Psychiatric morbidity across the life course and provoked vulvodynia: is it dependent upon the presence of non-stress-related immune dysfunction?

BACKGROUND: Vulvodynia impacts up to 8% of women by age 40, and these women may have a more compromised immune system than women with no vulvar pain history. AIM: Given that psychiatric morbidity is associated with vulvodynia and is known to activate immune inflammatory pathways in the brain and systemically, we sought to determine whether the association between psychiatric morbidity and vulvar pain was independent of or dependent upon the presence of immune-related conditions. METHODS: Women born in Sweden between 1973 and 1996 with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) diagnosed between 2001 and 2018 were matched to two women from the same birth year with no vulvar pain. International Statistical Classification of Diseases and Related Health Problems (ICD-9 or -10 codes) were used to identify women with a history of depression, anxiety, attempted suicide, neurotic disorders, stress-related disorders, behavioral syndromes, personality disorders, psychotic disorders, or chemical dependencies, as well as a spectrum of immune-related conditions. The Swedish National Prescribed Drug Register was used to identify women with filled prescriptions of antidepressants or anxiolytics. OUTCOMES: Vulvodynia, vaginismus, or both were outcomes assessed in relation to psychiatric morbidity. RESULTS: Women with vulvodynia, vaginismus, or both, relative to those without vulvar pain, had adjusted odds ratios between 1.4 and 2.3, with CIs highly compatible with harmful effects. When we assessed women with and those without a lifetime history of immune-related conditions separately, we also observed elevated odds ratios in both groups for mood, anxiety, and neurotic and stress disorders. CLINICAL IMPLICATIONS: Documenting psychiatric impairment as a cause or consequence of vulvodynia is critical in clinical practice because psychiatric conditions may impact treatment efficacy. STRENGTHS AND LIMITATIONS: Strengths of this study include a data source that represents the entire population of women in Sweden that is known to be highly accurate because Sweden provides universal healthcare. Limitations include difficulty in making an accurate assessment of temporality between psychiatric morbidity and the first onset of vulvar pain. In addition, because Swedish registry data have limited information on lifestyle, behavioral, and anthropomorphic factors such as smoking, diet, physical activity, and obesity, these conditions could not be assessed as confounders of psychiatric morbidity and vulvar pain. CONCLUSIONS: Immune pathways by which women with psychiatric conditions increase their risk of vulvar pain could be independent from other immune pathways.

Unsupervised Machine Learning Reveals a Vulvodynia-Predominant Subtype in Bladder Pain Syndrome/Interstitial Cystitis.

Background Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic condition characterized by pelvic pain and urinary symptoms. Despite its significant impact on patients' quality of life, the heterogeneity of BPS/IC symptoms and the presence of comorbidities such as vulvodynia may not be adequately captured by validated questionnaires. Identifying vulvodynia in BPS/IC patients is crucial for providing appropriate treatment options. This study aimed to identify subtypes of BPS/IC patients using unsupervised machine learning and to investigate the prevalence of vulvodynia in each subtype. Methods We conducted a prospective cross-sectional study of 123 BPS/IC patients and 64 age-matched controls. Hierarchical clustering was performed using data from validated questionnaires, including the Numerical Rating Scale-11, Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency scores, Overactive Bladder Questionnaire Short Form (OABq SF), Overactive Bladder Symptom Score (OABSS), and Pelvic Floor Distress Inventory-20. The optimal number of clusters was determined using the elbow method, and the characteristics of each cluster were analyzed. All participants underwent a vulvodynia swab test to assess vulvodynia symptoms. Results Unsupervised machine learning revealed three distinct clusters of BPS/IC patients. Clusters 0 and 2 differed significantly, with Cluster 2 characterized by significantly higher vulvodynia scores compared to other clusters (P < 0.001). In contrast, Cluster 2 had lower bladder pain scores (ICSI and ICPI) and overactive bladder symptom scores (OABq SF and OABSS) compared to other clusters. Clusters 0 and 1 were characterized by a predominance of bladder pain and urinary frequency symptoms, with Cluster 0 exhibiting more severe symptoms. Conclusions Our study identified distinct subtypes of BPS/IC patients using unsupervised machine learning, with Cluster 2 representing a vulvodynia-predominant subtype. This finding, along with the potential of targeted therapies such as non-ablative erbium YAG laser for vulvodynia, underscores the importance of assessing extravesical symptoms, particularly vulvodynia, for the diagnosis and treatment of BPS/IC. A tailored approach, including laser therapy for vulvodynia-predominant patients, may be necessary for optimal management of BPS/IC. The vulvodynia swab test plays a crucial role in assessing vulvodynia symptoms, underlining the limitations of validated questionnaires in capturing the full spectrum of BPS/IC symptoms. A comprehensive evaluation of patients, including the vulvodynia swab test, is essential for accurate subtyping and management of BPS/IC. Further research with larger sample sizes and investigation of the relationship between identified subtypes and other clinical data is warranted to advance our understanding and management of BPS/IC.

