Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN): An introduction to the Urinary Urgency Phenotyping Protocol LURN II.

AIMS: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls. METHODS: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies. RESULTS: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population. CONCLUSIONS: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency.

A Single Injection of Platelet-Rich Plasma Injection for the Treatment of Stress Urinary Incontinence in Females: A Randomized Placebo-Controlled Trial.

OBJECTIVE: To determine the efficacy of a single injection of platelet-rich plasma (PRP) into the anterior vaginal wall at the mid-urethra compared to placebo, as there is emerging evidence that PRP may help treat female stress urinary incontinence (SUI). METHODS: This was a single-blind, randomized, placebo-controlled clinical trial at a single institution. Females with bothersome, demonstrable stress-predominant urinary incontinence were enrolled. Participants were randomized to either injection of 5 mL autologous PRP or saline at the anterior vaginal wall at the mid-urethra. The primary outcome was composite treatment success at 6 months, defined as a negative cough stress test and an answer of "much better" or "very much better" on the Patient's Global Impression of Improvement. RESULTS: Fifty patients were enrolled in the study and randomized to the PRP group (n = 25) or the saline placebo group (n = 25). There was no statistically significant difference in the primary outcome between the 2 groups. Adverse events were minor, and the rate of adverse events was similar between both groups. CONCLUSION: In this randomized placebo-controlled study, we were unable to demonstrate a difference in SUI treatment success between PRP and saline injections. At this time, there is insufficient evidence to offer a one-time PRP injection into the anterior vaginal wall for treatment of female SUI.

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.

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

Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction. MATERIALS AND METHODS: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis. RESULTS: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2. CONCLUSIONS: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 +polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.

Early and recent exposure to adversity, TLR-4 stimulated inflammation, and diurnal cortisol in women with interstitial cystitis/bladder pain syndrome: A MAPP research network study.

Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder characterized by bladder and/or pelvic pain, and excessive urinary frequency and/or urgency. IC/BPS has been associated with high levels of ELA as well as a distinct inflammatory signature. However, associations between ELA and RLA with inflammatory mechanisms in IC/BPS that might underlie the link between adversity and symptoms have not been examined. Here we investigated ELA and RLA in women with IC/BPS as potential risk factors for inflammatory processes and hypothalamic-pituitaryadrenal (HPA) abnormalities using data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Women with IC/BPS and healthy controls (n = 154 and 32, respectively) completed surveys, collected salivary cortisol at awakening and bedtime for 3 days, and gave a blood sample which was analyzed for 7 LPS-stimulated cytokines and chemokines (IL-6, TNFα, IL-1ß, MIP1α, MCP1, IL-8, and IL-10). Two cytokine/chemokine composites were identified using principal components analysis. Patients with greater exposure to RLA or cumulative ELA and RLA of at least moderate severity showed elevated levels of a composite of all cytokines, adjusting for age, body mass index, and study site. Furthermore, there was a trending relationship between ELA and the pro-inflammatory composite score. Nocturnal cortisol and cortisol slope were not associated with ELA, RLA, or inflammation. The present findings support the importance of adverse events in IC/BPS via a biological mechanism and suggest that ELA and RLA should be assessed as risk factors for inflammation as part of a clinical workup for IC/BPS.

Significant financial differences of chemical and surgical androgen deprivation in a contemporary cohort.

Background: Androgen deprivation therapy (ADT) remains a cornerstone of treatment for advanced prostate cancer. Few men elect for surgical castration via bilateral orchiectomy. We sought to compare the relative difference in financial charges between chemical and surgical ADT in men. Methods: Billing data was obtained for patients with metastatic prostate cancer receiving chemical ADT and who had bilateral orchiectomy from 2014-2019. Men had chosen intervention based on personal preference. We compared charges of ADT administration for chemical ADT and overall charges for bilateral orchiectomy. We determined the time chemical ADT patient charges surpassed those of surgical charges, as well as the net present value (NPV) of hypothetical savings for electing surgery over various ADT agents. Results: One hundred and thirty-seven patients receiving chemical ADT and 7 patients who had undergone bilateral orchiectomy were analyzed. Median and mean surgical charges were $13,000. By 38 weeks following treatment initiation, 50% of chemical ADT patients had surpassed surgical charges, with 95% at 2 years. The NPV in savings for a median patient varied between ADT agent and was highest at $167,000 for leuprolide. Conclusions: In less than a year, the median chemical ADT patient charges were greater than surgical castration. The NPV of electing surgery over ADT was the highest with leuprolide. Despite under-utilization, surgical castration remains a medically appropriate and cost-effective option for permanent ADT.

