Symptom-associated alterations in functional connectivity in primary and secondary provoked vestibulodynia.

ABSTRACT: Primary provoked vestibulodynia (PVD) is marked by the onset of symptoms at first provoking vulvar contact, whereas secondary PVD refers to symptom onset after some period of painless vulvar contact. Different pathophysiological processes are believed to be involved in the development and maintenance of primary PVD and secondary PVD. The primary aim of this study was to test the hypotheses that the resting state functional connectivity of the brain and brain stem regions differs between these subtypes. Deep clinical phenotyping and resting state brain imaging were obtained in a large sample of a women with primary PVD (n = 46), those with secondary PVD (n = 68), and healthy control women (n = 94). The general linear model was used to test for differences in region-to-region resting state functional connectivity and psychosocial and symptom assessments. Direct statistical comparisons by onset type indicated that women with secondary PVD have increased dorsal attention-somatomotor network connectivity, whereas women with primary PVD predominantly show increased intrinsic resting state connectivity within the brain stem and the default mode network. Furthermore, compared with women with primary PVD, those with secondary PVD reported greater incidence of early life sexual abuse, greater pain catastrophizing, greater 24-hour symptom unpleasantness, and less sexual satisfaction. The findings suggest that women with secondary PVD show greater evidence for central amplification of sensory signals, whereas women with primary PVD have alterations in brain stem circuitry responsible for the processing and modulation of ascending and descending peripheral signals.

Pelvic Floor Biometric Changes Assessed by 4D Translabial Ultrassound in Women With Vulvodynia Submitted to Physical Therapy: A Pilot Study of a Randomized Controlled Trial.

BACKGROUND: Vulvodynia is a disabling condition in which pelvic floor muscles' (PFM) hypertonicity plays an important role. AIM: To evaluate biometric changes in PFM in women with vulvodynia undergoing kinesiotherapy treatment protocol (KTP). METHODS: A single-blinded randomized controlled trial of 57 women with vulvodynia randomly assigned to either KTP + amitriptyline or amitriptyline alone (controls) for treatment. Four-dimensional translabial ultrasound assessed PFM regarding symphysis-levator distance at rest, anorectal angle at rest, excursion of the levator plate angle, and levator hiatal narrowing. Volunteers underwent a vaginal examination for a cotton swab test (CST), fulfillment of Friedrich criteria score and PFM power of contraction, and completed a diary of sexual pain and frequency of vaginal intercourse. Outcomes were assessed at baseline and after 8 weeks of treatment. OUTCOMES: Primary outcomes were differences in biometric parameters assessed by four-dimensional translabial ultrasound after treatment, between groups. Secondary outcomes were changes in clinical variables (CST, Friedrich criteria, PFM power of contraction, frequency of intercourse, and intensity of sexual pain) between groups and correlation analysis between biometric parameters and clinical variables. RESULTS: Only the KTP group had statistically significant changes in biometric parameters after treatment (symphysis-levator distance: 0.22 ± 0.2, 95% CI = 0.1-0.4, P = .008; levator hiatal narrowing: -0.33 ± 0.2, 95% CI = -1 to -0.2, P = .04). Comparisons between groups showed that symphysis-levator distance (0.3, 95% CI = 0.2-0.6, P = .005) and excursion of levator plate angle (4.9, 95% CI = -0.4 to 10.1, P = .02) improved significantly after KTP treatment. Clinical variables showed greater improvement in the group treated with KTP for CST (difference of -3.7, 95% CI = -7 to -0.4, P = .01), Friedrich criteria (difference of -1.9, 95% CI = -3.2 to -0.6, P = .003), PFM power of contraction (0.3, 95% CI = 0.1-0.6, P = .05) and intensity of sexual pain (reduction of 1.7, 95% CI = -3.1 to -0.2, P = .01). Some clinical and biometric variables correlated positively, for example, frequency of vaginal intercourse and anorectal angle (P = .04; r = 0.25), or inversely, for example, pain intensity at CST and anorectal angle (P = .004, r = -0.31). CLINICAL IMPLICATIONS: This study provides evidence on efficiency of a physical therapy protocol for improvement of symptoms of vulvodynia and hypertonicity changes. CONCLUSION: This pilot study suggests that KTP for women with vulvodynia promoted significant changes in PFM biometric measures, consistent with alterations in hypertonicity and clinical improvement. Bardin MG, Giraldo PC, Martinho N. Pelvic Floor Biometric Changes Assessed by 4D Translabial Ultrassound in Women With Vulvodynia Submitted to Physical Therapy: A Pilot Study of a Randomized Controlled Trial. J Sex Med 2020;17:2236-2246.

