBS appears to improve outcomes and may allow for a lower dosage of amitriptyline, which may lead to fewer adverse effects., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the current practice patterns for the management of vulvodynia in the United States (US) and to estimate healthcare costs related to this condition., Methods: Truven MarketScan Commercial Claims and Encounters databases for years 2009-2013 were utilized for analysis. The study cohort included women, 18 years or older, with a diagnosis of vulvodynia (ICD-9 625.70), who had been continuously enrolled for 360 days from the date of diagnosis. Measures included the most common prescriptions, primary procedures, associated diagnoses, as well as net healthcare costs. Statistical Analysis Software 9.3 was used for statistical analysis., Results: Among 24,122 subjects with vulvodynia, 12,584 met enrollment criteria. Mean age was 41.0 ± 12.9 years. Vulvar biopsy (29.6%), urinalysis (27.8%), urine culture (27.5%) and wet mount for infectious agents (25.5%) were commonly performed primary procedures. The most common prescriptions were antidepressants (32.4%), followed by opiates (27.6%), antifungals (26.1%), and steroidal agents (22.7%). Vulvodynia was frequently associated with vulvovaginitis (32.0%), urinary tract infection (20.6%), and chronic fatigue (18.6%). The mean net cost per patient including pharmacy claims during the follow-up period was $9591.80 (SD $14,595.52; 95% CI $9333.45-$9850.13)., Conclusions: Our findings confirm great variation in the current management of vulvodynia. The variety of treatment approaches is a reflection of the poor current understanding of the etiology and pathophysiology of vulvodynia. Further research is needed to determine which treatments are most effective in the management of each subtype of vulvodynia.

Background: Successful recruitment in clinical trials for chronic pain conditions is challenging, especially in women with provoked vulvodynia due to reluctance in discussing pain associated with sexual intercourse. The most successful recruitment methods and the characteristics of women reached with these methods are unknown., Objective: To compare the effectiveness and efficiency of four recruitment methods and to determine socioeconomic predictors for successful enrollment in a National Institutes of Health-sponsored multicenter clinical trial evaluating a gabapentin intervention in women with provoked vulvodynia., Methods: Recruitment methods utilized mass mailing, media, clinician referrals and community outreach. Effectiveness (number of participants enrolled) and efficiency (proportion screened who enrolled) were determined. Socioeconomic variables including race, educational level, annual household income, relationship status, age, menopausal status and employment status were also evaluated regarding which recruitment strategies were best at targeting specific cohorts., Results: Of 868 potential study participants, 219 were enrolled. The most effective recruitment method in enrolling participants was mass mailing ( p < 0.001). There were no statistically significant differences in efficiency between recruitment methods ( p = 0.11). Relative to clinician referral, black women were 13 times as likely to be enrolled through mass mailing (adjusted odds ratio 12.5, 95% confidence interval, 3.6-43.1) as white women. There were no differences in enrollment according to educational level, annual income, relationship status, age, menopausal status, or employment status and recruitment method., Conclusion: In this clinical trial, mass mailing was the most effective recruitment method. Race of participants enrolled in a provoked vulvodynia trial was related to the recruitment method.

