Central sensitization inventory in endometriosis.

ABSTRACT: A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.

Symmetry in Paraspinal Muscles as a Predictor of the Development of Pregnancy-Related Low Back and Pelvic Pain: A Prospective Study.

OBJECTIVE: To determine the asymmetry in the paraspinal muscle before pregnancy and evaluate its association with pregnancy-associated lumbopelvic pain (LPP). METHODS: This was a prospective case-control study conducted from January 2017 and December 2018. A total of 171 subjects (mean age ± SD, 27.4 ± 5.8 years) were finally divided into the LBP group, PGP group, and no LPP group. Each subject was asked to follow a standardized clinical imaging protocol before the pregnancy. The area of muscles (multifidus, erector spinae, and psoas muscles) on the axial slice at mid-disc of L4 -L5 and L5 -S1 were segmented and then the cross-sectional area (CSA) of a particular muscle was measured by outlining the innermost fascial border surrounding each muscle. The mean value of F-CSA's ratio to T-CSA (F/T CSA) was used to determine whether the bilateral paraspinal muscle was asymmetrical. Total muscle CSA (T-CSA) represents the sum of CSA of interested three muscles. The signal intensity can distinguish fat and muscle tissue in a different range. Based on this, functional CSA (F-CSA), represented by fat-free area, was evaluated quantitively by excluding the signal of the deposits of intramuscular fat. Total muscle CSA (T-CSA), functional CSA (F-CSA), and the ratio of F-CSA to T-CSA (F/T CSA) were measured unilaterally and compared between groups. Logistic regression was performed to determine the risk factors for pregnancy-associated LPP. The Pearson correlation coefficient was performed to test the relationship between asymmetry in F/T-CSA and pain rating. RESULTS: A total of 124 subjects (72.5%) (28.5 ± 5.2 years) had LPP during pregnancy. Forty-eight (38.7%) individuals had low back pain (LBP) and 76 (61.3%) had pelvic girdle pain (PGP). Seventy-six women (44.4%) were determined to have asymmetry in paraspinal muscle according to the definition in this methods section. The duration of follow-up was 24 months postpartum. A total of 39 (31.5%) women unrecovered from LPP. F/T-CSA was significantly decreased for LBP in the PGP group than in the and control group (0.03 ± 0.02 vs 0.05 ± 0.03 vs 0.12 ± 0.05, P < 0.001). Meanwhile, significant differences were detected in both groups (all P < 0.001). In patients with LBP, the level of paraspinal asymmetry, represented by the difference in F/T-CSA, was positively correlated with pain scores (r = 0.52, P < 0.01). However, no statistically significant correlation between pain scores and paraspinal asymmetry was found in PGP (r = 0.42, P > 0.05). Asymmetry in the paraspinal muscle (adjusted OR = 1.5), LBP (adjusted OR = 1.6), LPP in a previous pregnancy (adjusted OR = 1.4), sick leave ≥90 days (adjusted OR = 1.2), and heavy labor (adjusted OR = 1.2) were risk factors for the unrecovered LPP during pregnancy. CONCLUSIONS: Asymmetrical muscular compositions could lead to abnormal biomechanics for the segmental motions. Lateral-directed physical training and stretching may help decrease the occurrence and severity of this condition.

Cross-organ sensitization between the prostate and bladder in an experimental rat model of lipopolysaccharide (LPS)-induced chronic pelvic pain syndrome.

