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.

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.

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.

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.

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.

Individualized multidisciplinary therapy for vulvodynia.

OBJECTIVE: The main objective of this review was to develop strategies for individualizing multidisciplinary therapy for vulvodynia. METHODS: We conducted two literature searches; the first one focused on clinical trials assessing vulvodynia treatments published after the recommendations of the expert committee of the Fourth International Consultation on Sexual Medicine. The second search targeted studies identifying predictive factors and mediators of vulvodynia treatments, published from the earliest date to October 2022. RESULTS: Based on data from 55 relevant studies, we developed models of individualized multidisciplinary therapy targeting groups of women less responsive to multidisciplinary therapy (characterized by women with higher vulvar pain intensity, impaired sexual functioning, and vulvodynia secondary subtype) and to physical therapy, as an isolated treatment (characterized by women with increased pelvic floor muscle tone and vulvodynia primary subtype). Each individualized multidisciplinary therapy model comprises three components: psychotherapy, medical care, and physical therapy. These components provide distinct therapeutic modalities for distinct subgroups of women with vulvodynia; the women subgroups were identified according to the characteristics of women, the disease, partners, and relationships. Additionally, for women with provoked vestibulodynia who exhibit less benefits from vestibulectomy (such as those with higher levels of erotophobia, greater vulvar pain intensity, and the primary subtype) and encounter resistance to individualized multidisciplinary therapy, we suggest additional conservative treatments before performing vestibulectomy. CONCLUSION: Our study is a pioneer in the development of models that allow the individualization of multidisciplinary therapy for vulvodynia and represents a significant advance in the clinical practice of gynecologists, physiotherapists, and psychologists.

"Time is on my side". Disease trajectory of vulvodynia: a systematic review with a narrative synthesis.

PURPOSE: The aim of this systematic review was to shed light on the disease-trajectory of vulvodynia and identify potential risk factors which may affect such trajectory. METHODS: We searched Pubmed to identify articles providing evidence on vulvodynia trajectory (i.e., remission, relapse or persistence rates) with a minimum follow-up of 2 years. A narrative approach was used for data synthesis. RESULTS: Four articles were included (total participants: 741 women with vulvodynia; 634 controls). At a 2-year follow-up, 50.6% of women reported remission, remission with relapse was observed in 39.7% and persistence throughout time occurred in 9.6%. A decrease in pain was observed in 71.1% of patients at a 7-year follow-up. Mean pain scores and depressive symptoms resulted lower at 2-year follow-up, whereas sexual function and satisfaction were increased. Factors associated with remission of vulvodynia were greater couple cohesion, decreased reporting of pain after intercourse and lower levels of worst pain. Risk factors for symptom persistence included marriage, more severe pain ratings, depression, pain with partner touch, interstitial cystitis, pain with oral sex, fibromyalgia, older age and anxiety. Recurrence was associated with: longer duration of pain, more severe ratings of the worst pain ever and pain described as provoked. CONCLUSIONS: Symptoms of vulvodynia seem to improve over time, regardless of treatment. This finding contains a key message for patients and their physicians, considering the deleterious consequences of vulvodynia on women's lives.

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.

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.

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.

Evidence for increased tone or overactivity of pelvic floor muscles in pelvic health conditions: a systematic review.