Does One Measure Fit All? The Role of Experimentally Induced Pain Tests in the Assessment of Women with Provoked Vestibular Pain.

Purpose: A diagnostic algorithm was recently suggested to address the underlying mechanisms of provoked-vestibulodynia (PVD). It delineates four subgroups (Hormonal-associated, Augmented-anterior, Hymenal-associated and Hypertonicity-associated), each manifesting a distinctive vulvar pain-hypersensitivity regarding location (circumferential vs posterior-only vestibulodynia) and pain characteristics. We aimed to explore the significance of various experimentally induced vulvar pain measures in the manifestation of pain hypersensitivity in each subgroup. Methods: Women with PVD (n = 113) and 43 controls reported pain intensity provoked during vaginal penetration and tampon insertion. Vestibular tenderness (anterior and posterior) was assessed by Q-tip test, and pressure stimulation delivered to the puborectalis assessed muscle tenderness. Pain thresholds were measured using a vulvar-algesiometer. These measures were compared between patients and controls and among the PVD subgroups. Correlations between the clinical and experimentally induced-pain measures were assessed. Finally, to address whether the association between experimentally induced-pain measures and dyspareunia severity is mediated by hypertonicity, the conditional indirect effect was analyzed in each subgroup. Results: Compared to controls, augmented vulvar pain-hypersensitivity and hypertonicity were observed among patients (p < 0.001). ANOVA revealed no subgroup differences in dyspareunia severity. Nevertheless, some experimentally induced-pain measures were differently correlated with dyspareunia intensity in each subgroup, allowing discrimination of subgroups according to the unique findings of vulvar pain-hypersensitivity. The degree of pelvic floor muscle-hypertonicity mediated the association between vulvar pain-hypersensitivity and dyspareunia severity, emphasizing the key role of hypertonicity in distinguishing between subgroups. Conclusion: The findings offer more evidence of variations among PVD subtypes, demonstrating that insertional dyspareunia may originate from dissimilar alterations in the mucosal and muscular tissues. The results also emphasize the significance of utilizing a wide battery of tests to capture different experimentally induced-pain measures, revealing the unique patterns of vulvar pain-hypersensitivity in each subgroup.

Inflammation-induced mast cell-derived nerve growth factor: a key player in chronic vulvar pain?

Provoked vulvodynia (PV) is characterized by localized chronic vulvar pain. It is associated with a history of recurrent inflammation, mast cell (MC) accumulation, and neuronal sprouting in the vulva. However, the mechanism of how vulvar-inflammation promotes neuronal sprouting and gene-expression adaptation in the spinal cord, leading to hypersensitivity and painful sensations, is unknown. Here, we found that vulvar tissue from women with PV (n=8) is characterized by MC accumulation and neuronal sprouting compared to women without PV (n=4). In addition, we observed these changes in an animal study of PV. Thus, we found that repeated vulvar zymosan-inflammation challenges lead to long-lasting mechanical and thermal vulvar hypersensitivity, which was mediated by MC accumulation, neuronal sprouting, overexpression of the pain channels (TRPV1 and TRPA1) in vulvar neurons, as well as a long-term increase of gene expression related to neuroplasticity, neuroinflammation, and nerve growth factor (NGF) in the spinal cord/DRG(L6-S3). However, regulation of the NGF pathway by stabilization of MC activity with ketotifen fumarate (KF) during vulvar inflammation attenuated the local increase of NGF and histamine, as well as the elevated transcription of pro-inflammatory cytokines, and NGF pathway in the spinal cord. Additionally, KF treatment during inflammation modulates MC accumulation, neuronal hyperinnervation, and overexpression of the TRPV1 and TRPA1 channels in the vulvar neurons, consequently preventing the development of vulvar pain. A thorough examination of the NGF pathway during inflammation revealed that blocking NGF activity by using an NGF-non-peptide-inhibitor (Ro08-2750) regulates the upregulation of genes related to neuroplasticity, and NGF pathway in the spinal cord, as well as modulates neuronal sprouting and overexpression of the pain channels, resulting in a reduced level of vulvar hypersensitivity. On the other hand, stimulation of the NGF pathway in the vulvar promotes neuronal sprouting, overexpression of pain channels, and increase of gene expression related to neuroplasticity, neuroinflammation, and NGF in the spinal cord, resulting in long-lasting vulvar hypersensitivity. In conclusion, our findings suggest that vulvar allodynia induced by inflammation is mediated by MC accumulation, neuronal sprouting, and neuromodulation in the vulvar. Additionally, chronic vulvar pain may involve a long-term adaptation in gene expression in the spinal cord, which probably plays a critical role in central sensitization and pain maintenance. Strikingly, regulating the NGF pathway during the critical period of inflammation prevents vulvar pain development via modulating the neuronal changes in the vestibule and spinal cord, suggesting a fundamental role for the NGF pathway in PV development.