BACKGROUND: The aim of the current study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function via prostate-to-bladder cross-sensitization in a rat model of lipopolysaccharide (LPS)-induced prostate inflammation. METHODS: Male rats were intraprostatically injected with LPS or saline, serving as control. Micturition parameters were examined in a metabolic cage 10 or 14 days later. Subsequently, to evaluate bladder function, cystometry was performed. Micturition cycles were induced by saline infusion and cholinergic and purinergic contractile responses were measured by intravenous injection with methacholine and ATP, respectively. Thereafter, the prostate and bladder were excised and assessed histopathologically for possible inflammatory changes. RESULTS: Metabolic cage experiments showed increased urinary frequency in rats with LPS-induced CP/CPPS. Cystometry showed a significant increase in the number of non-voiding contractions, longer voiding time and lower compliance in CP/CPPS animals compared to controls. Induction of CP/CPPS led to significantly reduced cholinergic and purinergic bladder contractile responses. Histopathological analysis demonstrated prostatic inflammation in CP/CPPS animals. There were no significant differences between the groups regarding the extent or the grade of bladder inflammation. Prostate weight was not significantly different between the groups. CONCLUSIONS: The present study shows that prostate-to-bladder cross-sensitization can be triggered by an infectious focus in the prostate, giving rise to bladder overactivity and alterations in both afferent and efferent signalling. Future studies are required to fully understand the underlying mechanisms.

Acyloxyacyl hydrolase is a host determinant of gut microbiome-mediated pelvic pain.

Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often with comorbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in patients with IC/BPS. We identified the locus encoding acyloxyacyl hydrolase, Aoah, as a modulator of pelvic pain severity in a murine IC/BPS model. AOAH-deficient mice spontaneously develop rodent correlates of pelvic pain, increased responses to induced pelvic pain models, voiding dysfunction, and anxious/depressive behaviors. Here, we report that AOAH-deficient mice exhibit dysbiosis of gastrointestinal (GI) microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and a "leaky gut" phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Cohousing AOAH-deficient mice with wild-type mice resulted in converged microbiota and altered predicted metagenomes. Cohousing also abrogated the pelvic pain phenotype of AOAH-deficient mice, which was corroborated by oral gavage of AOAH-deficient mice with stool slurry of wild-type mice. Converged microbiota also alleviated comorbid anxiety-like behavior in AOAH-deficient mice. Oral gavage of AOAH-deficient mice with anaerobes cultured from IC/BPS stool resulted in exacerbation of pelvic allodynia. Together, these data indicate that AOAH is a host determinant of normal gut microbiota, and dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS.

Non-venous Pelvic Pain and Roles for Pelvic Floor PT or Pudendal Nerve Blocks.

Non-venous pelvic pain is a dilemma that can frustrate even the most patient of providers. Managing these conditions can be even more bewildering as they require a multidisciplinary approach in most cases. Diet and lifestyle modifications in addition to physical therapy, biofeedback, medications, surgery and integrative medicine modalities can be used alone or in combination to relieve symptoms and should be individualized after proper evaluation and diagnosis. Because most of these conditions are located in the area of pudendal nerve distribution, pudendal nerve blocks have been very successful in helping to control the pain symptoms and should be used judiciously. Here we discuss the common conditions and how physical therapy and pudendal nerve blocks play a significant role in treatment.

Clinical investigation of fertility after uterine artery embolization.

BACKGROUND: Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE: This study aimed to study the clinical, anatomic, and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DESIGN: This was a retrospective cohort study of 398 female patients under the age of 43 years who were treated by uterine artery embolization between 2003 and 2017 for symptomatic fibroids and/or adenomyosis. Uterine artery embolization was performed according to a standardized procedure (fertility-sparing uterine artery embolization technique), with ovarian protection in the event of dangerous utero-ovarian anastomosis. Magnetic resonance imaging and pelvic ultrasounds were performed before and after uterine artery embolization. RESULTS: The overall clinical success rate (ie, resolution of preembolization symptoms such as heavy menstrual bleeding, iron-deficiency anemia, pelvic pressure) was 91.2%, and there were no major complications. One year after uterine artery embolization, we observed a mean 73% reduction in myoma volume. A total of 108 patients (49.3%) presented with dangerous utero-ovarian anastomosis and 33 (14.5%) benefited from ovarian protection. In our group, there were 148 pregnancies and 109 live births; 74 children were born at term; 23 were born preterm, on average at 35.12±2.78 weeks. Including preterm births, the mean birthweight and birth length of the children were within normal limits. Restoration of uterine anatomy and ovarian protection were identified as the main predictive factors for obstetrical success. Restoration was also a major predictive factor for clinical success and was associated with a lower rate of miscarriage. CONCLUSION: This study provided detailed clinical and obstetrical outcomes for 398 female patients who underwent uterine artery embolization for fibroid treatment; it contributes to the identification of anatomic and technical factors that could have an impact on fertility after uterine artery embolization. Further controlled clinical trials are needed to confirm our findings and reevaluate this procedure's indications and limitations for women with a desire to procreate.