Localised provoked vulvodynia (LPV) is a common, chronic, and disabling condition: patients experience profound pain and a diminished quality of life. The aetiologic origins of vulvodynia are poorly understood, yet recent evidence suggests a link to site-specific inflammatory responses. Fibroblasts isolated from the vestibule of LPV patients are sensitive to proinflammatory stimuli and copiously produce pain-associated proinflammatory mediators (IL-6 and PGE 2 ). Although LPV is a multifactorial disorder, understanding vulvar inflammation and targeting the inflammatory response should lead to treatment advances, especially for patients exhibiting signs of inflammation. NFκB (already targeted clinically) or other inflammatory components may be suitable therapeutic targets., Tweetable Abstract: Vulvodynia is a poorly understood, prevalent, and serious women's health issue requiring better understanding to improve therapy., Competing Interests: of Interests: No conflicts of interest to disclose. The ICMJE disclosure forms are available as online supporting information., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Background: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities., Objective: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABA A receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain., Methods: 6-MeOF was evaluated for analgesic effect in the hot plate test and streptozotocin-induced diabetic neuropathic pain in female rats using von Frey hairs. The possible involvement of opioidergic and GABAergic mechanisms was investigated using naloxone and pentylenetetrazole (PTZ) antagonists, respectively. The biodistribution of 6-MeOF in plasma and CNS was examined using a validated HPLC/UV analytical method. The binding affinity of 6-MeOF with opioid and GABA receptors was studied using molecular docking simulation approach., Results: 6-MeOF (10 and 30mg/kg) attenuated the acute phasic thermal nociception in the hot plate test while in the case of streptozotocin-induced diabetic neuropathy model, 6-MeOF (10 and 30mg/kg) produced static/dynamic anti-allodynic (increased paw withdrawal threshold and latency) as well as static/dynamic anti-vulvodynic effects (increased flinching response threshold and latency), when compared to the vehicle and standard gabapentin (75mg/kg). In silico studies depicted the preference of 6-MeOF for the delta- and kappa-opioid and GABA A receptors. Moreover, the pharmacokinetic profile revealed a quick appearance of 6-MeOF in the systemic circulation and brain areas with maximum concentration observed after 30min in the amygdala, brain stem and cerebral cortex., Conclusion: 6-MeOF readily crosses the blood brain barrier and may be effective in attenuating the diabetes-induced allodynia as well as vulvodynia, probably through interactions with the GABAergic and opioidergic systems., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Vulvodynia is a common and debilitating disease, for which treatments are often of limits efficacy. As the Impar node receives nociceptive afferents from pelvis and perineum, it is a potential therapeutic target to treat pain in this region. The objective of the study was to evaluate the relevance of ropivacaine Impar node infiltration in patients suffering from rebel vulvodyny., Methods: This was a retrospective, single-center study. The Impar node infiltrations were performed by a single operator in eight patients suffering from rebel vulvodynia. Ropivacaine and iopamidol were administered in prone position with a lateral approach under scanner. The anaesthetic diagnostic block of the Impar node was positive in all eight patients included in the study. Thereafter these patients benefited of 2 additional therapeutic infiltrations. Subsequently, an infiltration of the node with 100UI of botulinum toxin was performed in two patients with a bilateral approach under scanner. The analgesic efficacy was evaluated by a Visual Analogic Scale (VAS) before, immediately after, and at day 15 following the infiltration. A subjective evaluation of pain comprising the percentage of overall improvement and duration of analgesic efficacy was performed after the third infiltration., Results: Comparison of the VAS before and immediately after the Impar block showed in the first anesthetic block a significant decrease in pain median VAS from 51/100 to 16/100 (P=0.01). Similarly, for the second block, VAS decreased from 52.5/100 to 15/100 (P=0.02). The maximal pain reported on Day 15, was significantly lower after the third infiltration than that after the first (P=0.03). Five patients reported an overall improvement in their quality of life of over 50%, which lasted an average of six weeks. A long lasting effectiveness was obtained in the two patients who benefited of the botulinum toxin., Conclusion: The infiltration of Impar node is an interesting technique for patients suffering of rebel vulvodynia., Level of Evidence: 4., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: This 13-week randomized clinical trial aimed to compare group cognitive-behavioral therapy (GCBT) and a topical steroid in the treatment of provoked vestibulodynia, the most common form of dyspareunia., Method: Participants were 97 women randomly assigned to 1 of 2 treatment conditions and assessed at pretreatment, posttreatment and 6-month follow-up via structured interviews and standard questionnaires pertaining to pain (McGill Pain Questionnaire, 11-point numerical rating scale of pain during intercourse), sexual function (Female Sexual Function Index, intercourse frequency), psychological adjustment (Pain Catastrophizing Scale, Painful Intercourse Self-Efficacy Scale), treatment satisfaction, and participant global ratings of improvements in pain and sexuality., Results: Intent-to-treat multilevel and covariance analyses showed that both groups reported statistically significant reductions in pain from baseline to posttreatment and 6-month follow-up, although the GCBT group showed significantly more pain reduction at 6-month follow-up on the McGill Pain Questionnaire. The 2 groups significantly improved on measures of psychological adjustment, and the GCBT group had significantly greater reductions in pain catastrophizing at posttreatment. Both groups' sexual function significantly improved from baseline to posttreatment and 6-month follow-up, and the GCBT group was doing significantly better at the 6-month follow-up. Treatment satisfaction was significantly higher in the GCBT group, as were self-reported improvements in pain and sexuality., Conclusions: Findings suggest that GCBT may yield a positive impact on more dimensions of dyspareunia than a topical steroid, and support its recommendation as a first-line treatment for provoked vestibulodynia., ((c) 2016 APA, all rights reserved).)

Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms., Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia., Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency., Conclusions: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed.

Background: Provoked vestibulodynia is a relatively common condition that affects sexual activity. Multidisciplinary care is indicated and OnabotulinumtoxinA injections are safe and effective treatment in this indication., Aims: To assess the long-term efficacy of OnabotulinumtoxinA in provoked vestibulodynia., Materials and Methods: Twenty-one patients treated with OnabotulinumtoxinA injections (50U in each bulbospongiosus muscle) 24 months prior to the study were included. Data on pain [assessed using a visual analogue scale (VAS)], quality of life [measured by the Dermatology Life Quality Index (DLQI)] and quality of sex life [assessed using the Female Sexual Function Index (FSFI)] were collected before treatment, and 3 and 24 months after injection., Results: Nineteen patients participated in the study and 37% had no pain after 24 months. Significant improvements were noted in the VAS, DLQI and FSFI scores between baseline and 24 months post treatment (P < 0.0001). After 24 months, 18 patients (95%) were able to have sexual intercourse. This study was open and non-controlled., Discussion and Conclusion: 100U OnabotulinumtoxinA injections constitute an effective treatment in provoked vestibulodynia with results maintained after 2 years. They significantly improve pain, and have a positive impact on patient quality of life and sex life. Beneficial effects continue in the long-term, allowing patients to resume sexual activity., (© 2015 European Academy of Dermatology and Venereology.)

Vulval and vaginal symptoms are common after the menopause and are frequently assumed to be due to the normal physiological changes that occur at this time. However, there are several important dermatoses that can occur in this patient group which need accurate diagnosis and appropriate management. This review discusses the clinical features and basic management of some of the common vulval problems occurring after the menopause., (© The Author(s) 2015.)

Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5-29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin.

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.

Background: The prevalence of idiopathic vulvodynia and proctodynia is high. Pain management with anti-depressants and anti-epileptics may induce undesirable side effects. Therefore, topical baclofen cream and palmitoylethanolamide might be new therapeutic options., Case: A 33-year-old woman with intractable chronic vulvar and anal pain had to abstain from sexual intercourse and could neither cycle nor sit for more than 5 min. The patient did not respond to standard treatments. We prescribed a combination of topical baclofen 5 % and palmitoylethanolamide 400 mg, three times daily. After 3 months her symptoms decreased more than 50 % and sexual intercourse was possible again without pain., Conclusion: Topical baclofen and palmitoylethanolamide can be a viable treatment option in chronic vulvodynia and proctodynia.

Objectives: To identify trends in compounding pharmacies with a focus on women's health and, more specifically, the types and combinations of medications used in the treatment of vulvodynia., Methods: This survey study was conducted with 653 nonchain pharmacies that compound medications. Each pharmacy was asked to complete a 19-item online survey assessing general practice and common compounding indications, focusing on women's health., Results: Of the 653 pharmacies contacted, 200 (31%) responded to our survey. Women's health issues ranked third (19%) among the common indications for compounding, preceded by otolaryngology (30%) and dermatology (28%). Of the medications compounded for women's health, the most common indication was bioidentical hormone therapy (73%) followed closely by vaginal dryness (70%) and low libido (65%). Vulvodynia, or vulvar pain, was the fourth most common indication for compounding medication for women's health issues (29%). Vulvovaginal infections were reported as an indication for compounding medications by 16% of respondents., Conclusions: Vulvovaginal symptoms are a common indication for compounding medications in women's health. Further research in understanding the rationale for using compounded medications, even when standard treatments are available for some of these symptoms (eg, vaginal dryness, vulvovaginal infections), is warranted.

