Platelet-Rich Plasma in Urogynecology: A Case Series.

Platelet-rich plasma (PRP) use in urogynecology is expanding as it shows good results with minimal side effects. We present three new indications of PRP use in urogynecology that have not been previously reported. Our case series demonstrated that PRP improved wound healing and recovery in a woman with chronic obstetric anal sphincter injuries (OASIS) after home delivery, decreased pain in a patient suffering from vulvodynia, and enhanced epithelization in recurrent vaginal stenosis after Fournier gangrene. We have also reviewed patient selection criteria, PRP preparation prerequisites, and techniques. A safe, simple protocol with an optimal platelet yield without using commercial PRP kits is described.

Mathematical Approach to Synergistic Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Series Utilizing Principal Component Analysis, Cluster Analysis, and Combination Laser Therapy.

This case series presents three patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia, demonstrating the efficacy of an individualized treatment approach using cluster analysis and combination laser therapy. Principal component analysis (PCA) was used to visualize the dynamic nature of symptom clusters and guide treatment decisions. Case 1 was a 41-year-old woman initially classified as Cluster 1 (PCA coordinates: 1.65, 0.03) transitioned to Cluster 2 (-16.93, -21.75) after bladder hydrodistension. Subsequent Fotona laser (Ljubljana, Slovenia) treatment resulted in the complete resolution of symptoms. Case 2 was a 55-year-old woman, contraindicated for hormone therapy due to breast cancer history, presented as Cluster 2 (PCA coordinates: -24.16, 8.74). Fotona laser treatment shifted her to Cluster 1 (11.22, -20.22), followed by bladder hydrodistension for complete cure. Case 3 was a 49-year-old woman, initially in Cluster 0 (PCA coordinates: 1.892, 30.11), who underwent fulguration for Hunner's lesions. Posttreatment, she moved to Cluster 2 (-24.31, 1.767) and achieved full recovery after Fotona laser therapy. The dynamic nature of symptom clusters, visualized through PCA, guided treatment decisions. The PCA transformation, represented as y =WTz, where z is the standardized symptom vector and W is the principal component matrix, allows for the objective tracking of symptom changes. Combination Fotona laser therapy, including vaginal erbium YAG and neodymium YAG, has proven effective in managing vulvar pain, particularly when hormone therapy is contraindicated. This approach, addressing both urological and gynecological aspects, resulted in sustained symptom improvement for over 12 months in all cases. This case series highlights the synergistic relationship between BPS/IC and vulvodynia, demonstrating the efficacy of comprehensive, adaptive treatment strategies guided by mathematical analysis for complex pelvic pain syndromes.

The Importance of Psychological Assessment in the Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Report.

This case report emphasizes the crucial role of psychological assessment in the management of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia. A 48-year-old woman with a five-year history of refractory BPS/IC and vulvodynia presented with frequent urination, pelvic pain, and severe dyspareunia, which led to sexual aversion and divorce from her partner. Previous treatments, including lifestyle modifications, analgesics, anticholinergics, hydrodistension, intravesical dimethyl sulfoxide, and psychiatric interventions, had been ineffective. Psychological assessments using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Toronto Alexithymia Scale-20 revealed severe symptoms of depression, anxiety, and alexithymia. Due to the patient's sexual aversion and the absence of a partner, a complete Female Sexual Function Index (FSFI) could not be administered. Instead, a partial FSFI and artificial intelligence-translated reference value of the Female Sexual Distress Scale-Revised were used to assess aspects relevant to the patient's condition. The patient underwent three monthly sessions of Fotona laser therapy, erbium, and neodymium laser at one-month intervals. Treatment outcomes were evaluated using the Numeric Rating Scale-11, Vulvodynia Total, Interstitial Cystitis Symptom Index, and psychological assessment tools. At the six-month follow-up, all physical and psychological symptoms showed significant improvement and complete remission was achieved at 12 months. Despite the overall positive treatment outcomes, the patient's sexual aversion persisted, and accurate measurement was not possible, highlighting the complexity of addressing sexual function in patients with BPS/IC and vulvodynia. This case report underscores the need for a holistic approach to managing these conditions, addressing both the physical and psychological aspects of the disease.

Cytokine profiles and their roles in development of provoked vulvodynia.