Role of sexuality in women with chronic pain: Results from an Italian cross-sectional study on chronic headache, fibromyalgia, and vulvodynia.

Background/objectives: To compare sexual functioning, genital pain, and satisfaction among women diagnosed with various Chronic pain (CP) conditions. Additionally, it seeks to explore the role of sexual factors in predicting levels of central sensitization (indicative of CP-related mental and physical distress), physical, and mental quality of life (QoL) for each condition individually. Methods: From April 2023 to January 2024, 1006 women categorized into five groups (Chronic Headache - CH; Fibromyalgia - FM, Vulvodynia - VU, Comorbidity group - CO, and Healthy Controls - HC) completed an online protocol. Results: All groups reported sexual impairment: VU group exhibited the highest genital pain prevalence (97.93 %), followed by CO (74.29 %) and FM (55.91 %). ANCOVAs indicated lower sexual functioning scores for FM, VU, and CO compared to HC and CH. VU and CO reported lower satisfaction scores than other groups. Genital pain emerged as the primary predictor of central sensitization across all groups except controls. Regarding mental QoL, sexual satisfaction was significant for CH and CO, while genital pain and sexual satisfaction were significant for VU. Conclusion: This study emphasizes the importance of integrating genito-pelvic pain assessment and addressing related sexual difficulties in CP diagnostics and care to enhance overall well-being and QoL.

A Hypothesis for Anatomical Pathways of Chronic Pelvic Pain of "Unknown Origin".

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disabling bladder condition. ESSIC, the IC/BPS society defines two types of IC/BPS: with Hunner's lesion (HL) and without. Pathogenesis is stated as unknown, with no cure possible. Scheffler in 2021 reported cystoscopically validated cure of HL IC/BPS by repair of uterosacral ligaments (USLs) and in 2022, Goeschen reported non-HL IC/BPS cure in 198 women following USL repair. Both Scheffler and Goeschen hypothesized IC/BPS may be a phenotype of the Integral Theory's Posterior Fornix Syndrome "PFS" (chronic pelvic pain, OAB, and emptying dysfunctions) and therefore potentially curable. SUMMARY: The hypothesis explores whether visceral plexuses (VPs), due to weakened USLs support, serve as a primary source of pelvic pain impulses, leading to development of an inflammatory condition - for example, IC/BPS, a chronic inflammatory condition, which shares similarities with vulvodynia and complex regional pain syndrome (CRPS). According to our hypothesis, such conditions involve axon reflexes. Stimuli such as gravity applied to unsupported nerve branches within the visceral pelvic plexus, trigger centrally propagating impulses, which then progress antidromally to influence innervated tissues through cytokine release and nociceptor stimulation, perpetuating inflammatory processes at the end organs, and pain perception. KEY MESSAGES: The hypothesis raises the question, "are IC/BPS, vulvodynia, other pain sites, even nonbacterial "chronic prostatitis" in the male, different phenotypes of the chronic pelvic pain syndrome which includes PFS. If so, the hypothesis opens several new research directions and would predict inflammatory findings in tender end organ pain sites.

Development of aids to relieve vulvodynia during the postpartum period.

