6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression.

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.

Long-Term Effectiveness of Vestibulectomy for the Treatment of Vulvodynia: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and complication rate of vestibulectomy for vulvodynia. METHODS: A retrospective cohort study in a teaching and university hospital analyzing patients with vulvodynia with insufficient response to conservative treatment who underwent a vestibulectomy. Data from 114 consecutive vestibulectomy procedures done between September 2009 and October 2018 were retrospectively analyzed. All procedures were performed by the same surgeon.The primary outcome was difference in pain scale (6-point Q-tip test, Nociceptive Rating Scale) between preoperative consultation, postoperative visit, and last follow-up consultation. The secondary outcome was surgical complications, such as wound dehiscence and hematoma. RESULTS: Complete data were available for 80 patients. There was a significant reduction in median pain scores of between 65% and 80% on all 6 evaluated vestibular points during Q-tip tests. The median follow-up was 21 months, ranging from 1 to 92 months (interquartile range [IQR]). Overall, 75% of patients needed no further treatment at the end of the follow-up period. In 22.6% (18/80), a limited wound dehiscence was noted. No other complications were reported nor were there any cases of worsening of the complaints. CONCLUSION/DISCUSSION: In this retrospective cohort study, a significant pain reduction occurred after vestibulectomy in patients who were not responding to conservative treatment. The complication rate of this surgical procedure is low. Vestibulectomy seems to be an effective technique for management of vulvodynia.

Mindfulness and Management of Low Desire and Vulvovaginal Pain.

Mindfulness is defined as present-moment, nonjudgmental awareness. By reducing self-criticism, and depression, and increasing self-compassion, attention, and interoceptive awareness, mindfulness has been found across a variety of systematic reviews and meta-analyses to significantly improve sexual desire, sexual pain, and sex-related distress. It helps individuals connect with their bodies, fostering a deeper understanding of sensations and desires while reducing the focus on negative, judgmental, and catastrophic sex-related and pain-related thoughts. By teaching individuals to focus on bare sensations, mindfulness has also been found to significantly reduce vulvovaginal pain intensity with improvements retained a year later.

Psychosocial Factors Associated With Vulvodynia.

OBJECTIVES: We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life. MATERIALS AND METHODS: PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized. RESULTS: A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis. CONCLUSIONS: The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.

Vestibulodynia: Clinical characteristics, first-line treatments, and factors associated with escalation of treatment with EMG-guided injections of botulinum toxin in a retrospective french cohort study.

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

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.

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.

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.

Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

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.

Efficacy of in-office lysis of clitoral adhesions with excision of keratin pearls on clitoral pain and sexual function: a pre-post interventional study.

BACKGROUND: Keratin pearls are foci of central keratinization within concentric layers of squamous cells that can form under the clitoral prepuce and cause pain (clitorodynia); in-office removal of keratin pearls may reduce clitoral pain and improve sexual function. AIM: This study aims to investigate clitoral pain and sexual function in women with partial clitoral phimosis and keratin pearls before and after in-office lysis of clitoral adhesions with keratin pearl excision (LCA-KPE). METHODS: A pre-post interventional study evaluated patients who underwent LCA-KPE between January 2017 and February 2023 in 2 metropolitan gynecology clinics specializing in vulvar pain. Patients presenting with keratin pearls and partial clitoral phimosis identified through retrospective chart review were asked to complete postprocedure questionnaires and provide subjective responses on clitoral discomfort, sexual function, sexual distress, and their experience with in-office LCA-KPE. Bivariate analyses with paired t tests were conducted to determine the effect of LCA-KPE. Qualitative data were analyzed with thematic coding. OUTCOMES: An 11-point pain visual analog scale was utilized to determine pre- and postprocedure clitoral discomfort and difficulty with orgasm. Female sexual dysfunction was measured with the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised. RESULTS: A total of 32 of 74 patients who met inclusion criteria completed postprocedure surveys (43% response rate). Mean clitoral pain for respondents was 6.91 at baseline and 2.50 after LCA-KPE (P < .001). Mean difficulty with orgasm was significantly decreased from 5.45 at baseline to 3.13 after LCA-KPE (P < .001). Participants had a mean FSFI total score of 17.68 after treatment compared with a mean total baseline FSFI of 12.12 (P = .017). The mean FSFI score for pain was 2.43 at follow-up compared with 1.37 at baseline (P = .049). There was no significant difference in the mean Female Sexual Distress Scale-Revised score before vs after the procedure (P = .27). Qualitative themes described the procedure as painful but worthwhile, with 77% of participants reporting the overall experience as positive. Recurrence rate overall was 28%, with a median of 2 repeat procedures. CLINICAL IMPLICATIONS: Recognizing keratin pearls as a structural cause of clitoral pain and offering in-office treatment is an important tool in addressing clitorodynia and improving sexual function. STRENGTHS AND LIMITATIONS: This is the largest study to date documenting the occurrence, identifying associated pain conditions, and evaluating procedural outcomes for clitoral keratin pearls. This study was limited by a relatively small sample size. CONCLUSION: In-office LCA-KPE significantly reduced clitoral discomfort and difficulty with orgasm.

Relationship Between Childhood Sexual Abuse, Obesity, and Vulvodynia in Adulthood.

