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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Believing women: a qualitative exploration of provider disbelief and pain dismissal among women with interstitial cystitis/bladder pain syndrome from the MAPP research network.

INTRODUCTION AND HYPOTHESIS: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters. METHODS: We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters. RESULTS: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine. CONCLUSIONS: The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required.

Food Sensitivities in a Diverse Nationwide Cohort of Veterans With Interstitial Cystitis/Bladder Pain Syndrome.

PURPOSE: Prior studies suggest that certain foods exacerbate interstitial cystitis/bladder pain syndrome symptoms. However, these studies were limited in size and demographics. We assessed the presence of diet sensitivities among patients with interstitial cystitis/bladder pain syndrome and compared them with patients with other pelvic pain conditions and healthy controls. MATERIALS AND METHODS: We identified Veterans Affairs patients nationwide by querying ICD-9/10 codes for interstitial cystitis/bladder pain syndrome. Patients were assigned to interstitial cystitis, other pelvic pain, or healthy control cohorts after chart review. We mailed all patients the Shorter-Moldwin Food Sensitivity Questionnaire to evaluate the self-perceived effects of specific foods/beverages on urinary symptoms and/or bladder pain. RESULTS: In the interstitial cystitis/bladder pain syndrome cohort, 70% had ≥1 food sensitivity vs 37% of the other pelvic pain cohort and 32% of healthy controls (P < .001). The average number of sensitivities were similar between other pelvic pain conditions and healthy control cohorts, which were significantly less than in interstitial cystitis/bladder pain syndrome patients. Interstitial cystitis/bladder pain syndrome patients were more sensitive to acidic, spicy foods, and certain beverages vs other cohorts (all P < .001). Within the interstitial cystitis/bladder pain syndrome cohort, Black patients had significantly higher sensitivity to alcoholic and noncaffeinated beverages than Whites. Black patients did report significantly worsened urinary urgency than Whites (P < .05). CONCLUSIONS: In a diverse population of veterans, interstitial cystitis/bladder pain syndrome patients had significantly more food sensitivities than those without interstitial cystitis/bladder pain syndrome. This suggests that food sensitivities could be suggestive of interstitial cystitis/bladder pain syndrome, which could make the Shorter-Moldwin Food Sensitivity Questionnaire a helpful diagnostic tool and aid in distinguishing interstitial cystitis/bladder pain syndrome from conditions often confused with interstitial cystitis/bladder pain syndrome.

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Validation of the 'Pelvic Pain Map': a new self-assessment tool for chronic pelvic pain localisation.

OBJECTIVE: To develop and validate the Pelvic Pain Map to fill a gap in the need for a localised body map of the pelvic region. PATIENTS AND METHODS: The Pelvic Pain Map incorporated input from 12 chronic pelvic pain experts across the United States, as well as patient feedback to assess face validity. Finalised diagrams are single, front-facing images of the male and female pelvis that incorporate both abdominal and perineal views. Assessment of test-retest reliability and construct (convergent and discriminant) validity was carried out on a retrospective cohort of patients with chronic pelvic pain syndrome (CPPS) who completed the maps from January 2022 to May 2022. Other measures used in the validation process consisted of the male and female forms of the Genitourinary Pain Index (GUPI) and the short form (six item) of the Pain Catastrophising Scale (PCS-6). RESULTS: Test-retest for individual map zones demonstrated moderate to excellent reliability (Cohen's kappa coefficients ranging from 0.28 to 0.64) and for total map zones demonstrated excellent reliability (intraclass correlation coefficient = 0.90). Convergent validity for individual map zones with location descriptors from the GUPI was strong (phi coefficients ranging from 0.26 to 0.79) and for total map zones was moderate (Spearman's correlation coefficient = 0.56). Discriminant validity for total map zones with separate, but related constructs from the GUPI and PCS-6 was weakly positive (Spearman's correlation coefficients ranging from 0.27 to 0.32). CONCLUSION: This study suggests that the Pelvic Pain Map is a valid and reliable tool for assessing location of pain in patients with CPPS. Our findings highlight the potential utility of the Pelvic Pain Map in guiding treatment selection and monitoring therapeutic response in patients with chronic pelvic pain.