OBJECTIVE: Pelvic floor muscle tone, which includes active and passive components, is argued to be increased in many pelvic health conditions, including those involving pain. This study systematically reviewed evidence for increased pelvic floor muscle tone in pelvic health conditions. DATA SOURCES: Electronic databases (PubMed, CINAHL, and Embase) were searched up to May 31, 2021. The search strategy included variants of pelvic and/or floor, muscle, and tone using keywords and Medical Subject Headings (MeSH) terms. STUDY ELIGIBILITY CRITERIA: Studies were included if they investigated increased tone of the pelvic floor muscle and reported measures of active or mechanical properties of the pelvic floor muscle in humans with any pelvic health condition, including pain, bowel, urogenital, or sexual dysfunctions. Studies of any design were included, except systematic and narrative reviews. Reference lists of studies, reviews, and book chapters were searched for additional studies. METHODS: Data were extracted using a standardized form, including measurement tool and outcome measure. Risk of bias was analyzed using a modified ROBINS-I (Risk of Bias In Non-randomized Studies - of Interventions) tool, and a score was allocated to determine whether the study provided "convincing" interpretation (comparison with condition-free control group, valid measure, no application issues). RESULTS: In total, 151 studies were included, reporting 8 different tools (electromyography, dynamometry, manometry, digital palpation, defecography, ultrasound, magnetic resonance imaging, other). The most common pelvic health condition was pelvic pain (n=16 conditions), followed by bowel and urogenital conditions. Most studies (57%) were cross-sectional. A healthy control group was infrequently included for comparison (27%). Unvalidated methods or methods applied in a manner that precluded convincing interpretation were common (94%). Of the 15 measurement tools that provided convincing evidence, 10 demonstrated greater tone in a pelvic health condition (all pain) compared with controls, and 5 showed no difference. CONCLUSION: Despite the large literature, few studies provide convincing evidence for increased tone/overactivity of pelvic floor muscles in pelvic health conditions. Interpretation is hampered by design and measurement issues. Terminology was often inaccurate. Few studies investigate male, transgender, and pediatric groups.

Validation of the 'Pelvic Pain Map': a new self-assessment tool for chronic pelvic pain localisation.

OBJECTIVE: To develop and validate the Pelvic Pain Map to fill a gap in the need for a localised body map of the pelvic region. PATIENTS AND METHODS: The Pelvic Pain Map incorporated input from 12 chronic pelvic pain experts across the United States, as well as patient feedback to assess face validity. Finalised diagrams are single, front-facing images of the male and female pelvis that incorporate both abdominal and perineal views. Assessment of test-retest reliability and construct (convergent and discriminant) validity was carried out on a retrospective cohort of patients with chronic pelvic pain syndrome (CPPS) who completed the maps from January 2022 to May 2022. Other measures used in the validation process consisted of the male and female forms of the Genitourinary Pain Index (GUPI) and the short form (six item) of the Pain Catastrophising Scale (PCS-6). RESULTS: Test-retest for individual map zones demonstrated moderate to excellent reliability (Cohen's kappa coefficients ranging from 0.28 to 0.64) and for total map zones demonstrated excellent reliability (intraclass correlation coefficient = 0.90). Convergent validity for individual map zones with location descriptors from the GUPI was strong (phi coefficients ranging from 0.26 to 0.79) and for total map zones was moderate (Spearman's correlation coefficient = 0.56). Discriminant validity for total map zones with separate, but related constructs from the GUPI and PCS-6 was weakly positive (Spearman's correlation coefficients ranging from 0.27 to 0.32). CONCLUSION: This study suggests that the Pelvic Pain Map is a valid and reliable tool for assessing location of pain in patients with CPPS. Our findings highlight the potential utility of the Pelvic Pain Map in guiding treatment selection and monitoring therapeutic response in patients with chronic pelvic pain.

A scoping review: the psychosocial barriers that exist for people with vulvodynia.

BACKGROUND: Vulvodynia, including generalized vulvodynia and vestibulodynia, affects at least 8% to 16% of people with a vulva and may have a negative impact on one's quality of life, psychological health, interpersonal relationships, and individual behaviors. AIM: The aim of this scoping review is to synthesize and analyze the emerging literature of vulvodynia research while determining what psychosocial barriers exist for people with vulvodynia. METHODS: A rigorous literature search was completed in 6 databases: PubMed, CINAHL, Embase, Web of Science, APA PsycInfo, and Academic Search Premier. Key terms and subject headings, including Medical Subject Headings, were used to systematically search these databases. Two reviewers were utilized to assess the reference list and reduce bias. OUTCOMES: A total of 671 articles were discovered during the search, which was narrowed down to 73 that included at least 1 psychosocial barrier that patients experience in the United States and Canada. RESULTS: The findings of the literature search revealed the various psychosocial barriers that patients commonly face: pain, anxiety, depression, catastrophization, fear, lack of self-efficacy, low desire and arousal, negative body image, stigma, distress, posttraumatic stress disorder, child maltreatment and abuse, mistrust, invalidation and isolation, low levels of self-compassion, negative partner support, low relationship satisfaction, lack of physical affection, emotional regulation, and avoidance and lack of approach goals. In addition to psychosocial barriers, structural determinants and environmental barriers-such as delayed diagnosis, low health literacy, cost, transportation, and racial disparities-adversely affected individuals with vulvodynia. CLINICAL IMPLICATIONS: This review should serve as a guide for researchers, medical providers, and program developers to understand all the barriers that patients may face. STRENGTHS AND LIMITATIONS: This review comprehensively highlights existing psychological barriers while promoting structural and environmental barriers that people with vulvodynia face. More research and greater emphasis on the underlying physical conditions that contribute to vulvodynia are needed to effectively educate providers and patients on vulvar pain conditions. CONCLUSIONS: This scoping review highlights the numerous barriers faced by patients with vulvodynia and serves to improve education for patients and providers to achieve earlier diagnoses and better patient outcomes.