Postpartum women live with a low quality of life due to pain caused by episiotomy and perineal laceration. In particular, they endure pain when sitting for long periods of time to breastfeed. The purpose of this study is to develop a sitting aid to alleviate postpartum vulvodynia. This study was conducted in the following four phases from July 2017 to May 2019. They are: material selection and molding, cleaning and disinfection testing, pressure distribution measurement testing, and trial testing by postpartum women. The main material was a 100% polypropylene object with a three-dimensional reticular fiber spring structure and fiber density of 3.8 kg/m2. As a result, a sitting aid that withstands washing and disinfection well in the medical field and is breathable. It had moderate resilience and elasticity and reduced pressure on the seating surface for women weighing approximately 45 kg and 55 kg, but we were skeptical about its use for women weighing more than that. The completed sitting aid is noninvasively effective in improving the quality of life of many postpartum women, but the density and thickness of the main material should be reexamined to meet the needs of women in a wider weight range. In addition, a self-administered questionnaire survey of trial users revealed that some women did not experience relief from vulvodynia even after using the sitting aid. Such women also had physical problems such as discomfort in the lower back, difficulty breastfeeding, and difficulty standing up. For women with multiple physical problems, individual causes should be addressed.

Spinal neuronal activity and neuroinflammatory component in a mouse model of CFA-induced vestibulodynia.

Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of vestibulodynia induced by complete Freund's adjuvant (CFA) focusing our investigation on the spinal cord neurons and microglia. We investigated tactile allodynia, spontaneous pain, and depressive-like behavior as key behavioral markers of vestibulodynia. In addition, we conducted in vivo electrophysiological recordings to provide, for the first time to our knowledge, the characterization of the spinal sacral neuronal activity in the L6-S1 dorsal horn of the spinal cord. Furthermore, we examined microglia activation in the L6-S1 dorsal horn using immunofluorescence, unveiling hypertrophic phenotypes indicative of neuroinflammation in the spinal cord. This represents a novel insight into the role of microglia in vestibulodynia pathology. To address the therapeutic aspect, we employed pharmacological interventions using GABApentin, amitriptyline, and PeaPol. Remarkably, all three drugs, also used in clinic, showed efficacy in alleviating tactile allodynia and depressive-like behavior. Concurrently, we also observed a normalization of the altered neuronal firing and a reduction of microglia hypertrophic phenotypes. In conclusion, our study provides a comprehensive understanding of the CFA-induced model of vestibulodynia, encompassing behavioral, neurophysiological and neuroinflammatory aspects. These data pave the way to investigate spinal cord first pain plasticity in vestibulodynia.

Exploring Localized Provoked Vulvodynia: Insights from Animal Model Research.

Provoked vulvodynia represents a challenging chronic pain condition, characterized by its multifactorial origins. The inherent complexities of human-based studies have necessitated the use of animal models to enrich our understanding of vulvodynia's pathophysiology. This review aims to provide an exhaustive examination of the various animal models employed in this research domain. A comprehensive search was conducted on PubMed, utilizing keywords such as "vulvodynia", "chronic vulvar pain", "vulvodynia induction", and "animal models of vulvodynia" to identify pertinent studies. The search yielded three primary animal models for vulvodynia: inflammation-induced, allergy-induced, and hormone-induced. Additionally, six agents capable of triggering the condition through diverse pathways were identified, including factors contributing to hyperinnervation, mast cell proliferation, involvement of other immune cells, inflammatory cytokines, and neurotransmitters. This review systematically outlines the various animal models developed to study the pathogenesis of provoked vulvodynia. Understanding these models is crucial for the exploration of preventative measures, the development of novel treatments, and the overall advancement of research within the field.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

BACKGROUND: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. PUROPOSE: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). RESULTS: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). CONCLUSION: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.

The association between vulvodynia and interstitial cystitis/bladder pain syndrome: A systematic review.