Provoked, localized, vulvodynia (PVD) is the main subtype of vulvodynia. Although the etiology of PVD is still a topic of debate, inflammation caused by cytokines responding to a dysregulated microbiome is one of the leading proposed theories. Therefore, the purpose of our study is to further explore the cytokine profiles in the study group with PVD using multiplex immunoassays based on electrochemiluminescence. We compared a panel of 26 distinct cytokines levels in the study group with PVD (n = 23) to the control group (n = 18) and cytokine concentrations were measured using MESO QuickPlex SQ 120 instrument with 5 different multiplex assays. Statistical analysis used the Mann-Whitney U test, two-sided p-values, and a significance level of α = 0.05. Differences in cytokine concentrations are described as negligible, small, medium, or large based on Cliff's δ. Concentrations of three cytokines were significantly lower in the PVD group: a large difference in IP-10 (p = 0.029*) and medium differences in IL-1RA4 (p = 0.030*) and IL-12 (p = 0.034*). One cytokine level was significantly higher in the PVD group: a medium difference for IL-6 (p = 0.037*). Due to the lack of consistency in elevation of inflammatory profiles, it is not enough to support persistent inflammation as the etiology behind PVD. However, these findings may indicate there is a possible immune response deficiency in some patients who have PVD. The resemblance of cytokine profile in our study to cytokine profile of people with chronic yeast infection further support this proposed mechanism behind PVD. Future studies involving history and testing for yeast infection are necessary to explore this possibility further.

Central sensitization symptoms in vulvodynia: exploring the role of temperament, personality traits, childhood adverse events, defense mechanisms, and mental pain on quality of life.

BACKGROUND: Vulvodynia is a chronic pain syndrome characterized by persistent vulvar pain, occurring without clinically identifiable disorders. Central sensitization (CS) is suggested to play a role in the pathophysiology of vulvodynia, as for other nociplastic pain conditions. AIM: This study delves into the complex interplay between psychosocial factors and CS burden in women with vulvodynia, aiming to identify potential predictors (temperament, personality traits, childhood adverse events, defense mechanisms, and mental pain) and understand their impact on quality of life (QoL). METHODS: A cohort-based cross-sectional web survey of 357 women with vulvodynia. OUTCOMES: Outcomes included 8 self-report measures to assess the Central Sensitization Inventory (CSI) and psychological variables, including sensory processing sensitivity, traumatic experiences, personality traits, defense mechanisms, and mental pain. RESULTS: Hierarchical multiple regression analyses were conducted in study 1, revealing that the following predicted higher CSI scores in women with vulvodynia: higher emotional overexcitability, decreased low sensory threshold, increased bodily threat experiences, elevated psychoticism, greater use of immature and neurotic defense mechanisms, and heightened mental pain. The final regression model identified the following as the strongest predictors of CS: low sensory threshold (ß = 0.316), bodily threat experiences (ß = 0.145), neurotic defenses (ß = 0.210), and mental pain (ß = 0.269). In study 2, the model presented interactions among these psychological factors in predicting CSI values explaining 48.9% of the variance in CS, 30.3% in psychological QoL, and 57.1% in physical QoL. CLINICAL TRANSLATION: This model opens discussion for tailored psychological interventions aimed to improve overall QoL in women with vulvodynia. STRENGTHS AND LIMITATIONS: Strengths of the study include innovative insights into the interplay between psychological variables and the construct of CS and quality of life. As a limitation, the research was conducted as a cross-sectional study with self-reported measures. CONCLUSION: The study calls for comprehensive assessments that consider physical and mental aspects, paving the way for holistic health care approaches in the management of vulvodynia.

Evaluation of the Effectiveness of Combined Treatment with Intravaginal Diazepam and Pelvic Floor Rehabilitation in Patients with Vulvodynia by Ultrasound Monitoring of Biometric Parameters of Pelvic Muscles: A Pilot Study.

(1) Background: Vulvodynia is characterized by vulvar pain for at least three months and may have related variables, one of these being pelvic floor hypertonus. The purpose of this study was to compare the therapeutic effectiveness of two weekly sessions of pelvic floor rehabilitation and 5 mg of vaginal diazepam daily vs. pelvic floor rehabilitation alone in individuals with vulvodynia. (2) Methods: A single-center, not-blind, randomized study enrolled 20 vulvodynic patients: A total of 10 were treated with dual therapy (intravaginal diazepam and pelvic floor rehabilitation), and 10 were treated with only pelvic floor rehabilitation. All of them underwent a pelvic floor ultrasound examination and VAS pain and Marinoff scale assessments before the beginning of therapy as well as three and six months later. (3) Results: The elevator plate angle ranged from 8.2 to 9.55 (p = 0.0005), hiatal area diameter ranged from 1.277 to 1.482 (p = 0.0002), levator symphysis distance ranged from 3.88 to 4.098 (p = 0.006), anorectal angle ranged from 121.9 to 125.49 (p = 0.006), Marinoff scale ranged from 2.3 to 1.4 (p = 0.009), and VAS scale ranged from 5.8 to 2.8 (p < 0.001). (4) Conclusions: This pilot study demonstrates that the suggested treatment improves the hypertonicity of the pelvic floor, as measured by ultrasound parameters, correlating with a reduction in symptomatology.