Endometriosis: Etiology, pathobiology, and therapeutic prospects.

Endometriosis is a common condition associated with infertility that causes chronic pain in many, but not all, women. It is defined by the presence of endometrial-like tissue outside the uterus. Although the cause and natural history of the disorder remain uncertain, hormonal, neurological, and immunological factors are all implicated in the mechanisms contributing to development of symptoms. Because definitive diagnosis requires surgery, there is often a long diagnostic delay after onset of symptoms. Current interventions for endometriosis have limited efficacy and unacceptable side effects/risks and are associated with high rates of symptom recurrence. Here, we review recent advances in our understanding of the etiology of endometriosis, discuss current diagnostic and treatment strategies, highlight current clinical trials, and consider how recent results offer new avenues for the identification of endometriosis biomarkers and the development of effective non-surgical therapies that are fertility-sparing.

Physiotherapeutic assessment and management of chronic pelvic pain syndrome: A case report.

INTRODUCTION: Chronic pelvic pain syndrome is difficult for the diagnosis and therapy and that means the patient attending the physician or physiotherapist may present various symptoms. There are no guidelines concern physiotherapy diagnosis and treatment of chronic pelvic pain syndrome. This study presents the physiotherapeutic assessment and management in men with pelvic pain symptoms. PATIENT CONCERNS: Forty-six-year-old man attended the physiotherapy consulting room due to symptoms of pain in the perineum, lower abdomen, urethra, and scrotum for a year. Earlier, the patient had consulted a urologist who made a diagnosis of cystitis and prescribed medications that did not get results. DIAGNOSIS: Ultrasound imaging and manual inspection (per rectum) of the pelvic floor was conducted by physiotherapist. Also, the abdominal and lower extremities muscles were assessed. Patient reported pain symptoms during examination of the musculus ischiocavernosus, puboanalis, pubococcygeus, iliococcygeus, coccygeus, and canalis pudentalis seu Alcocki. INTERVENTIONS: The patient was given physiotherapeutic interventions consisting in the manual therapy of the lumbopelvic hip complex and the manual therapy per rectum. OUTCOMES: During 10th session of the physiotherapeutic treatment, patient reported improvement in pain symptoms. A month later, patient reported total alleviation of the pain symptoms during control visit. CONCLUSION: Therapy of chronic pelvic pain syndrome is a process that involves application of different therapies and different approaches. Functional and structural assessment and also therapy conducted by physiotherapist is becoming an integral part of urology and represents 1 possible conservative treatment form.

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Is primary dysmenorrhea a precursor of future endometriosis development?

Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

Prostate-to-bladder cross-sensitization in a model of zymosan-induced chronic pelvic pain syndrome in rats.

BACKGROUND: The aim of the present study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function and pathophysiology. METHODS: To create a model for CPPS, rats were intraprostatically injected with zymosan or saline, serving as control. Metabolic cage experiments were performed 7, 14, or 21 days after zymosan injection and after 14 days in the control group. Thereafter, cystometry was performed in which simulated micturition cycles were induced by saline infusion and contractile responses to the cholinergic agonist methacholine and the purinergic agonist ATP were measured. Following cystometry, the prostate and urinary bladder were excised and assessed histopathologically for possible inflammatory changes. RESULTS: Metabolic cage data revealed a significantly increased urinary frequency in zymosan treated rats. Likewise, the volume per micturition was significantly lower in all CPPS groups compared to controls. Cystometry showed a significant increase in the number of nonvoiding contractions, longer voiding time, and a trend towards lower compliance in CPPS rats compared to controls. Induction of CPPS led to significantly reduced cholinergic and purinergic contractile responses. Histopathological analysis demonstrated prostatic inflammation in all CPPS groups, in particular in later stage groups. Both the extent and grade of bladder inflammation were significantly higher in CPPS groups compared to controls. CONCLUSIONS: The current findings demonstrate a potential prostate-to-bladder cross-sensitization leading to symptoms of bladder overactivity and signs of bladder inflammation. Future clinical studies are required to verify the outcomes of the current study and enable advancement of patient care.

