Urologic Chronic Pelvic Pain Research Articles

Letter: Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-analysis of the Peer-reviewed Flare Literature

Letter: Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-analysis of the Peer-reviewed Flare Literature

Therapeutic Approaches for Urologic Chronic Pelvic Pain Syndrome; Management: Research Advances, Experimental Targets, and Future Directions.

Urologic chronic pelvic pain syndrome (UCPPS) is a painful chronic condition with persistent pain originating from the pelvis that often leads to detrimental lifestyle changes in the affected patients. The syndrome develops in both sexes, with an estimated prevalence of 5.7% to 26.6% worldwide. This narrative review summarizes currently recommended therapies for UCPPS, followed by the latest animal model findings and clinical research advances in the field. The diagnosis of UCPPS by clinicians has room for improvement despite the changes in the past decade aiming to decrease the time to treatment. Therapeutic approaches targeting growth factors (i.e., nerve growth factor, vascular endothelial growth factor), amniotic bladder therapy, and stem cell treatments gain more attention as experimental treatment options for UCPPS. The development of novel diagnostic tests based on the latest advances in urinary biomarkers would be beneficial to assist with the clinical diagnosis of UCPPS. Future research directions should address the role of chronic psychologic stress and the mechanisms of pain refractory to conventional management strategies in UCPPS etiology. Testing the applicability of cognitive behavioral therapy in this cohort of UCPPS patients might be promising to increase their quality of life. The search for novel lead compounds and innovative drug delivery systems requires clinically relevant translational animal models. The role of autoimmune responses triggered by environmental factors is another promising research direction to clarify the impact of the immune system in UCPPS pathophysiology. SIGNIFICANCE STATEMENT: This minireview provides an up-to-date summary of the therapeutic approaches for UCPPS with a focus on recent advancements in the clinical diagnosis and treatments of the disease, pathophysiological mechanisms of UCPPS, signaling pathways, and molecular targets involved in pelvic nociception.

(213) Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review Regarding Anxiety and Depression

Abstract Introduction Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a urologic chronic pelvic pain syndrome with an unknown etiology and a variety of somatic and psychological symptoms, including elevated levels of anxiety and depression (Crawford, 2019). This often causes substantial impairment to quality of life: it is well known that unaddressed psychosocial elements of chronic pain can shape patient perceptions and behavior, and are associated with poorer functioning, adjustment, prognosis, and response to treatment (Piontek et al., 2022). Investigating the role of psychosocial factors in IC/BPS increase over the last years; however, prior to the last 5 years, there had been a scarcity of research on psychosocial factors compared to that in similar conditions (Windgassen et al., 2020). Objective Despite recommendations for the inclusion of non-pharmacological treatment in the management of IC/BPS, the focus so far has predominantly been on the inclusion of physical therapies with minimal discussion of psychological interventions. Therefore, this review aimed to examine the most recent studies regarding anxiety and depression in patients with IC/BPS, to stress the urgency of considering multidisciplinary care for individuals with this debilitating condition. Methods A literature search (PubMed and Google Scholar) of the past 5 years (January 2018 – March 2023) was conducted using key words related to IC/BPS, anxiety and depression, e.g., “(Interstitial cystitis OR Bladder pain syndrome) AND (Anxiety OR Depression OR Depressive disorder OR Psychology)”. The inclusion criteria were: to be empirical studies, to have been published within the last 5 years, to have included in the protocol measurements of anxiety and/or depression. A total of 28 studies were selected. Results There is a high rate of psychosocial comorbidities in IC/BPS; in particular, elevated levels of anxiety and depression, which are highly correlated with each other and with pain intensity. In addition, pain catastrophizing and helplessness seem to have a key role in the maintenance of the negative relationship between depression and pain over time in IC/BPS. Thus, there appears to be a complex interaction between psychopathologic and somatic symptoms. We assume that changes in mood and anxiety share a bidirectional relationship with IC/BPS pain severity: if pain increases, mood and anxiety likely worsen and, similarly, if mood and anxiety worsen it predicts an increased level of pain will follow. Conclusions IC/BPS is a complex condition that requires a management plan beyond the biomedical approach. Indeed, the psychological impact of IC/BPS is pervasive and severe. Our review supports the findings of previous studies that showed patients with this condition have a significantly higher risk of experiencing mental-emotional disorders compared to those without. These findings further strengthen the evidence base showing that anxiety and depression may not only be a consequence of this chronic pain condition but may also be involved in its maintenance. Our results suggest that it is crucial addressing anxiety and depression as early as possible in biopsychosocially oriented therapeutic interventions for patients with IC/BPS. Therefore, it is recommended that health care providers conduct a thorough assessment of this condition to identify therapeutic goals to pursue and possibly consider a multidisciplinary approach. Disclosure No.