Pelvic mapping to explore patterns of chronic pelvic pain.

PURPOSE: Chronic pelvic pain syndromes (CPPS) are commonly encountered by urologists and urogynecologists and pose diagnostic and therapeutic challenges. Body maps have been helpful adjuncts to verbal descriptions of pain and may serve a role in phenotyping what is known to be a heterogeneous patient population. The aim of this study was to assess whether patterns of pain as marked on a body map of the pelvis exist among common CPPS diagnoses. The secondary aim was to investigate the association between the total number of pain locations marked on the map and clinical indices in patients with 1 to 3 CPPS diagnoses. MATERIALS AND METHODS: Data was collected on patients who visited the Northwell Health Pelvic Pain Treatment Center (PPTC) from January to May 2022 and were diagnosed with at least one of four major CPPS diagnoses: interstitial cystitis/bladder pain syndrome (IC/BPS), pelvic floor myalgia (PFM), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and vulvodynia. Demographic data as well as survey data from pelvic pain maps, Genitourinary Pain Index (GUPI) forms, and the short form-6 of the Pain Catastrophizing Scale (PCS-6) were recorded. Descriptive statistics among CPPS groups and Pearson correlations among the number of CPPS diagnoses were computed. RESULTS: One hundred seventy females and 125 males with CPPS were included in the study. Significant cross-over in mapping patterns was notable between IC/BPS and PFM groups, both most commonly marking "abdomen" and "genital" regions. The most distinct pattern of pain was seen in patients with CP/CPPS and in patients with vulvodynia. Among the total sample, as the mean number of pain locations marked within the pelvis increased, GUPI and PCS scores increased (p < 0.05). As the number of CPPS diagnoses increased, the strength of the relationship independently increased. CONCLUSIONS: Pelvic body mapping demonstrated that different forms of CPPS displayed different distributions of pain, but mapping was not predictive of any diagnostic group. Nevertheless, the pelvic body map proved useful in identifying precise locations of pain and may help uncover regions of pain that cannot be easily communicated. The total number of pain sites marked appeared to correlate with worse clinical features.

Immune cell profiles of patients with interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder characterized by bladder pain upon filling which severely affects quality of life. Clinical presentation can vary. Local inflammatory events typify the clinical presentation of IC/BPS patients with Hunner lesions (IC/BPS-HL). It has previously been proposed that B cells are more prevalent in HL, but understanding their exact role in this environment requires a more complete immunological profile of HL. We characterized immunological dysfunction specifically in HL using immunohistochemistry. We detected significantly more plasma cells (50× increase, p < 0.0001), B cells (28× increase, p < 0.0001), T cells (3× increase, p < 0.0001), monocytes/macrophages (6× increase, p < 0.0001), granulocytes (4× increase, p < 0.0001), and natural killer cells (2× increase, p = 0.0249) in IC/BPS patients with HL than in unaffected controls (UC). Patients with IC/BPS-HL also had significantly elevated urinary levels of IL-6 (p = 0.0054), TNF-α (p = 0.0064) and IL-13 (p = 0.0304) compared to patients with IC/BPS without HL (IC/BPS-NHL). In contrast, IL-12p70 levels were significantly lower in the patients with HL than in those without these lesions (p = 0.0422). Different cytokines were elevated in the urine of IC/BPS patients with and without HL, indicating that different disease processes are active in IC/BPS patients with and without HL. Elevated levels of CD138+, CD20+, and CD3+ cells in HL are consistent B and T-cell involvement in disease processes within HL.