Introduction:   Antidepressants have often been recommended as a potential treatment for the management of vulvodynia. However, review of the evidence supporting this recommendation has not been systematically assessed., Aim:   To evaluate the efficacy of antidepressant pharmacotherapy in the treatment of vulvodynia., Main Outcome Measures:   An assessment of the methodological quality of published reports addressing the utility of antidepressants in the treatment of vulvodynia was undertaken. Several secondary outcomes generated in the existing literature were also examined., Methods:   A comprehensive search of the available literature was conducted., Results:   The search yielded 13 published reports, i.e., 2 randomized controlled trials, 1 quasi-experimental trial, 7 non-experimental studies, and 3 case reports. A number of methodological shortcomings were identified in several of the reports with respect to study design including lack of clear inclusion/exclusion criteria, small sample sizes, lack of comparison groups, insufficient blinding, among others. The vast majority of studies utilized tricyclic antidepressants (TCAs). Evidence supporting the benefits of TCAs studied to date was limited, i.e., based largely upon descriptive reports but unsubstantiated by randomized controlled trials. There were no systematic investigations into the comparative efficacy of different antidepressant classes in the treatment of vulvodynia., Conclusion:   There is insufficient evidence to support the recommendation of antidepressant pharmacotherapy in the treatment of vulvodynia. Although some vulvodynia-afflicted patients derive symptom relief from antidepressants, additional research is required to identify those characteristics that would predict those patients for whom antidepressants are more likely to be effective., (© 2012 International Society for Sexual Medicine.)

Introduction: Few randomized controlled trials (RCTs) have been conducted to establish evidence-based management protocols for provoked vestibulodynia (PVD), a chronic vulvar pain condition affecting approximately 14 million women in the U.S. We describe the rationale and design of an NIH funded multicenter clinical trial utilizing an extended release formulation of gabapentin (G-ER), an intervention that preliminary data suggest may be efficacious for this condition., Objectives: 1) to determine if pain from tampon insertion (primary outcome measure) is lower in PVD patients when treated with G-ER compared to when treated with placebo and 2) to determine if G-ER reduces vulvar mechanical hyperalgesia, vaginal muscle pain to palpation, the number and intensity of somatic tenderpoints, spontaneous and provoked pain to intradermal capsaicin with an accompanying increase in cardiac beat-to-beat variability and to identify mechanistically-based PVD subtypes. Additional outcomes include subject reported intercourse pain and summative 24-hour pain., Methods: This 16-week, randomized, double-blind, placebo-controlled, crossover study will enroll 120 women 18 years and older who report tenderness localized to the vulvar vestibule, pain with tampon insertion, and, when sexually active, insertional dyspareunia. Electronically entered daily diaries will be used to determine if pain is lower in PVD subjects when treated with G-ER (up to 3000 mg/d) compared to when treated with placebo. Psychophysiological measures will be obtained at baseline and after 2 weeks at the maximum tolerated dose., Conclusion: We will conduct the first multicenter RCT to confirm efficacy of an agent that is currently used in clinical practice for treating PVD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Anticonvulsant therapy has occasionally been recommended to treat vulvodynia. However, convincing evidence to support this therapeutic option is lacking. The goal of this study was to critically review studies published on the effectiveness of anticonvulsants for the treatment of vulvodynia. Evaluation of the methodological quality of relevant publications was the main outcome measure. MEDLINE, PubMED and Cochrane were used to identify studies published in English between January 1999 and February 2013. Searches were performed between December 2012 and February 2013. Articles were appraised with the Oxford Centre for Evidence-Based Medicine - Levels of Evidence. Eight relevant studies were identified: two case reports, three retrospective studies, two non-randomized prospective studies and one open-label pilot trial study. Gabapentin formed the main focus (87.5%) to reduce vulvar pain; success rates ranged from 50 to 82%. Lamotrigine was used in one study (12.5%) to relieve symptoms; satisfaction was reported in 82%. These results seem promising, but the majority of studies have several methodological weaknesses regarding sample size and design. Insufficient evidence was available to recommend anticonvulsants for the treatment of vulvodynia. Further studies are necessary with double-blind, randomized-controlled designs to investigate the effectiveness of anticonvulsant therapy for vulvodynia.