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data

BackgroundUrologic chronic pelvic pain syndrome (UCPPS), which includes interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP/CPPS), is associated with increased voiding frequency, nocturia, and chronic pelvic pain. The cause of these diseases is unknown and likely involves many different mechanisms. Dysregulated renin-angiotensin-aldosterone-system (RAAS) signaling is a potential pathologic mechanism for IC/BPS and CP/CPPS. Many angiotensin receptor downstream signaling factors, including oxidative stress, fibrosis, mast cell recruitment, and increased inflammatory mediators, are present in the bladders of IC/BPS patients and prostates of CP/CPPS patients. Therefore, we aimed to test the hypothesis that UCPPS patients have dysregulated angiotensin signaling, resulting in increased hypertension compared to controls. Secondly, we evaluated symptom severity in patients with and without hypertension and antihypertensive medication use.MethodsData from UCPPS patients (n = 424), fibromyalgia or irritable bowel syndrome (positive controls, n = 200), and healthy controls (n = 415) were obtained from the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain I (MAPP-I). Diagnosis of hypertension, current antihypertensive medications, pain severity, and urinary symptom severity were analyzed using chi-square test and t-test.ResultsThe combination of diagnosis and antihypertensive medications use was highest in the UCPPS group (n = 74, 18%), followed by positive (n = 34, 17%) and healthy controls (n = 48, 12%, p = 0.04). There were no differences in symptom severity based on hypertension in UCPPS and CP/CPPS; however, IC/BPS had worse ICSI (p = 0.031), AUA-SI (p = 0.04), and BPI pain severity (0.02). Patients (n = 7) with a hypertension diagnosis not on antihypertensive medications reported the greatest severity of pain and urinary symptoms.ConclusionThis pattern of findings suggests that there may be a relationship between hypertension and UCPPS. Treating hypertension among these patients may result in reduced pain and symptom severity. Further investigation on the relationship between hypertension, antihypertensive medication use, and UCPPS and the role of angiotensin signaling in UCPPS conditions is needed.

Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site. Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations. These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.

Ecological momentary assessment of pelvic pain and urinary urgency variability in urologic chronic pelvic pain syndrome and their association with illness impact and quality of life: Findings from the multidisciplinary approach to the study of chronic pelvic pain symptom patterns study.

This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). A previously validated smart phone app (M-app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M-app notifications were sent 4-times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined. A total of 204 participants enrolled in the M-app study (64% female). M-app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability. PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses.

Cognitive Behavioral Therapy for Chronic Pelvic Pain: What Is It and Does It Work?

Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome in women and men and chronic prostatitis/chronic pelvic pain syndrome in men, is a common, often disabling urological disorder that is neither well understood nor satisfactorily treated with medical treatments. The past 25 years have seen the development and validation of a number of behavioral pain treatments, of which cognitive behavioral therapy (CBT) is arguably the most effective. CBT combines strategies of behavior therapy, which teaches patients more effective ways of behaving, and cognitive therapy, which focuses on correcting faulty thinking patterns. As a skills-based treatment, CBT emphasizes "unlearning" maladaptive behaviors and thoughts, and replacing them with more adaptive ones that support symptom self-management. This review describes the rationale, technical procedures, and empirical basis of CBT. While evidence supports CBT for treatment-refractory chronic pain disorders, there is limited understanding of why or how CBT might work, for whom it is most beneficial, or the specific UCPPS symptoms (eg, pain, urinary symptoms) it effectively targets. This is the focus of EPPIC (Easing Pelvic Pain Interventions Clinical Research Program), a landmark NIH trial examining the efficacy of low-intensity, home-based CBT for UCPPS relative to a nonspecific comparator featuring self-care recommendations of AUA guidelines. Systematic efforts to increase both the efficiency of CBT and the way it is delivered (eg, home-based treatments) are critical to scaling up CBT, optimizing its therapeutic potential, and reducing the public health burden of UCPPS.

Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

Links between brain neuroimaging and blood inflammatory markers in urological chronic pelvic pain syndrome

Urological chronic pelvic pain syndrome (UCPPS) is a debilitating painful condition with unclear etiology. Prior researchers have indicated that compared to healthy controls, patients with UCPPS demonstrated altered brain activity. Researchers have also shown that in UCPPS, several blood inflammatory markers relate to clinical variables of pain, fatigue, and pain widespreadness. However, how altered brain function in patients with UCPPS relates to blood inflammation remains unknown. To extend and connect prior findings of altered brain function and inflammatory factors in UCPPS, we conducted a secondary analysis of data from a cohort of UCPPS patients (N = 29) and healthy controls (N = 31) who provided both neuroimaging and blood data (National Institute of Health MAPP Research Network publicly available dataset). In our present study, we aimed to evaluate relationships between a priori-defined brain neuroimaging markers and inflammatory factors of interest and their relationships to pain-psychological variables. We hypothesized that two brain alterations of interest (i.e., PCC – left hippocampus functional connectivity and PCC – bilateral amygdala functional connectivity) would be correlated with four cytokine markers of interest: interleukin (IL) – 6, tumor necrosis factor-alpha (TNF-a), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the UCPPS cohort, we identified a significant PCC - left hippocampus functional connectivity relationship with IL-6 (p = 0.0044). Additionally, in the UCPPS cohort, we identified a PCC - amygdala functional connectivity relationship with GM-CSF which did not meet our model's threshold for statistical significance (p = 0.0665). While these data are preliminary and cross-sectional, our findings suggest connections between brain function and levels of low-grade systemic inflammation in UCPPS. Thus, while further study is needed, our data indicate the potential for advancing the understanding of how brain functional circuits may relate to clinical symptoms and systemic inflammation.

Maximizing Training and Mentorship in Sex as a Biological Variable Research Across Different Brain-Body Disorders.

The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different organs and the brain in health and disease with a strong focus on sex as a biological variable (SABV). While the initial focus was on brain-gut interactions in irritable bowel syndrome (IBS), one of the most common disorders of gut-brain interaction, the scope of our Center's research has expanded to a range of different diseases, including inflammatory bowel disease, alcohol use disorder, obesity, urological chronic pelvic pain syndrome, and vulvodynia. This expansion of research focused on the role of brain-body and brain-gut microbiome interactions in these various disorders, aligning well with the increasing importance of multidisciplinary and interdisciplinary team science. The SCORE's Career Enhancement Core (CEC) has modeled team science as applied to SABV research, with educational and training opportunities, a mentoring program, seed grant funding, and other career development experiences that enable mentees to work across the disciplines involved in brain body research. The CEC goals are: (1) To provide seed grant funds for innovative research relevant to the overall SCORE mission and research program; (2) to recruit and foster the career development of students, trainees, and junior investigators who conduct research focused on sex differences or women's health in IBS and chronic constipation and other brain-gut disorders; (3) to facilitate and promote collaboration between the UCLA SCORE and other academic programs involved in women's health education and research; and (4) to promote the importance of SABV through community outreach using collaborative and innovative approaches. These goals focus on establishing the leading research center in sex differences in basic, translational, and clinical aspects of brain-body interactions and on providing women and underrepresented individuals with research opportunities needed to become independent investigators.

Neurobiology and long-term impact of bladder-filling pain in humans: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network study.

Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.

Mediators of the association between childhood trauma and pain sensitivity in adulthood: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network analysis.

Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network's Symptom Pattern Study to investigate the impact of childhood sexual and nonsexual violent trauma on pelvic and nonpelvic pain sensitivity among adult patients with UCPPS, as well as potential mediators of this association. Study participants who met inclusion criteria for UCPPS completed questionnaires assessing childhood and recent trauma, affective distress, cognitive dysfunction, and generalized sensory sensitivity. Experimental pain sensitivity was also evaluated using standardized pressure pain applied to the pubic region and the arm. Bivariate analyses showed that childhood violent trauma was associated with more nonviolent childhood trauma, more recent trauma, poorer adult functioning, and greater pain sensitivity at the pubic region, but not pain sensitivity at the arm. Path analysis suggested that childhood violent trauma was indirectly associated with pain sensitivity at both sites and that this indirect association was primarily mediated by generalized sensory sensitivity. More experiences of recent trauma also contributed to these indirect effects. The findings suggest that, among participants with UCPPS, childhood violent trauma may be associated with heightened pain sensitivity to the extent that trauma history is associated with a subsequent increase in generalized sensory sensitivity.