OBJECTIVE: The aim of the study is to assess the relationship between childhood sexual abuse, obesity, and vulvodynia among adult women participating in a population-based longitudinal vulvodynia study. MATERIALS AND METHODS: Surveys assessed health status, diagnoses, risk factors, and screening test outcomes for women with vulvodynia. Associations between childhood sexual abuse (CSA) and obesity, CSA and vulvodynia, and obesity and vulvodynia were investigated. A multivariate model was used to determine if obesity mediates and/or modifies the relationship between CSA and vulvodynia. RESULTS: Of 2,277 women participating in the study, 1,647 completed survey data on CSA at 18 months, body mass index at 24 months, and vulvodynia over the first 54 months of the survey. Mean age was 50.9 ± 15.8 years. Overall, race and ethnicity were 77.4% White, 15.7% Black, 2.4% Hispanic, and 4.5% other. Five hundred thirty-nine participants (32.7%) were obese (body mass index >30) and 468 (28.4%) were overweight. Physical CSA before age of 18 years was reported by 20.0% ( n = 329). During the study, 22.0% ( n = 362) screened positive for vulvodynia on one or more surveys. After controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of CSA before age of 18 years ( p = .013 and p < .001, respectively), but obesity was not associated with screening positive for vulvodynia ( p = .865). In addition, multivariate analysis indicated no mediation of the CSA/vulvodynia relationship by obesity. CONCLUSIONS: Although obesity and vulvodynia were independently associated with a history of CSA, obesity did not mediate or modify the relationship between CSA and vulvodynia in adulthood.

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.

"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.

Is Vulvodynia Associated With an Altered Vaginal Microbiota?: A Systematic Review.

INTRODUCTION: Vulvodynia is defined as vulvar pain of at least 3 months' duration, without clear identifiable cause, which may have potential associated factors. It can have a significant impact on women's quality of life due to a combination of physical pain, emotional distress, and limited treatment options. Despite affecting a considerable number of women worldwide, the causes and underlying mechanisms of vulvodynia remain poorly understood. Given the recognized association of the vaginal microbiota with various gynecologic disorders, there has been growing interest in exploring the potential role of the vaginal microbiota in the etiology of vulvodynia. This systematic review aims to evaluate the current literature on the association between the vaginal microbiota and vulvodynia. MATERIAL AND METHODS: A systematic search of multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, was conducted to identify relevant peer-reviewed studies up to May 12, 2023. The following search terms were used across these databases: "vulvodynia," "vestibulodynia," "vulvar vestibulitis," "microbiome," "microbiota," and "flora." RESULTS: A total of 8 case-control studies were included, the quality of which was assessed using the Newcastle-Ottawa Scale. Data extraction and synthesis were performed using a standardized protocol. In most studies, no major differences were found between the vaginal bacterial composition of women with vulvodynia and that of controls. No specific bacterial taxa were consistently associated with vulvodynia. The relationship between vaginal microbiota diversity and vulvodynia remains to be fully understood. CONCLUSIONS: The role of vaginal microbiota in vulvodynia, if any, remains unclear. Because of the cross-sectional nature of the included studies, it is not possible to make any causal inferences. Further research, using larger and more diverse study populations and advanced sequencing techniques, is necessary to gain a better understanding of the potential relationship between the vaginal microbiota and vulvodynia.

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.

Inflammation, lipid dysregulation, and transient receptor potential cation channel subfamily V member 4 signaling perpetuate chronic vulvar pain.

ABSTRACT: Localized provoked vulvodynia is characterized by chronic vulvar pain that disrupts every aspect of the patient's life. Pain is localized to the vulvar vestibule, a specialized ring of tissue immediately surrounding the vaginal opening involved in immune defense. In this article, we show inflammation is the critical first step necessary for the generation of pain signals in the vulva. Inflammatory stimuli alone or combined with the transient receptor potential cation channel subfamily V member 4 (TRPV4) agonist 4α-phorbol 12,13-didecanoate stimulate calcium flux into vulvar fibroblast cells. Activity is blocked by the TRPV4 antagonist HC067047, denoting specificity to TRPV4. Using lipidomics, we found pro-resolving lipids in the vulvar vestibule were dysregulated, characterized by a reduction in pro-resolving mediators and heightened production of inflammatory mediators. We demonstrate specialized pro-resolving mediators represent a potential new therapy for vulvar pain, acting on 2 key parts of the disease mechanism by limiting inflammation and acutely inhibiting TRPV4 signaling.

Efficacy of Physiotherapy for Treating Vulvodynia: A Systematic Review.

OBJECTIVES: We set out to assess the efficacy of physiotherapy for vulvodynia. MATERIALS AND METHODS: PubMed, Embase, Scopus, Web of Science, SciELO, PEDro, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched in February 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Cochrane Risk of Bias tool (Rob 2). Because of the high heterogeneity presented between the studies, it was not possible to carry out qualitative analysis. The results were presented narratively. This systematic review was registered with the PROSPERO database. RESULTS: A total of 2,274 articles were retrieved. Seven studies met the criteria and were included in a systematic review, which included a total of 477 patients. The interventions included were electromyography biofeedback ( n = 2), transcutaneous electrical nerve stimulation ( n = 1), transcranial direct current stimulation ( n = 1), low-intensity shockwave ( n = 1), physiotherapy treatment ( n = 1), and pelvic floor exercise with behavioral modification ( n = 1). All studies evaluated pain reduction, 5 evaluated sexual function, and 2 evaluated quality of life. All interventions were effective for the main outcomes; only the transcranial direct current stimulation intervention showed no significant difference when compared with the placebo or sham group. Three studies presented a high risk of bias due to the lack of blinding. CONCLUSIONS: The studied interventions (electromyography biofeedback, transcutaneous electrical nerve stimulation, shockwave, physiotherapy, and pelvic floor exercise) seem to improve pain, sexual function, and quality of life. However, the heterogeneity of the studies prevented meta-analysis. In addition, well-designed trials are needed to improve the certainty of this evidence.