Altered gray matter volume in sensorimotor and thalamic regions associated with pain in localized provoked vulvodynia: a voxel-based morphometry study.

Multimodal neuroimaging studies provide support for a role of alterations in sensory processing circuits and endogenous pain modulatory systems in provoked vestibulodynia (PVD). In this study, we tested the hypotheses that PVD compared with healthy controls (HCs) would demonstrate gray matter volume (GMV) alterations in regions associated with sensorimotor, corticothalamic, and basal ganglia circuits. We also tested the replicability of previously reported gray matter increases in basal ganglia and hippocampal volumes in PVD vs HCs. In addition, disease specificity of GMV alterations were examined by comparing PVD with another chronic pain disorder. Finally, we examine whether GMV alterations are correlated with symptom measures. Structural magnetic resonance imaging was obtained in 119 premenopausal women (45 PVD, 45 HCs, and 29 irritable bowel syndrome [IBS]). A voxel-based morphometry analysis was applied to determine group differences in the hypothesized regions of interest. Compared with HCs, PVD women exhibited greater GMV in the basal ganglia, hippocampus, and sensorimotor cortices. Compared to patients with IBS, women with PVD had greater GMV in the hippocampus, and sensorimotor network, but lower GMV in the thalamus and precentral gyrus. Regional GMV alterations were associated with patient reports of pain during intercourse and muscle tenderness. The current findings provide further evidence that GMV is increased in PVD compared with HCs in several regions of the sensorimotor network and the hippocampus in patients with PVD. In addition, GMV distinct alterations in the sensorimotor network were identified between 2 pelvic pain disorders, PVD compared with IBS.

Reliability of vulvar blood perfusion in women with provoked vestibulodynia using laser Doppler perfusion imaging and laser speckle imaging.

BACKGROUND: Microvascular assessment has become increasingly used in gynecology to better understand the pathophysiology of various vulvar conditions and to study sexual function. Alteration in blood perfusion of the vulvar area has been observed using laser technologies in women with provoked vestibulodynia (PVD), the leading cause of vulvar pain. However, no studies have thus far investigated the reliability of and agreement between lasers for evaluating vulvar blood perfusion. OBJECTIVES: The main objective was to investigate the between-session reliability of the laser Doppler perfusion imaging (LDPI) and laser speckle contrast imaging (LSCI) for assessing blood perfusion of the vulvar vestibule in women with PVD. Secondary aims were to evaluate the association and agreement between the two laser technologies. METHODS: Twenty-six women with PVD participated in the study. Blood perfusion of the vulvar vestibule was assessed with LDPI and LSCI during two sessions 2 to 4 weeks apart. Blood perfusion was analyzed in five specific areas of the vulvar vestibule: 1) 3 o'clock site, 2) 6 o'clock site, 3) 9 o'clock site, 4) central area (delimited by areas 1, 2 and 3), and 5) posterior fourchette. The reliability of the measurements of the two instruments was calculated with intraclass correlation coefficients (ICCs), standard errors of measurement (SEMs) and coefficients of variation (CVs). Paired t-tests were also computed to compare the CVs of each laser technology. The association and agreement between LDPI and LSCI measurements were evaluated by Pearson's correlation coefficients and Bland-Altman plots, respectively. RESULTS: Excellent reliability was found for LDPI (ICCs = 0.78-0.80, p < 0.001, SEMs = 16.1-47.9) and LSCI measurements (ICCs = 0.75-0.81, p ≤ 0.001, SEMs = 17.0-52.2) for all vulvar vestibule areas. However, CVs were significantly higher using LDPI (CVs = 15.1-19.8) when compared to LSCI (CVs = 7.0-11.6) for all areas (p ≤ 0.031), except for area 4 (p = 0.079). Significant correlations were found between LDPI and LSCI for all areas (r = 0.58-0.89, p ≤ 0.003). Bland-Altman plots revealed a systematic difference between LDPI and LSCI measurements. CONCLUSION: Findings show that both LDPI and LSCI measurements are reliable for assessing blood perfusion of the vulvar vestibule in women with PVD. The LSCI appears to be a more reliable measurement as it presents less variation than LDPI. Finally, although LDPI and LSCI measurements are related, the systematic difference observed between them makes it impossible to compare absolute units.