Effectiveness of nonpharmacological conservative therapies for chronic pelvic pain in women: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of nonpharmacological conservative therapies for women with CPP. DATA SOURCES: A systematic search of electronic databases (Amed, CINAHL, PsycINFO, SportDiscuss, Medline, PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed in January 2023, and updated in December 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing a nonpharmacological conservative therapy to inert (eg, placebo, usual care) or nonconservative (eg, surgical, pharmacological) treatment were included. Conservative therapies of interest to this review were: multimodal physical therapy, predominantly psychological approaches, acupuncture, and other tissue-based monotherapies (eg, electrophysical agents, manual stretching). STUDY APPRAISAL AND SYNTHESIS METHODS: All study data were aggregated, and analyses of the included studies were performed. Effects on pain; sexual measures; psychological and physical function; health-related quality of life; symptom severity/bother; pelvic floor muscle function and morphometry; perceived improvement; and adverse events were analyzed. Meta-analyses (random effects model) were conducted using postintervention scores for data that included similar interventions and outcomes. Standardized mean differences were calculated. A narrative summary of findings that could not be included in the meta-analysis is provided. The quality of the evidence was assessed with the Physiotherapy Evidence Database scale and the certainty of evidence with Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: Of 5776 retrieved studies, 38 randomized controlled trials including 2168 women (mean age 35.1±8.6) were included. Meta-analyses revealed that multimodal physical therapy resulted in lower pain intensity compared to inert or nonconservative treatments in both the short (standardized mean difference -1.69, 95% confidence interval -2.54, -0.85; high certainty) and intermediate-terms (standardized mean difference -1.82, 95% confidence interval -3.13, -0.52; moderate certainty), while predominantly psychological approaches resulted in no difference in pain intensity (standardized mean difference -0.18, 95% confidence interval -0.56, 0.20; moderate certainty) and a slight difference in sexual function (standardized mean difference -0.28, 95% confidence interval -0.52, -0.04; moderate certainty). The level of evidence regarding the meta-analysis of the effects of acupuncture on pain intensity (standardized mean difference 1.08, 95% confidence interval -1.38, 3.54, nonstatistically significant results in favor of control treatment) precluded any statement of certainty. A limited number of trials investigated individual tissue-based monotherapies, providing a restricted body of evidence. CONCLUSION: This systematic review with meta-analysis revealed that multimodal physical therapy is effective in women with chronic pelvic pain with a high certainty of evidence.

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.

Investigating the overlapping presentation of irritable bowel syndrome and vulvodynia: a scoping review of the evidence and mechanisms.

INTRODUCTION: Vulvodynia is a complex and multifactorial medical condition characterized by pain in the vulvar area without any identifiable cause. Vulvodynia is underdiagnosed, leading to increased risk of sexual dysfunction and reduced quality of life. Irritable bowel syndrome (IBS) is a gastrointestinal disorder predominantly affecting women. Vulvodynia and IBS frequently co-occur in women, with a 2- to 4-fold increased likelihood of IBS diagnosis in those with vulvodynia. These conditions may share underlying causes, highlighting the need for research to better understand their shared pathophysiology and develop effective therapeutics. OBJECTIVE: The aim of this scoping review was to assess the evidence of simultaneous presentation of IBS and vulvodynia. METHODS: A comprehensive search was conducted in 6 databases between inception of database and August 2023: PubMed, Web of Science, Scopus, Science Direct, Google Scholar, and Cochrane Library. Studies included primary research about IBS and vulvodynia in terms of presentation overlap, diagnosis, or treatment. Data were extracted from eligible studies, summarized, and collated. RESULTS: Of the 306 unique articles identified, 33 were included in the final analysis: 20 cross-sectional studies, 4 case-control studies, 2 case reports, 4 cohort studies, 2 quasi-experimental studies, and 1 randomized trial. Common themes included a high prevalence of overlapping vulvodynia and IBS with a significant diagnostic delay in vulvodynia, mast cell involvement and visceral hypersensitization as common pathophysiology, and the need for a multimodal treatment. CONCLUSION: Our review adds to the evidence that there is an association between vulvodynia and IBS. Despite this, research on the underlying molecular mechanisms of this association is scarce, and diagnostic delays persist for vulvodynia. Increasing awareness of the overlap of these conditions will improve screening for vulvodynia in the patient population with IBS, thereby improving the diagnostic delay, and understanding the pathophysiology will enable treatment strategies that address both conditions.

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.

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.

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.

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.

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.

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.