Is Pelvic Floor Muscle Tenderness a Distinct Urologic Chronic Pelvic Pain Syndrome Phenotype? Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Symptom Pattern Study.

PURPOSE: Of women with interstitial cystitis/bladder pain syndrome and men with chronic prostatitis/chronic pelvic pain syndrome 85% have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Research Network and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity in order to determine whether this is a phenotypic predictor in UCPPS. MATERIALS AND METHODS: Participants in the MAPP Network Symptom Patterns Study underwent a standardized pelvic examination (PEX). Trained examiners palpated 6 locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0, 1), mid (2, 3, 4, 5) and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires. RESULTS: The study cohort consisted of 562 UCCPS participants (375 females and 187 males) and 69 controls. Diagnoses included interstitial cystitis/bladder pain syndrome (397), chronic prostatitis/chronic pelvic pain syndrome (122), both (34) or no diagnosis (9). Of UCPPS participants 81% had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life and more widespread distribution of nonpelvic pain. CONCLUSIONS: UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life and a more centralized pain phenotype.

Reliability and Validity of Pain and Urinary Symptom Severity Assessment in Urological Chronic Pelvic Pain: A MAPP Network Analysis.

PURPOSE: We assessed the reliability and validity of an efficient severity assessment for pelvic pain and urinary symptoms in urological chronic pelvic pain syndrome, which consists of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 578 patients were assessed using brief, empirically derived self-report scales for pelvic pain severity (PPS) and urinary symptom severity (USS) 4 times during a 1-month period and baseline clinic visit that included urological, pain and illness-impact measures. Mild, moderate and severe categories on each dimension were examined for measurement stability and construct validity. RESULTS: PPS and USS severity categories had adequate reliability and both discriminant validity (differential relationships with specific clinical and self-report measures) and convergent validity (common association with nonurological somatic symptoms). For example, increasing PPS was associated with pelvic tenderness and widespread pelvic pain, whereas USS was associated with urgency during a bladder filling test and increased sensory sensitivity. PPS and USS categories were independently associated with nonurological pain and emotional distress. A descriptive analysis identified higher likelihood characteristics associated with having moderate to severe PPS or USS or both. Lack of sex interactions indicated that the measures are comparable in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. CONCLUSIONS: Women and men with urological chronic pelvic pain syndrome can be reliably subgrouped using brief self-report measures of mild, moderate or severe pelvic pain and urinary symptoms. Comparisons with a broad range of clinical variables demonstrate the validity and potential clinical utility of these classifications, including use in clinical trials, health services and biological research.

Safety, tolerability, and efficacy of LiRIS 400 mg in women with interstitial cystitis/bladder pain syndrome with or without Hunner lesions.

AIMS: Two phase 2 studies were conducted to assess the efficacy and safety of lidocaine-releasing intravesical system (LiRIS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with (Study 001; NCT02395042) or without, (Study 002; NCT02411110) Hunner lesions (HL). METHODS: Both were multicenter, randomized, double-blind, placebo-controlled, and enrolled women aged ≥18 years. In Study 001, patients were randomized 2:1:1 to LiRIS 400 mg/LiRIS 400 mg, placebo/LiRIS 400 mg, or placebo/placebo for a continuous 28 (2 × 14)-day period. In Study 002, patients were randomized 1:1 to LiRIS 400 mg or placebo for a continuous (single treatment) 14-day period. RESULTS: In total, 59 and 131 patients received treatment in Studies 001 and 002, respectively. There was no statistically significant difference in the primary endpoint, the change from baseline to Week 4 of follow-up post-removal in mean daily average bladder numeric rating scale (NRS) pain score in either study (Study 001: placebo/placebo, -1.6; LiRIS/LiRIS, -2.7, p = 0.142; placebo/LiRIS, -2.5, p = 0.319; Study 002: LiRIS -1.2; placebo, -1.5, p = 0.505). There was no statistically significant difference between groups in daily worst NRS pain score, number of micturitions/day or urgency episodes/day. There was no clear trend for reduction in number of HL for LiRIS vs placebo. The frequency of treatment-emergent adverse events was similar between treatment groups in both studies; most were mild or moderate intensity. CONCLUSION: These studies did not demonstrate a treatment effect of LiRIS 400 mg compared with placebo, either in patients with IC/BPS with HL, or in those without HL.