Sexual communication patterns in couples with vulvodynia-a case-control behavioral observation study.

BACKGROUND: Sexual communication is a common target in psychological treatments for vulvodynia, and associations with sexual function and distress, as well as pain intensity, have been demonstrated. However, structured observations of the communication patterns of couples with vulvodynia are lacking, as these are needed to guide treatment efforts. AIM: To explore (1) the sexual communication patterns in couples with vulvodynia in terms of observed communication quality (operationalized as validating and invalidating responses), self-reported sexual assertiveness, and self-disclosure and (2) associations between sexual communication quality and pain intensity. METHODS: In a case-control design with within- and between-group comparisons, 62 couples engaged in videotaped discussions about their sexual relationship. Trained coders assessed the discussions by rating sexual communication (validation and invalidation) according to a structured behavioral coding scheme. Group differences in sexual communication quality were examined with parametric and nonparametric tests. Dyadic associations among observed communication quality, self-rated sexual assertiveness, and self-disclosure were examined within the actor-partner interdependence model. Multiple regression was used to test the predictive value of partners' validation/invalidation on the pain intensity of the women with vulvodynia. OUTCOMES: Observed communication quality (ie, validation and invalidation), self-reported sexual assertiveness, self-disclosure, and pain intensity. RESULTS: Partners of women with vulvodynia were more invalidating toward their partners than those of women without pain. There were no significant differences in validating/invalidating communication between women in the 2 groups or in validation between partners. Partners' validating communication were significantly associated with women's lower pain intensity. The sexual communication patterns differed between couples with and without vulvodynia, and the associations between validating/invalidating responses and sexual assertiveness were stronger in the vulvodynia group than in the group without pain. Results on validation/invalidation and self-disclosure were inconclusive. CLINICAL IMPLICATIONS: The results indicate a need to direct treatment interventions toward couples' sexual communication quality (ie, levels of validation and invalidation). STRENGTHS AND LIMITATIONS: Strengths include systematic behavioral coding and dyadic analyses. Limitations include the cross-sectional design and self-selection of participants. CONCLUSION: This study demonstrated sexual communication patterns specific to couples with vulvodynia, and we conclude that validation and invalidation are important components of the sexual communication of couples with vulvodynia as they relate to sexual assertiveness, women's self-disclosure, and pain intensity.

Exploring the health care experiences of women diagnosed with vulvodynia.

BACKGROUND: Although seeking diagnosis and treatment for chronic pain should be straightforward, this is not typically the case for those living with vulvodynia, who often describe it as a battle, frequently involving misdiagnosis, dismissal, and gender-based discrimination. AIM: This study explored the health care experiences of women living with vulvodynia in the United Kingdom. METHODS: As they are less explored in literature, experiences postdiagnosis and across varying health care settings were specifically considered. Interviews were conducted with 6 women aged 21 to 30 years to explore their experiences when seeking help for vulvodynia. OUTCOMES: Through interpretative phenomenological analysis, 5 themes emerged: the impact of diagnosis, patients' perception of health care, self-guidance and lack of direction, gender as a barrier to effective care, and a lack of consideration of psychological factors. RESULTS: Women often experienced difficulties before and after diagnosis, and many felt that their pain was dismissed and ignored due to their gender. Pain management was felt to be prioritized by health care professionals over well-being and mental health. CLINICAL IMPLICATIONS: There is a need for further exploration of gender-based discrimination experiences among patients with vulvodynia, health care professionals' perceptions of their capabilities in working with such patients, and the impact of improving professionals' training in working with these patients2. STRENGTHS AND LIMITATIONS: Health care experiences after diagnosis are rarely examined within literature, with studies predominantly focusing on experiences surrounding diagnosis, intimate relationships, and specific interventions. The present study provides an in-depth exploration of health care experiences through participants' lived experiences and gives insight into an underresearched area. Women with negative experiences of health care may have been more likely to participate than those with positive experiences, which may have resulted in their overrepresentation. Furthermore, participants were predominantly young White heterosexual women, and almost all had comorbidities, further limiting generalizability. CONCLUSION: Findings should be used to inform health care professionals' education and training to improve outcomes for those seeking care for vulvodynia.