MP15-07 UROLOGIC CHRONIC PELVIC PAIN ASSESSMENT USING THE NUMERIC RATING SCALE AND DEFENSE VETERANS RATING SCALE

You have accessJournal of UrologyCME1 Apr 2023MP15-07 UROLOGIC CHRONIC PELVIC PAIN ASSESSMENT USING THE NUMERIC RATING SCALE AND DEFENSE VETERANS RATING SCALE William Shyr, Kelli Aibel, Eric Macdonald, Karen Huang, and Robert Moldwin William ShyrWilliam Shyr More articles by this author , Kelli AibelKelli Aibel More articles by this author , Eric MacdonaldEric Macdonald More articles by this author , Karen HuangKaren Huang More articles by this author , and Robert MoldwinRobert Moldwin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pain scores are essential tools used to assess urologic chronic pelvic pain (UCPP). The Numeric Rating Scale (NRS) rates pain on a 0-10 numeric scale. The Defense and Veterans Pain Rating Scale (DVPRS) is a newly designed and validated pain scale that improves upon the NRS by incorporating faces, color-coded bars, and quality-of-life (QoL) descriptors that correspond to each pain level from 0-10. To our knowledge, the use of DVPRS in patients with UCPP has not been described within the literature. We studied the relationship between the NRS and DVPRS in patients with UCPP. METHODS: We retrospectively reviewed the charts of 107 patients with UCPP, including interstitial cystitis, bladder pain syndrome, pelvic floor myalgia, vulvodynia, and chronic prostatitis/chronic pelvic pain syndrome. Patients completed validated survey instruments, including the NRS, DVPRS, and pain catastrophizing score (PCS). The NRS and DVPRS were correlated using the Spearman correlation coefficient. The Wilcoxon signed-rank test was used to analyze the differences between the pain scales. We also analyzed pain levels in relation to sociodemographic data and comorbidities, such as back pain, fibromyalgia, anxiety, and depression. RESULTS: The median patient age was 58. The NRS and DVPRS were positively correlated with each other (R=0.77; p<0.001) (Figure 1). Both scales were negatively correlated with age, but the association was not significant (NRS: R=–0.10, p=0.30; DVPRS: R=–0.14, p=0.13). The differences in pain scores, defined as NRS minus DVPRS, ranged from -4 to 5, with one potential outlier of 5. However, the Wilcoxon signed-rank test showed no significant differences in pain scores across the two scales (p=0.57). When pain level was categorized into low (0-3), moderate (4-7), and high (8-10), the NRS and DVPRS had no significant associations with pain severity, sex, and comorbidities. CONCLUSIONS: Our findings demonstrated that both scales are strongly correlated with no significant differences. Given that the DVPRS relates each pain level to QoL measures, our study suggests that UCPP patients likely take their QoL into account when rating their pain levels on the NRS. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e194 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Shyr More articles by this author Kelli Aibel More articles by this author Eric Macdonald More articles by this author Karen Huang More articles by this author Robert Moldwin More articles by this author Expand All Advertisement PDF downloadLoading ...

High Fat/High Sucrose Diet Consumption Worsens Comorbid Metabolic Outcomes In An Early Life Stress Model Of Urologic Chronic Pelvic Pain In Mice

High Fat/High Sucrose Diet Consumption Worsens Comorbid Metabolic Outcomes In An Early Life Stress Model Of Urologic Chronic Pelvic Pain In Mice

A Bibliometric Analysis of Urologic Chronic Pelvic Pain Syndrome From 2000 to 2022.

Urologic chronic pelvic pain syndrome has attracted a lot of attention in the new century, and an increasing number of relevant studies have been published. Therefore, we performed a bibliometric analysis of these publications, hoping to show the current research hotspots and future research trends. The articles on were selected from the Web of Science Core Collection. Countries, authors, references and keywords in the field were visualized and analyzed using CiteSpace and VOSViewer software. A total of 1014 articles on urologic chronic pelvic pain syndrome were identified, with "chronic pelvic pain syndrome" being the most common keyword, with a strong association with "interstitial cystitis" and "chronic prostatitis". The hotspot of urologic chronic pelvic pain syndrome research has gradually shifted from chronic prostatitis / urologic chronic pelvic pain syndrome to cystitis/bladder pain syndrome over the past few years. Future research tends to focus on urologic chronic pelvic pain syndrome etiology, including oxidative stress and inflammation. Research on urologic chronic pelvic pain syndrome is steadily growing. The United States has made the most prominent contribution in this area, and the share of China's contribution is expected to grow further. The etiology of urologic chronic pelvic pain syndrome, including inflammation and oxidative stress, have been the focus of current research and developmental trends in the future research.