Can maximal voluntary pelvic floor muscle contraction reduce vaginal resting pressure and resting EMG activity?

INTRODUCTION AND HYPOTHESIS: The purpose of the present study was to assess whether attempts at a maximal voluntary pelvic floor muscle (PFM) contraction can reduce vaginal resting pressure (VRP) and surface EMG activity in women with and without provoked vestibulodynia (PVD). METHOD: An assessor blinded comparison study included 35 women with and 35 women without PVD. VRP and PFM strength were measured with a high precision pressure transducer connected to a vaginal balloon (Camtech AS, Sandvika Norway). PFM activity was measured before and after three MVCs with surface EMG (NeuroTrac ETS™; Verity Medical, Romsey, UK). Paired sample t test was used to analyze differences within groups and independent sample t test to analyze differences between groups. p value was set at <0.05. RESULTS: Mean age of the participants was 24.3 years (SD 4.7) and mean BMI was 22.0 kg/m2 (SD 2.6). There were no significant differences between the groups in any background variables. PFM contraction led to a statistically significant reduction of VRP in both the PVD (p = 0.001) and the control group (p = 0.027). Surface EMG activity was significantly reduced in the PVD group only (p = 0.001). DISCUSSION: Young, nulliparous women with PVD had significantly lower vaginal resting pressure and sEMG activity after three maximum contractions of the PFM. The results indicate that attempts at voluntary maximal contractions may be investigated as a method of reducing PFM hypertonicity.

Relationships Between 3-Dimensional Transperineal Ultrasound Imaging and Digital Intravaginal Palpation Assessments of the Pelvic Floor Muscles in Women With and Without Provoked Vestibulodynia.

BACKGROUND: Digital intravaginal palpation remains the favored method for clinical assessment of pelvic floor muscle (PFM) function in women; however, there is growing interest in using transperineal ultrasound imaging (TPUSI). TPUSI does not involve vaginal penetration, making it particularly relevant for PFM assessment in women with genito-pelvic pain and penetration disorders. AIMS: To study the relations between measures of PFM morphology and function assessed using 3-dimensional (3D) TPUSI and PFM assessment through intravaginal palpation. METHODS: 77 nulliparous premenopausal women with (n = 38) and without (n = 39) PVD participated. 3D TPUSI was used to measure levator hiatal dimensions at rest, at maximal voluntary contraction (MVC) of the PFMs, and at maximal Valsalva maneuver (MVM). Intravaginal palpation was used to assess PFM strength, PFM tone, PFM relaxation after contraction, and vaginal flexibility; each was scored using an ordinal grading scale. Ultrasound and palpation outcomes were compared using Spearman correlation coefficients and Kruskal-Wallis 1-way analyses of variance by rank. OUTCOMES: Outcomes included ultrasound measures of the levator hiatal area, anteroposterior diameter, and left-right transverse diameter at rest, at MVC, and at MVM; raw and relative changes in hiatal dimensions between rest and MVC and between rest and MVM; and palpation measures of PFM strength, tone, and relaxation after contraction, and vaginal flexibility. RESULTS: Weak to fair correlations were found between ultrasound and palpation measures. A smaller levator hiatus at rest was associated with greater PFM tone, less PFM relaxation, and less vaginal flexibility. Greater levator hiatal constriction and shortening of the hiatal anteroposterior diameter at MVC were associated with greater palpated PFM strength. Greater hiatal distention at MVM was associated with lower PFM tone and greater relaxation. CLINICAL TRANSLATION: 3D TPUSI and intravaginal palpation provide related but distinct information about PFM function in young women with and without PVD with high functioning PFMs. STRENGTHS AND LIMITATIONS: This was the first study to compare PFM assessment using 3D TPUSI and intravaginal palpation in nulliparous premenopausal women. A main strength of the study was the inclusion of women with PVD and asymptomatic controls, which provided a wide range in outcomes because differences in PFM morphology and function exist between women with and without PVD. The lack of inclusion of older women and women with weaker and/or hypotonic PFMs limits the generalizability of the findings. CONCLUSION: Although TPUSI has several advantages, including painless application, it is not recommended as a replacement for digital palpation in the clinical assessment of PFM function. Thibault-Gagnon S, Goldfinger C, Pukall C, et al. Relationships Between 3-Dimensional Transperineal Ultrasound Imaging and Digital Intravaginal Palpation Assessments of the Pelvic Floor Muscles in Women With and Without Provoked Vestibulodynia. J Sex Med 2018;15:346-360.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE: Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system.