Comparative analysis of the efficacy and safety of endovascular and endoscopic interventions on the gonadal veins in the treatment of pelvic congestion syndrome.

OBJECTIVE: Comparison of the efficacy and safety of endovascular and endoscopic interventions on the gonadal vein in the treatment of patients with pelvic congestion syndrome (PCS). METHODS: We evaluated the treatment outcomes in 95 patients with PCS who underwent endovascular embolization of gonadal veins (EEGV) (group 1, n = 67) or endoscopic resection of the gonadal veins (ERGV) (group 2; n = 28). A comparative analysis of the efficacy and safety of EEGV and ERGV in the treatment of PCS included assessments of their effects on pelvic venous pain, pelvic venous reflux, diameter of the pelvic veins, and restoration of daily activity, as well as treatment safety assessment. Clinical examinations and ultrasound studies of the pelvic veins were repeated at 1, 10, and 30 days, and 36 months after EEGV and ERGV. Pain was assessed using a visual analogue scale and the Von Korff questionnaire. RESULTS: A decrease in pelvic venous pain intensity was observed at 3.6 ± 1.4 days after EEGV and 2.5 ± 0.8 days after ERGV (P = .49 between the groups). At 1 month after the intervention, a complete relief of pelvic pain was reported by 52 and 25 patients in the EEGV and ERGV groups, respectively. The rates of valvular incompetence of the uterine veins were decreased from 85% in both groups at baseline to 3% in group 1 and 0% in group 2 at 36 months after the intervention, respectively. In the early postprocedural period, pain in the femoral or jugular vein puncture site was reported by eight patients (12%) who underwent EEGV (2.2 ± 0.7 scores). Postembolization syndrome was diagnosed in 13 patients (19.4%). After ERGV, all patients experienced pain in the area of the surgical wound, with a severity of 3.9 ± 0.5 scores. Hematoma at the puncture site of the main vein was observed in 6% of patients after EEGV. Protrusion of coils was identified in three patients (4.5%). The VTE incidence was four times greater in group 1 vs group 2 (14 vs 3 patients; P < .05). The relative risk of this complication after EEGV was 1.4 (95% confidence interval, 1.146-1.732). In two patients (7.1%) after the bilateral laparoscopic resection of the gonadal veins, an ileus developed. No complications of anesthesia were observed in either group. CONCLUSIONS: Endovascular and endoscopic techniques for decreasing blood flow through the gonadal veins are effective and safe in treating the PCS. The obvious advantages of EEGV are minimal injury and possibility to perform procedure under local anesthesia. The ERGV is associated with at least similar and, in some cases, even superior outcomes, in the terms of significantly (P < .05) shorter time to the postprocedural pain relief and avoiding postembolization syndrome.

Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study.

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we describe and test a more ecologically-valid paradigm to study the brain response to bladder filling by (1) filling the bladder naturally with oral water ingestion, (2) examining resting state fMRI (rs-fMRI) which is more natural since it is not linked with a specific stimulus, and (3) relating rs-fMRI measures to self-report (urinary urge) and physiologic measures (voided volume). To establish appropriate controls and analyses for future clinical studies, here we analyze data collected from healthy individuals (N = 62) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Participants orally ingested approximately 350 mL of water, and had a 10 min "fuller bladder" rs-fMRI scan approximately 1 h later. A second 10 min "empty bladder" rs-fMRI scan was conducted immediately following micturition. We examined multiple spatial scales of brain function, including local activity, circuits, and networks. We found changes in brain function distributed across micturition loci (e.g., subregions of the salience, sensorimotor, and default networks) that were significantly related to the stimulus (volume) and response (urinary urge). Based on our results, this paradigm can be applied in the future to study the neurobiological underpinnings of urologic conditions.