BACKGROUND: Vulvodynia (VVD) is a debilitating chronic vulvar pain significantly affecting patients' quality of life. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and complex illness characterized by an unpleasant sensation related to the filling of the bladder and it strongly impacts patients' lives. The exact mechanisms of the two syndromes remain unknown, but there is an overlap between suspected pathophysiologies. OBJECTIVE: To present an overview of the current research on the association between VVD and IC/BPS. SEARCH STRATEGY: A systematic search of three electronic databases was conducted. Studies examining the correlation between VVD and IC/BPS with male and female patients aged over 18 years were included. SELECTION CRITERIA: Studies assessing the coexistence of VVD and IC/BPS were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers screened the studies for eligibility. Eligible studies were screened for quality. MAIN RESULTS: A total of 13 studies were included in the final review. Among them, 11 presented a positive association between the two syndromes. The studies highlighted that VVD and IC/BPS share common comorbidities and possibly etiopathogenic pathways. CONCLUSION: VVD and IC/BPS are both complex and multifactorial syndromes. This review highlights an association between them, but additional studies on the topic should be conducted for a more precise conclusion.

Efficacy of Rehabilitative Techniques on Pain Relief in Patients With Vulvodynia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia. METHODS: On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale. RESULTS: Meta-analysis showed that all these rehabilitative approaches had an overall effect size of -1.43 (95% CI = -2.69 to -0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = -2.36; 95% CI = -3.83 to -0.89) and extracorporeal shockwave therapy (effect size = -2.94; 95% CI = -4.31 to -1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies. CONCLUSION: Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future. IMPACT: This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia.

Help-seeking experiences and intimate partner support in vulvodynia: A qualitative exploration.

BACKGROUND: Vulvodynia is a poorly understood chronic pain condition characterized by persistent and unexplained pain in the vulva. Given the intimate nature of the pain, partners may play an important role in promoting self-management and help-seeking behaviours among women with vulvodynia. OBJECTIVES: The current study aimed to explore the role of partner support in pain experiences and help-seeking behaviours among women with vulvodynia. DESIGN: A qualitative interpretive design was used. METHODS: Ten women with vulvodynia (M age = 37.9 years) were interviewed using a semi-structured non-directive topic guide. Data were analysed using reflexive thematic analysis. RESULTS: Three themes around help-seeking experiences were constructed from the data: (1) 'It's Been a Battle' - Failed by the Healthcare System; (2) 'It's Just the Vulva' - Dismissed by Healthcare Professionals; and (3) 'I Diagnosed Myself' - The Patient Becomes the Expert. Participants described negative help-seeking experiences characterized by long delays to diagnosis, lack of awareness and understanding from healthcare professionals, minimization of symptoms, and having to advocate for and demand care. A further three themes pertaining to partner support were also developed: (1) 'That Person to Listen to You' - Source of Emotional Support; (2) 'Why Don't You Try This?' - Finding Solutions Together; and (3) 'He Forgets that it's Still There' - Vulvodynia is a Foreign Concept. Partners provided emotional support and showed empathy and understanding, and practical support by accompanying women to medical appointments and help with pain management. However, participants felt partners' understanding of vulvodynia was limited and that this impacted their relationships. CONCLUSIONS: Findings highlight a lack of continuity of care and multidisciplinary approach to treatment, with help-seeking experiences being mainly negative in this sample. Increasing public awareness of vulvodynia and improving healthcare access is crucial to improving physical and psychological outcomes for this group. Partners can play an important role in supporting people with vulvodynia; however, other outlets of support should be further explored.

Understanding How Women with Vulvodynia Seek Help and Get Support from Their PartnersVulvodynia is a condition where women experience persistent and unexplained pain in the vulva. This pain can be quite personal and difficult to deal with. In this study, we wanted to understand how partners of women with vulvodynia help them cope with the pain and seek medical help. We interviewed 10 women with vulvodynia about their experiences of accessing healthcare for their symptoms, and how their partners affected these experiences. Many women faced challenges when seeking medical help, like delays in getting a diagnosis, healthcare professionals not understanding their condition, and their symptoms being downplayed. Women often had to be their own experts and advocate for their care. Partners of these women provided emotional and practical support, like going with them to medical appointments and helping them to manage the pain. However, some women felt their partners did not fully understand vulvodynia, and their worries sometimes strained their relationships. In conclusion, the study showed that there is a need for better healthcare for women with vulvodynia, including more awareness and easier access to treatment. Partners can be supportive, but other forms of support, for example, from friends, family, and other people with experience of vulva pain, should also be explored.

Development of a core outcome set for treatment studies for provoked vestibulodynia.