Clinically Important Differences for Pain and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study.

Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity. An absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms. A reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

Associations Between Urological Chronic Pelvic Pain Syndrome Symptom Flares, Illness Impact, and Health Care Seeking Activity: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study.

Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients). We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels. Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized β coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized β coefficients=0.11-0.25). Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-β/SMAD pathways. Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Reproducible Microstructural Changes in the Brain Associated With the Presence and Severity of Urologic Chronic Pelvic Pain Syndrome (UCPPS): A 3-Year Longitudinal Diffusion Tensor Imaging Study From the MAPP Network

Microstructural alterations have been reported in patients with urologic chronic pelvic pain syndrome (UCPPS). However, it isn't clear whether these alterations are reproducible within 6 months or whether long-term symptom improvement is associated with specific microstructural changes. Using data from the MAPP-II Research Network, the current study performed population-based voxel-wise DTI and probabilistic tractography in a large sample of participants from the multicenter cohort with UCPPS (N = 364) and healthy controls (HCs, N = 61) over 36 months. While fractional anisotropy (FA) differences between UCPPS patients and HCs were observed to be unique at baseline and 6-month follow-up visits, consistent aberrations in mean diffusivity (MD) were observed between UCPPS and HCs at baseline and repeated at 6 months. Additionally, compared to HCs, UCPPS patients showed stronger structural connectivity (SC) between the left postcentral gyrus and the left precuneus, and weaker SC from the left cuneus to the left lateral occipital cortex and the isthmus of the left cingulate cortex at baseline and 6-month. By 36 months, reduced FA and MD aberrations in these same regions were associated with symptom improvement in UCPPS. Together, results suggest changes in white matter microstructure may play a role in the persistent pain symptoms in UCPPS. PerspectiveThis longitudinal study identified reproducible, “disease-associated” patterns in altered mean diffusivity and abnormal microstructural connectivity in UCPPS comparing to HCs over 6 months. These differences were found in regions involved in sensory processing and integration and pain modulation, making it potentially amenable for clinical interventions that target synaptic and/or neuronal reorganization.

Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

BackgroundSexual dysfunction (SD), including erectile (ED) and ejaculatory dysfunction, is associated with diminished quality of life (QoL) in men with UCPPS (chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and/or interstitial cystitis/bladder pain syndrome (IC/BPS)). AimWe sought to compare SD among male patients with UCPPS, other chronic pain conditions (positive controls, PC), and healthy controls (HC) without chronic pain, and to evaluate the association of comorbidities, psychosocial factors, and urologic factors of SD in all 3 groups. MethodsBaseline data from male UCPPS participants, PC (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and HC enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Epidemiology and Phenotyping Study were included in the analysis. Sexual function was assessed using the International Index of Erectile Function-Erectile Function Domain (IIEFEF) and Ejaculatory Function Scale (EFS). Male ED was defined as a composite IIEF-EF score <21. Higher EFS score indicated worse sexual dysfunction; no threshold to define SD was identified for the EFS. Multivariable logistic and linear regression was used to investigate associations of comorbidities, psychosocial factors, and urologic factors with ED and ejaculatory, respectively. OutcomesComorbidities, genital pain, and psychosocial factors are associated with SD across the study population and male patients with UCPPS had a high prevalence of ED and greater ejaculatory dysfunction. ResultsThere were 191 males with UCPPS; 44 PC; and 182 HC. Males with UCPPS had worse SD compared to PC and HC including lower mean IIEF-EF scores, greater degree of ejaculatory dysfunction, and lower quality of sexual relationships. Among all 3 cohorts, depression, stress, and pain were associated with ED in univariable and multivariable analysis, as was diabetes mellitus. Pain in the genitalia, severity of urinary symptoms, depression, stress, and history of childhood sexual trauma were associated with ejaculatory dysfunction in univariable and multivariable analysis. Clinical ImplicationsA multidisciplinary approach that addresses the identified risk factors for SD may improve overall QoL in males with UCPPS. Strengths and LimitationsOur study is strengthened by its use of validated, patient-reported questionnaires and inclusion of healthy and positive controls. Our understanding of the role of IC in this study is limited because only 1 patient in the study had IC/BPS as a sole diagnosis. ConclusionsWhen compared to healthy controls and patients with other chronic pain conditions, males with UCPPS experience higher degrees of SD, including erectile and ejaculatory dysfunction.Loh-Doyle JC, Stephens-Shields AJ, Rolston R, et al. Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. J Sex Med 2022;19:1804–1812.