Bladder sensation evaluation of a carrageenan-induced chronic prostatitis model using a direct measurement of the bladder mechanosensitive single-unit afferent nerve activity.

AIMS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) causes long-standing pain and/or storage symptoms. This study aimed to evaluate the likelihood of deterioration of bladder sensation in a carrageenan-induced CP/CPPS model by direct measurement of the bladder mechanosensitive single-unit afferent nerve activity. METHODS: In this study, male adult Sprague-Dawley rats were used. They were injected 50 µL of 3% λ-carrageenan or its vehicle (saline) into both lobes of the ventral prostate. Seven days following injection, the pain behavior at the pelvic-perineal area (using von Frey filaments), prostatic blood flow (using a laser blood flowmeter), and histology were examined along with cystometry (under conscious free-moving condition) and mechanosensitive single-unit afferent nerve activity (under urethane anesthesia). RESULTS: The prostate showed increased tissue weight and decreased blood flow and inflammatory cell infiltration in the carrageenan group compared to the control group. Consequently, the threshold of the pain behavior was decreased, and the basal and threshold pressures of the bladder were increased in the carrageenan group. In contrast, no significant differences of bladder histology and other cystometric parameters were found between the groups. Regarding Aδ- or C-fibers, the mechanosensitive afferent nerve activities revealed no differences in either group. CONCLUSIONS: The carrageenan-induced CP/CPPS rat model showed edema, ischemia, and inflammatory pain in the prostate, whereas a little change was detected in bladder sensation. These findings, which were evaluated using a direct measurement of the mechanosensitive single-unit afferent nerve activity, suggest that the bladder sensation is unlikely deteriorated in this model.

High-Density Surface Electromyography Assessment of Pelvic Floor Dysfunction in Women with Interstitial Cystitis/Bladder Pain Syndrome.

PURPOSE: Up to 85% of women with interstitial cystitis/bladder pain syndrome have pelvic floor dysfunction and hypertonicity. Current evaluation methodologies lack objective measures of pelvic floor muscle activity. We examined the ability of using intravaginal high-density surface electromyography to quantitatively, objectively and noninvasively map pelvic floor muscle activity and innervation zone locations in patients with interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: Fifteen women with interstitial cystitis/bladder pain syndrome and 15 controls underwent 2 sessions of digital pelvic examinations and high-density surface electromyography assessments. The root mean squared amplitude of high-density surface electromyography was first calculated, and the resting root mean squared ratio was then calculated by normalizing the resting electromyography root mean squared to the peak electromyography amplitude reached during maximum voluntary contraction. Innervation zone distributions were obtained from decomposed high-density surface electromyography signals. The correlation between the root mean squared ratio and interstitial cystitis/bladder pain syndrome symptom scores and pelvic floor muscle alignment were investigated in patients with interstitial cystitis/bladder pain syndrome and healthy controls. RESULTS: Women with interstitial cystitis/bladder pain syndrome demonstrated significantly increased resting root mean squared ratios compared to controls (0.155±0.048 vs 0.099±0.041, p=0.0019). Significant correlations were found between resting root mean squared ratio and patient reported pain (rs=0.523, p=0.003), interstitial cystitis symptom (rs=0.521, p=0.003) and problem indices (rs=0.60, p <0.001). In addition, women with interstitial cystitis/bladder pain syndrome were more likely to have shortened pelvic floor muscles (80%, 12 vs 13.3%, 2, p <0.01). Women with shortened pelvic floor muscles demonstrated significantly higher resting root mean squared ratio compared to those with normal pelvic floor muscle length (0.155±0.046 vs 0.107±0.040, p=0.0058). CONCLUSIONS: Intravaginal high-density surface electromyography offers an objective and quantitative strategy to noninvasively assess pelvic floor muscle dysfunction in women with interstitial cystitis/bladder pain syndrome. Abundant spatiotemporal muscle activity information captured by high-density surface electromyography allows for mapping innervation zone distributions for major pelvic floor muscles.

Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

AIMS: Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress-induced bladder hyperalgesia, a core feature of IC/BPS. METHODS: Wistar-Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14 C]-iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in three dimensional reconstructed brains with statistical parametric mapping. RESULTS: WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress-related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. CONCLUSIONS: CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress-related bladder dysfunction may be a novel approach to the treatment of IC/BPS.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

AIMS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. METHODS: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. RESULTS: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. CONCLUSIONS: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

Description and classification of postpartum chronic pain: A multicentric prospective study.

INTRODUCTION: To classify persistent perineal and pelvic postpartum pain using the classification usually employed in chronic pelvic pain. MATERIAL AND METHOD: Prospective observational study including all women who have consulted an algologist or gynecologist at one of the six French centers for a chronic pain (superior or equal to 3 months) spontaneous linked by the mother with her childbirth were included. During semi-directed interviews, a questionnaire regarding sociodemographic factors and detailed questions about pain were collected. Then, pelvic and perineal pain were classified into 7 pain syndromes: pelvic sensitization (Convergences PP criteria), complex regional pain syndrome (Budapest criteria), pudendal or cluneal neuralgia (Nantes criteria), neuroma, thoraco-lumbar junction syndrome, myofascial pain (muscle trigger zone), fibromyalgia (American College of Rheumatology criteria). The principal objective of this study is to assess the prevalence of each painful disorder. The secondary aims were the description of socio-demographic factors and clinical characteristics of this population, identify the related symptoms and the impact on daily function associated with the chronic pelvic or perineal postpartum pain. RESULTS: 40 women with chronic pelvic or perineal pain spontaneously linked with childbirth were included. 78 % experienced pain for more than 12 months. A large majority had a vaginal birth (95 %) with perineal suture (90 %) and severe acute pain within the first week postpartum (62 %). Postpartum pain impacted participant's sexual activity (80 %), micturition (28 %) and defecation (38 %). In the sample, 17 cases of neuroma, 6 patients with pudendal or cluneal neuralgia, 13 patients with pelvic sensitization and 2 cases of fibromyalgia were identified. Complex regional pain syndrome was diagnosed in 8 patients, and myofascial pain in 11 women, and only 1 patient had thoraco-lumbar junction syndrome. Neuropathic pain was found in 31 participants (77.5 %) according to DN4 criteria. DISCUSSION: The classification scheme proposed in this study may be a very useful tool to investigate postpartum pelvic and perineal pain and to propose a treatment.

Unique Case of Recurrent Pelvic Congestion Syndrome Treated with Median Sacral Vein Embolization.

BACKGROUND: Pelvic congestion syndrome (PCS) is defined as noncyclical pelvic pain or discomfort caused by dilated parauterine, paraovarian, and vaginal veins. PCS is typically characterized by ovarian venous incompetence that may be due to pelvic venous valvular insufficiency, hormonal factors, or mechanical venous obstruction. METHODS: We describe a case of a 38-year-old multiparous female with a history of pelvic pressure, vulvar varices, and dyspareunia. She underwent left gonadal vein coil embolization in 2014 for PCS that lead to symptomatic relief of her pain. Four years later, the patient returned for recurrent symptoms. Magnetic resonance venogram demonstrated dilated pelvic varices. The previously embolized left gonadal vein remained thrombosed, and there was no evidence of right gonadal vein insufficiency. However, catheter-based venography revealed a large, dilated, and incompetent median sacral vein. RESULTS: Pelvic venography demonstrated left gonadal vein embolization without any evidence of reflux. The right gonadal vein was also nondilated without reflux. Internal iliac venography showed large cross-pelvic collaterals and retrograde flow via a large, dilated median sacral vein. Coil embolization of the median sacral vein resulted in a dramatic reduction of pelvic venous reflux and resolution of symptoms. CONCLUSIONS: Recurrence of PCS can occur after ovarian vein embolization through other tributaries in the venous network. The median sacral vein is a rare cause of PCS. We present an interesting case of a successfully treated recurrent PCS with coil embolization of an incompetent median sacral vein.