BACKGROUND: There is an inconsistency in treatment outcomes used in clinical trials for provoked vestibulodynia (PVD), which makes it impossible to compare the effects of different interventions. AIM: In this study, we completed the first step in creating a core outcome set (COS), defining what outcomes should be measured in clinical trials for PVD. METHODS: Identification of outcomes used in studies was done by extracting data from clinical trials in a recently published systematic review and via review of clinical trials for PVD registered on ClinicalTrials.gov. The COS process consisted of 2 rounds of Delphi surveys and a consensus meeting, during which the final COS was decided through a modified nominal group technique. OUTCOMES: Consensus on what outcomes to include in a COS for PVD. RESULTS: Forty scientific articles and 92 study protocols were reviewed for outcomes. Of those, 36 articles and 25 protocols were eligible, resulting in 402 outcomes, which were then categorized into 63 unique outcomes. Participants consisted of patients, relatives/partners of patients, health care professionals, and researchers. Out of 463 who registered for participation, 319 and 213 responded to the first and second surveys, respectively. The consensus meeting consisted of 18 members and resulted in 6 outcomes for the COS to be measured in all treatment trials regardless of intervention: insertional pain (nonsexual), insertional pain (sexual), provoked vulvar pain by pressure/contact, pain-related interference on one's life, pain interference on sexual life, and sexual function. CLINICAL IMPLICATIONS: Critical outcomes to be measured in clinical trials will allow for accurate comparison of outcomes across treatment interventions and provide solid treatment recommendations. STRENGTHS AND LIMITATIONS: The major strengths of the study are the adherence to methodological recommendations and the intentional focus on aspects of diversity of participating stakeholders (eg, status such as patients with lived experience and researchers, inclusiveness with respect to sexual identity), the latter of which will allow for broader application and relevance of the COS. Among the limitations of the study are the low rate of participants outside North America and Europe and the lower response rate (about 50%) for the second Delphi survey. CONCLUSION: In this international project, patients, health care professionals, and researchers have decided what critical outcomes are to be used in future clinical trials for PVD. Before the COS can be fully implemented, there is also a need to decide on how and preferably when the outcomes should be measured.

A survey of patient tolerance and satisfaction with capsaicin for neuroproliferative vestibulodynia.

Background: Topical capsaicin has been used to treat vulvodynia but has been poorly studied for use in neuroproliferative provoked vestibulodynia (PVD); capsaicin decreases allodynia by blocking vanilloid receptors (TRPV1) on C-afferent nociceptors, but the therapy causes discomfort to the point of intolerance in some patients. Aim: The present study evaluated tolerability and efficacy of topical capsaicin to treat neuroproliferative PVD. Methods: Patients with neuroproliferative PVD prescribed 0.025% capsaicin compounded in VersaBase cream were identified through prescription records. Outcome measures included the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale-Revised, and a 22-question questionnaire assessing patient experience and treatment tolerability. Outcomes: Among tolerant patients, capsaicin significantly decreased vestibular pain, but tolerance was highly variable. Results: Twenty-five patients responded to the follow-up questionnaire. The average age at presentation was 30 years (range, 18-52 years). Eighty percent of patients tolerated capsaicin application for the full 20 minutes within a median time of 1 to 2 weeks. Of the 16 patients reporting tolerance to 20-minute application, 12 (60%) experienced improvement in vestibular pain. On an 11-point numeric rating scale, the mean pain score was 8.96 and the median score was 10 with first application. Among all participants, 16 (64%) had reduction in pain during treatment. Fifty-six percent of patients would recommend capsaicin as a treatment for vulvar pain. Qualitative content analysis focused on categories of efficacy, value, and feasibility, which indicated that those able to tolerate the treatment experienced improvement while using the medication. The mean Female Sexual Distress Scale-Revised score was 35.96 at baseline compared with 25.09 at follow-up (P < .0001). On a numeric rating scale, the mean self-reported vulvar pain score was 8.2 at baseline compared with 5.35 when using capsaicin consistently (P < .0001). The mean FSFI pain domain score was 2.45 at baseline compared with 0.98 at follow-up (P = .005). While not statistically significant, the mean total FSFI score was 15.44 at baseline compared with 17.84 at follow-up (P = .3730). Clinical Implications: Capsaicin is helpful for some patients with PVD, but thorough counseling is important because of highly variable tolerance. Strengths and Limitations: Strengths include examination of a poorly studied therapy and inclusion of narrative responses from patients to inform counseling. Limitations include small sample size, retrospective design, and low survey response rate. Conclusion: Patients should be appropriately selected and thoroughly counseled given high levels of intolerance, but capsaicin therapy may be considered for patients with neuroproliferative PVD who have failed conservative treatments and wish to avoid surgery.