Are pelvic pain and increased pelvic floor muscle tone associated in women with persistent noncancer pelvic pain? A systematic review and meta-analysis.

BACKGROUND: The association between pelvic pain and pelvic floor muscle (PFM) tone in women with persistent noncancer pelvic pain (PNCPP) is unclear. AIM: To synthesize the evidence of the association between pelvic pain and PFM tone in women with PNCPP. METHODS: A systematic review was conducted via MEDLINE, Emcare, Embase, CINAHL, PsycINFO, and Scopus to identify relevant studies. Studies were eligible if pelvic pain and PFM tone outcome measures were reported among women aged >18 years. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess study quality. Studies were pooled by assessment of PFM tone via a random effects model. Associations between the presence of pelvic pain and PFM tone were assessed with odds ratio (OR), while linear associations were assessed with Pearson or Spearman correlation. OUTCOMES: Pelvic pain measures (intensity, threshold, and frequency) and resting PFM tone in women with PNCPP, as evaluated by any clinical assessment method or tool. RESULTS: Twenty-four studies were included in this review. The presence of pelvic pain was significantly associated with increased PFM tone as assessed by digital palpation (OR, 2.85; 95% CI, 1.66-4.89). Pelvic pain intensity was inversely but weakly associated with PFM flexibility when evaluated through dynamometry (r = -0.29; 95% CI, -0.42 to -0.17). However, no significant associations were found between pelvic pain and PFM tone when measured with other objective assessment methods. CLINICAL IMPLICATIONS: Pelvic pain and increased PFM tone may not be directly associated; alternatively, a nonlinear association may exist. A range of biopsychosocial factors may mediate or moderate the association, and clinicians may need to consider these factors when assessing women with PNCPP. STRENGTHS AND LIMITATIONS: This review was reported according to the PRISMA guidelines. All possible findings from relevant theses and conference abstracts were considered in our search. However, nonlinear associations between pelvic pain and increased PFM tone were not assessed as part of this review. CONCLUSION: Pelvic pain may be linearly associated with increased PFM tone and decreased PFM flexibility when measured with digital palpation or dynamometry; however, this association was not observed when other aspects of PFM tone were assessed through objective methods. Future studies are required using robust assessment methods to measure PFM tone and analyses that account for other biopsychosocial factors that may influence the association.

Pelvic mapping to explore patterns of chronic pelvic pain.

PURPOSE: Chronic pelvic pain syndromes (CPPS) are commonly encountered by urologists and urogynecologists and pose diagnostic and therapeutic challenges. Body maps have been helpful adjuncts to verbal descriptions of pain and may serve a role in phenotyping what is known to be a heterogeneous patient population. The aim of this study was to assess whether patterns of pain as marked on a body map of the pelvis exist among common CPPS diagnoses. The secondary aim was to investigate the association between the total number of pain locations marked on the map and clinical indices in patients with 1 to 3 CPPS diagnoses. MATERIALS AND METHODS: Data was collected on patients who visited the Northwell Health Pelvic Pain Treatment Center (PPTC) from January to May 2022 and were diagnosed with at least one of four major CPPS diagnoses: interstitial cystitis/bladder pain syndrome (IC/BPS), pelvic floor myalgia (PFM), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and vulvodynia. Demographic data as well as survey data from pelvic pain maps, Genitourinary Pain Index (GUPI) forms, and the short form-6 of the Pain Catastrophizing Scale (PCS-6) were recorded. Descriptive statistics among CPPS groups and Pearson correlations among the number of CPPS diagnoses were computed. RESULTS: One hundred seventy females and 125 males with CPPS were included in the study. Significant cross-over in mapping patterns was notable between IC/BPS and PFM groups, both most commonly marking "abdomen" and "genital" regions. The most distinct pattern of pain was seen in patients with CP/CPPS and in patients with vulvodynia. Among the total sample, as the mean number of pain locations marked within the pelvis increased, GUPI and PCS scores increased (p < 0.05). As the number of CPPS diagnoses increased, the strength of the relationship independently increased. CONCLUSIONS: Pelvic body mapping demonstrated that different forms of CPPS displayed different distributions of pain, but mapping was not predictive of any diagnostic group. Nevertheless, the pelvic body map proved useful in identifying precise locations of pain and may help uncover regions of pain that cannot be easily communicated. The total number of pain sites marked appeared to correlate with worse clinical features.