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.

Targeting the SHIP1 Pathway Fails to Show Treatment Benefit in Interstitial Cystitis/Bladder Pain Syndrome: Lessons Learned from Evaluating Potentially Effective Therapies in This Enigmatic Syndrome.

PURPOSE: In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: Subjects with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point scale despite treatment were randomized to 100 or 200 mg of an oral SHIP1 activator or placebo once daily for 12 weeks. Maximum pain scores and urinary frequency were recorded in an e-diary. The ICSI (O'Leary-Sant Interstitial Cystitis Symptom Index) and BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) questionnaires were administered. Safety was monitored through 12 weeks of treatment. RESULTS: A total of 298 female subjects with moderate to severe symptoms of interstitial cystitis/bladder pain syndrome were treated with 100 or 200 mg SHIP1 activator orally once daily for 12 weeks. Treatment demonstrated no difference in maximum daily bladder pain compared to placebo. There was no treatment benefit over that of placebo in the secondary end points of urinary voiding frequency, the BPIC-SS, the ICSI and a global response assessment. Exploratory analysis in 87 male subjects yielded a similar result, that is no difference from placebo. Treatment was generally well tolerated at both doses. CONCLUSIONS: SHIP1 activation is a safe but ineffective therapeutic approach to interstitial cystitis/bladder pain syndrome. Although this was a negative trial, the important lessons learned from this study in respect to inflammatory phenotype differentiation, including the potential importance of cystoscopy based classification, will improve current treatment in patients with interstitial cystitis/bladder pain syndrome and allow for better future trial design in those with this difficult urological chronic pain syndrome.

Depression and Coping Behaviors Are Key Factors in Understanding Pain in Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a urologic chronic pelvic pain syndrome with suboptimal treatment outcomes. Catastrophizing is an empirically supported risk factor for greater IC/BPS pain. AIMS: In this study, a moderated multiple mediation model is tested in which several additional psychosocial risk factors (depression, illness and wellness-focused behavioral coping strategies) are proposed as mediators or moderators in the existing relationship between catastrophizing and IC/BPS pain. DESIGN: The present questionnaire study employed a cross-sectional design. SETTINGS AND PARTICIPANTS: Female patients with an IC/BPS diagnosis (n = 341) were recruited at tertiary care sites. METHODS: Participants completed questionnaires assessing pain, catastrophizing, behavioral coping strategies, and depressive symptoms. Aggregate factor scores were calculated following exploratory factor analyses. RESULTS: It was found that patients with a greater tendency to catastrophize were more likely to engage in illness-focused coping strategies, which contributed to the reporting of greater sensory and affective pain. Furthermore, this mediating effect of illness-focused coping on affective pain was more likely to occur in those patients reporting greater depressive symptoms. CONCLUSIONS: Illness-focused behavioral coping is an important mechanism between maladaptive pain cognition and aspects of patient pain, with patients reporting greater depressive symptoms at increased risk for elevated pain. Patient management techniques, including screening for catastrophizing, coping, and depression, are recommended to enrich IC/BPS management.

Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

OBJECTIVES: To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. PATIENTS AND METHODS: The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. RESULTS: An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. CONCLUSIONS: The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability.

Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.