Changes in Pelvic Floor Ultrasonographic Features after Flat Magnetic Stimulation in Women with Chronic Pelvic Pain and Levator Ani Muscle Hypertonicity.

Background and Objectives: Chronic pelvic pain (CPP) represents a major public health problem for women with a significant impact on their quality of life. In many cases of CPP, due to gynecological causes-such as endometriosis and vulvodynia-improper pelvic floor muscle relaxation can be identified. Treatment of CPP with pelvic floor hypertonicity (PFH) usually involves a multimodal approach. Traditional magnetic stimulation has been proposed as medical technology to manage muscle hypertonicity and pelvic pain conditions through nerve stimulation, neuromodulation, and muscle relaxation. New Flat Magnetic Stimulation (FMS)-which involves homogeneous rather than curved electromagnetic fields-has the potential to induce sacral S2-S4 roots neuromodulation, muscle decontraction, and blood circulation improvement. However, the benefits of this new technology on chronic pelvic pain symptoms and biometrical muscular parameters are poorly known. In this study, we want to evaluate the modification of the sonographic aspect of the levator ani muscle before and after treatment with Flat Magnetic Stimulation in women with chronic pelvic pain and levator ani hypertonicity, along with symptoms evolution. Materials and Methods: A prospective observational study was carried out in a tertiary-level Urogynaecology department and included women with CPP and PFH. Approval from the local Ethics Committee was obtained before the start of the study (protocol code: MAGCHAIR). At the baseline, the intensity of pelvic pain was measured using a 10 cm visual analog scale (VAS), and patients were asked to evaluate their pelvic floor symptoms severity by answering the question, "How much do your pelvic floor symptoms bother you?" on a 5-answer Likert scale. Transperineal ultrasound (TPU) was performed to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Treatment involved Flat Magnetic Stimulation alone or with concomitant local or systemic pharmacological therapy, depending on the patient's preferences. FMS was delivered with the DR ARNOLD system (DEKA M.E.L.A. Calenzano, Italy). After the treatment, patients were asked again to score the intensity of pelvic pain using the 10 cm visual analog scale (VAS) and to evaluate the severity of their pelvic floor symptoms on the 5-answer Likert scale. Patients underwent TPU to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Results: In total, 11 patients completed baseline evaluation, treatment, and postoperative evaluation in the period of interest. All patients underwent eight sessions of Flat Magnetic Stimulation according to the protocol. Adjuvant pharmacological treatment was used in five (45.5%) patients. Specifically, we observed a significant increase in both ARA and LAMD comparing baseline and post-treatment measurements (p < 0.001). Quality of life scale scores at baseline and after treatment demonstrated a significant improvement in both tools (p < 0.0001). Conclusions: Flat Magnetic Stimulation, with or without adjuvant pharmacological treatment, demonstrated safety and efficacy in reducing pelvic floor hypertonicity, resulting in improvement in symptoms' severity and sonographic parameters of muscular spasm.

Psychosexological correlates of 372 women with vulvodynia, overactive pelvic floor, postcoital cystitis, and interstitial cystitis.

BACKGROUND: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence. AIM: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms. METHODS: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests. OUTCOMES: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis. RESULTS: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women. CLINICAL IMPLICATIONS: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner. STRENGTHS AND LIMITATIONS: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation. CONCLUSION: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission.

Non-ablative Erbium (YAG) and Neodymium (YAG) Laser Treatment for Anal Incontinence and Vaginal Atrophy: A Case Study.