Does the addition of electrical stimulation or kinesiotherapy improve outcomes of amitriptyline treatment for women with vulvodynia? A randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia. METHODS: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat. RESULTS: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04). CONCLUSION: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up.

"It's all my fault": a qualitative study of how heterosexual couples experience living with vulvodynia.

INTRODUCTION: Vulvodynia, a chronic genital pain disorder with a high lifetime prevalence among women, has a significant negative impact on both women and their partners. Although there is a growing body of literature on the experiences of women with vulvodynia, there has been little research on the condition's implications for partners and romantic relationships. The aim of this study is to explore how heterosexual couples experience living with vulvodynia. MATERIAL AND METHODS: Eight Norwegian women diagnosed with vulvodynia by gynecologists were recruited with their partners (couples aged 19-32 years). Data was collected via individual semi-structured interviews and analyzed using inductive thematic analysis. RESULTS: Three main themes were identified in the analysis: Mysterious disorder, Social exclusion and Sexual expectations. The results show that the couples struggle with understanding the pain, as well as navigating their social and sexual lives. We discuss these findings in light of a new theoretical model: the fear-avoidance-endurance model of vulvodynia. CONCLUSIONS: Heterosexual couples living with vulvodynia experience communication difficulties with partners, health professionals, and their social network. This sustains avoidance and endurance behavior, increasing pain and dysfunction over time and giving rise to feelings of powerlessness and loneliness. Social expectations regarding male and female sexuality also promote guilt and shame for both parties in couples affected by vulvodynia. Our results suggest that heterosexual couples living with vulvodynia, as well as health professionals treating them, should be helped to communicate more effectively in order to break vicious circles of maladaptive avoidance and endurance behavior.

Obstetric outcomes in women with vulvodynia or vaginismus.

PURPOSE: Vulvodynia and vaginismus are common chronic vulvar pain disorders for which there is a paucity of literature on pregnancy outcomes of affected women. The study objective was to evaluate the associations between vulvodynia and vaginismus and obstetric outcomes. METHODS: We performed a retrospective cohort study including all birth-related admissions from 1999 to October 2015 extracted from the Healthcare Cost and Utilization Project-National Inpatient Sample from the United States. Women with vulvodynia or vaginismus were identified using the appropriate ICD-9 codes. Multivariate logistic regression models, adjusted for baseline maternal characteristics, were performed to evaluate the effect of vulvodynia and vaginismus on obstetrical and neonatal outcomes. RESULTS: A total of 879 obstetrical patients with vulvodynia or vaginismus were identified in our cohort of 13,792,544 patients admitted for delivery in US hospitals between 1999 and 2015, leading to an overall prevalence of 6 cases per 100,000 births. Between 1999 and 2015, the annual prevalence of vulvodynia or vaginismus rose from 2 to 16 cases per 100,000. Vulvodynia and vaginismus were associated with increased risks of eclampsia, chorioamnionitis, post-term pregnancy, cesarean delivery, instrumental vaginal delivery, blood transfusions, prolonged hospital stays, congenital anomalies and intrauterine growth restriction. CONCLUSION: Vulvodynia and vaginismus in pregnancy appears underreported in pregnancy compared to reported population rates. Prevalence of reporting seems to have increased in the last decades and is associated with increased risks of maternal and newborn morbidities. Obstetrical caregivers should be aware of the underreporting of these conditions and the associated adverse effects when counseling obstetrical patients.