PURPOSE: The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome based upon data received since the publication of original guideline in 2011. MATERIALS AND METHODS: A systematic literature review using the MEDLINE(®) database (search dates 1/1/83-7/22/09) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of IC/BPS. This initial review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. The AUA update literature review process, in which an additional systematic review is conducted periodically to maintain guideline currency with newly published relevant literature, was conducted in July 2013. This review identified an additional 31 articles, which were added to the evidence base of this Guideline. RESULTS: Newly incorporated literature describing the treatment of IC/BPS was integrated into the Guideline with additional treatment information provided as Clinical Principles and Expert Opinions when insufficient evidence existed. The diagnostic portion of the Guideline remains unchanged from the original publication and is still based on Expert Opinions and Clinical Principles. CONCLUSIONS: The management of IC/BPS continues to evolve as can be seen by an expanding literature on the topic. This document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient. As the science relevant to IC/BPS evolves and improves, the strategies presented will require amendment to remain consistent with the highest standards of care.

Statistical validation of the shorter-moldwin food sensitivity questionnaire for patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: American Urological Association guidelines suggest dietary changes as first line treatment for interstitial cystitis/bladder pain syndrome. We previously developed a validated survey instrument to determine which foods, beverages and supplements exacerbate the symptoms of this condition. In this study we developed a shortened questionnaire that would provide an easily self-administered food symptom history useful for clinical practice and future research. MATERIALS AND METHODS: Using data from our previously validated food sensitivity questionnaire we remodeled the original lengthy survey to an abbreviated list including the 35 most problematic comestibles. The instrument was reviewed by a panel of experts for face and content validity, and tested for internal consistency, readability and clarity, and test-retest reliability. RESULTS: Of the 124 patients who completed a baseline questionnaire 52 (42%) returned the second instrument 1 week after completing the first instrument. Internal consistency was high (α=0.96). A total of 47 patients (90.4%) indicated that they were food sensitive. Questionnaire test-retest reliability assessed by the Spearman correlation coefficient ranged from moderate (ρ=0.48 for Equal®) to very strong (ρ=0.90 for beer). Discrepancies between the survey instruments in individual comestibles occurred only 1% of the time. CONCLUSIONS: Our short form diet history questionnaire based on a previously validated long form is a reliable, newly validated instrument that will help identify comestibles associated with interstitial cystitis/bladder pain syndrome symptoms. Its brevity makes it simple to administer and useful for dietary management in this population.

Understanding the sleep-pain relationship in patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition with critical symptoms of urinary urgency and frequency, persistent bladder-related pain, and reduced quality of life. Poor-quality sleep can lead to significant disturbances in daily life and increased pain in IC/BPS patients. Resilience, depressive symptoms, and pain catastrophizing have univariate associations with sleep and pain in IC/BPS, suggesting they may be mechanisms in this sleep and pain relationship. METHODS: This online study recruited patients self-reporting a diagnosis of IC/BPS through support groups, social media posts (Facebook, Reddit, and Instagram), and urology clinic advertisements. Participants completed questionnaires on demographics, urologic symptoms, pain, pain catastrophizing, depressive symptoms, and resilience. Only those participants who met the RAND Interstitial Cystitis Epidemiology (RICE) criteria for IC/BPS diagnosis were included. A multiple mediation model was first examined, followed by a serial mediation model. RESULTS: Seventy-four participants (Mage= 47.0, standard deviation [SD ] 16.7, range 18-83 years) met inclusion criteria. A multiple mediation model showed greater sleep disturbance was associated with greater pain severity through depressive symptoms and pain catastrophizing, but not resilience (b=0.79, bootSE =0.26, bootCI [0.33, 1.35]). A serial mediation showed that the sleep-to-pain relationship had a significant indirect effect through pain catastrophizing and depressive symptoms (b=0.78, bootSE =0.26, bootCI [0.35, 1.32]). CONCLUSIONS: Findings suggest depressive symptoms and pain catastrophizing may be important psychosocial mechanisms in the sleep-to-pain relationship. These results help guide future sleep and pain research in IC/BPS and aid in developing and refining treatments.

Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis.

Hemorrhagic cystitis may be induced by infection, radiation therapy, or medications or may be idiopathic. Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.