In this case study, a 68-year-old woman with anal incontinence (AI) and vaginal atrophy (VVA), who did not respond to traditional treatments such as pelvic floor exercises or hormone therapy, underwent three sessions of laser treatment using RenovaLase (SP Dynamis; Fotona d.o.o., Ljubljana, Slovenia), which employs non-ablative Erbium:YAG and Neodymium:YAG lasers. Significant improvements were observed in the VVA symptoms, with AI being resolved. The Vaginal Health Index Score increased from 7 points at the initial assessment to 18 points at 12 months after treatment. Similarly, the Cleveland Clinic Florida Fecal Incontinence Score and St. Mark's Incontinence Score, initially at 4 points each, improved to 0 points, indicating resolution of incontinence symptoms. MRI results demonstrated vascular enhancement and growth in the anal sphincter, with the thickness of the internal anal sphincter slightly increasing from initial measurements to a maximum of 0.36 cm, and improvements in resting and squeeze pressures from 42 mmHg to 110 mmHg, respectively. These findings underscore the effectiveness of RenovaLase® laser treatment for VVA and AI symptoms, offering a novel option for pelvic floor health management in postmenopausal women, especially those resistant to the use of artificial devices for anal improvement. In the environment of hormonal decline after menopause, the atrophy of pelvic vessels leads to reduced blood flow. This situation, where a noticeable lack of blood flow occurs during pretreatment of the pelvic vessels, is addressed by laser treatment. This phenomenon has been named "re-canalization." This case suggests the potential of this therapy as an alternative for patients resistant to conventional methods involving the insertion of devices into the anus to improve fecal incontinence. Further research is needed to explore its potential benefits.

Immune Dysregulation, Inflammation in Characterizing Women with Vulvodynia, Depression, and Both.

Background: Depression and vulvodynia are often comorbid. The onset of depression and vulvodynia may be immune and/or stress/environmentally induced. We explored whether vulvodynia, depression, or both occur in response to a Th1-mediated versus Th2-mediated immune response. Materials and Methods: We analyzed data from a case-control study of clinically confirmed vulvodynia and history of depression determined through structured clinical interviews. Immune dysregulation and inflammation were categorized based on the following self-reported conditions: rheumatoid arthritis, Sjogren's disease, scleroderma, systemic lupus erythematosus, inflammatory bowel disease, fibromyalgia, osteoarthritis, polycystic ovarian syndrome, diabetes mellitus, uterine fibroids, asthma, atopic dermatitis, and allergic rhinitis. Logistic regression analyses were adjusted for marital status, body mass index, age, and pack years. Results: Women with systemic immune dysregulation had higher odds of depression (adjusted odds ratio [aOR] = 1.61, confidence interval [95% CI]: 0.65-3.98), vulvodynia (aOR = 2.45, 95% CI: 1.00-5.96), and comorbid depression and vulvodynia (aOR = 4.93, 95% CI: 2.19-11.10) versus neither condition. Women reporting local immune dysregulation had similar odds of depression (aOR = 1.89, 95% CI: 0.99-3.59), vulvodynia (aOR = 2.12, 95% CI: 1.08-4.18), and comorbid depression and vulvodynia (aOR = 1.96, 95% CI: 0.98-3.90). Women with Th2 inflammation had similar odds of depression (aOR = 2.23, 95% CI: 1.05-4.77) and vulvodynia (aOR = 2.56, 95% CI: 1.20-5.49). Women with Th1 or Th2 inflammation had similar odds of comorbid depression and vulvodynia (aOR = 3.03, 95% CI: 1.48-6.19; aOR = 3.14, 95% CI: 1.49-6.60, respectively). Conclusions: Our results suggest that an imbalance of cytokines, indicated by the presence of one or more immune-related health conditions, is associated with an increased risk of vulvodynia and/or depression.

Neodymium Laser Treatment for Overactive Bladder and Vulvodynia in Mayer-Rokitansky-Küster-Hauser Syndrome Patient: A Case Report.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition that affects a small proportion of female individuals at birth, resulting in the absence or underdevelopment of reproductive organs. However, this case report introduces overactive bladder (OAB) and vulvodynia, conditions that have not been previously reported in MRKH patients. The 36-year-old patient began developing breast tissue around the age of 12 but never experienced menstruation. Simultaneously, she started experiencing discomfort in the genital region and frequent urination. These symptoms gradually worsened, making it difficult for her to continue her education, and initially, she was misdiagnosed with a developmental disorder. Typically, the general understanding of MRKH syndrome has focused on reproductive anomalies, but this case underscores its diversity. Diagnostic assessments, including ultrasound, MRI, and various tests, revealed that the patient's severe genital discomfort and urinary symptoms were improved through a specialized Neodymium YAG laser therapy named "PIANO mode," resulting in significant symptom relief and improved quality of life. This report emphasizes the importance of comprehensive and individualized approaches to managing MRKH syndrome. It aims to raise awareness that MRKH syndrome, while often associated with reproductive abnormalities, can also involve related symptoms like OAB and vulvodynia, which can significantly impact daily life.