Differences in the Biometry of the Levator Hiatus at Rest, During Contraction, and During Valsalva Maneuver Between Women With and Without Provoked Vestibulodynia Assessed by Transperineal Ultrasound Imaging.

INTRODUCTION: Pelvic floor muscle (PFM) involvement is suspected in the pathophysiology of provoked vestibulodynia (PVD); however, the underlying mechanisms are unclear. PFM morphology can be inferred from the biometry of the levator hiatus determined through dynamic ultrasound imaging. AIMS: The aim of this study was to determine the nature of PFM involvement in women with PVD via an evaluation of the biometry of the levator hiatus at rest, upon maximal voluntary contraction (MVC) of the PFMs, and upon maximal Valsalva maneuver (MVM). METHODS: Thirty-eight women with PVD and 39 asymptomatic controls were imaged using 3D transperineal ultrasound. Levator hiatal dimensions (area; left-right [LR] and anteroposterior [AP] diameters) were measured at rest, on MVC, and on MVM. Differences in hiatal dimensions and in relative changes in dimensions from rest to MVC and from rest to MVM were compared between groups using separate 1-way analyses of variance for each measure and task. Analysis of covariance models were used to investigate the impact of levator hiatal dimensions at rest on the relative changes in the levator hiatal dimensions during MVC and MVM. MAIN OUTCOME MEASURES: Levator hiatal area, LR, and AP diameters, at rest, on MVC, and on MVM were the main outcome measures. Relative changes in hiatal dimensions were assessed as the percent change in hiatal area, LR diameter, and AP diameter. RESULTS: In comparison with controls, women with PVD had smaller hiatal areas at rest, on MVC, and on MVM, concurrent with smaller LR diameters on MVM. Women with PVD had a significantly smaller change in hiatal area on MVM than controls, but no differences were evident on MVC. In both groups, smaller levator hiatal dimensions at rest were associated with smaller relative decreases in dimensions on MVC and larger relative increases in dimensions on MVM. CONCLUSION: In comparison to controls, women with PVD appear to have narrower levator hiatus' and less capacity to distend their hiatus on Valsalva. The state of the PFMs at rest appears to significantly influence biometric changes in the PFMs during contraction and Valsalva.

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.

Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and nonpainful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.

Morphometry of the pelvic floor muscles in women with and without provoked vestibulodynia using 4D ultrasound.

INTRODUCTION: It has been suggested that pelvic floor muscles (PFMs) play an important role in provoked vestibulodynia (PVD) pathophysiology. Controversy in determining their exact contribution may be explained by methodological limitations related to the PFM assessment tools, specifically the pain elicited by the measurement itself, which may trigger a PFM reaction and introduce a strong bias. AIM: The aim of this study was to compare PFM morphometry in women suffering from PVD to asymptomatic healthy control women using a pain-free methodology, transperineal four-dimensional (4D) ultrasound. METHODS: Fifty-one asymptomatic women and 49 women suffering from PVD were recruited. Diagnosis of PVD was confirmed by a gynecologist following a standardized examination. All the participants were nulliparous and had no other urogynecological conditions. The women were evaluated in a supine position at rest and during PFM maximal contraction. MAIN OUTCOME MEASURES: Transperineal 4D ultrasound, which consists of a probe applied on the surface of the perineum without any vaginal insertion, was used to assess PFM morphometry. Different parameters were assessed in sagittal and axial planes: anorectal angle, levator plate angle, displacement of the bladder neck, and levator hiatus area. The investigator analyzing the data was blinded to the clinical data. RESULTS: Women with PVD showed a significantly smaller levator hiatus area, a smaller anorectal angle, and a larger levator plate angle at rest compared with asymptomatic women, suggesting an increase in PFM tone. During PFM maximal contraction, smaller changes in levator hiatus area narrowing, displacement of the bladder neck, and changes of the anorectal and of the levator plate angles were found in women with PVD compared with controls, which may indicate poorer PFM strength and control. CONCLUSION: Using a reliable and pain-free methodology, this research provides sound evidence that women with PVD display differences in PFM morphometry suggesting increased tone and reduced strength.