Comparing clinical bladder diaries and recalled patient reports for measuring lower urinary tract symptoms in the symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Bladder diaries are a key source of information about lower urinary tract symptoms (LUTS); however, many patients do not complete them as instructed. Questionnaire-based patient-reported outcome measures (PROMs) are another option for reporting LUTS but may have recall bias. We assessed the strength of the associations between PROMs and a 3-day bladder diary. MATERIALS AND METHODS: Symptomatic adults from 6 tertiary care sites completed a 3-day paper bladder diary and 3-, 7-, and 30-day electronic PROMs. We assessed the linear associations between mapped pairs of diary variables and responses to PROM items using biserial and polyserial correlation coefficients with 95% confidence intervals. RESULTS: Of 290 enrolled participants, 175 (60%) completed the bladder diary as instructed and at least one corresponding PROM. Linear associations were strongest between the diary and 3-day recall of daytime frequency (r = 0.75) and nighttime frequency (r = 0.69), followed by voids with urgency sensations (r = 0.62), and an item reporting any incontinence (r = 0.56). Linear associations between bladder diary and specific incontinence variables (e.g., stress, urgency) were low to negligible (ranging from r = 0.16-0.39). Linear associations were consistent across the 3-, 7-, and 30-day recall periods. CONCLUSIONS: Missing and unusable bladder diary data were common, highlighting the patient burden associated with this method of data collection. A questionnaire-based PROM is a reasonable alternative to a diary for reporting voiding frequency and may offer an easier option for reporting some symptoms.

Long-Term Symptom Trajectories in Urologic Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

OBJECTIVE: To characterize Urologic Chronic Pelvic Pain Syndrome (UCPPS) pain and urinary symptom trajectories with up to 9 years of follow-up and evaluate whether initial 1-year trajectories are associated with longer-term changes. MATERIALS AND METHODS: Data were analyzed from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network's prospective observational protocols including the Epidemiology and Phenotyping Study (EPS; baseline to Year 1), EPS Extension (EXT; Years 1-5), and Symptom Patterns Study (SPS: 3-year study; Years 3-9). Adults with Interstitial Cystitis/Bladder Pain Syndrome or Chronic Prostatitis/Chronic Pelvic Pain Syndrome provided patient-reported assessments biweekly (EPS), every 4 months (EXT), or quarterly (SPS). Primary outcomes were composite pain (0-28) and urinary (0-25) severity scores. Multi-phase mixed effects models estimated outcomes over time, adjusted for baseline severity and stratified by EPS symptom trajectory. RESULTS: 163 participants (52% women; mean ± SD age 46.4 ± 16.1 years) completed EPS and enrolled in EXT; 67 also enrolled in SPS. Median follow-up was 4.6 years (range 1.3-9.0). After 1 year: 27.6%, 44.8% and 27.6% and 27.0%, 38.0% and 35.0% were improved, stable or worse in pain and urinary symptom severity, respectively. On average, pain and urinary symptom scores did not change further during EXT and SPS periods. CONCLUSIONS: Women and men with UCPPS showed remarkable stability in pain and urinary symptom severity for up to 9 years, irrespective of their initial symptom trajectory, suggesting UCPPS is a chronic condition with stable symptoms over multiple years of follow-up.

Flares and their impact among male urologic chronic pelvic pain syndrome patients: An in-depth qualitative analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

INTRODUCTION: There has been a sparse exploration of the lived experience of men with urologic chronic pelvic pain syndrome (UCPPS), and none with the goal of Investigating the experience of "flares" as part of this chronic pain syndrome in men. METHODS: We conducted three focus groups of male UCPPS patients at two sites of the MAPP Research Network (n = 16 total participants) to explore the full spectrum of flares and their impact on men's lives. RESULTS: Flare experiences were common and specific symptom components varied widely. Men reported nonpelvic symptoms (e.g., diarrhea), and variability in symptom intensity (mild to severe), duration (minutes to days), and frequency of flares. Flares episodes, and the threat of flares, were disruptive to their lives, social roles, and relationships. Distinct long-term impacts were reported, such as decreased sexual activity, decreased travel, and potential loss of employment or career. The themes included social isolation and the need for a sense of control and understanding over their unpredictable symptoms. CONCLUSIONS: Given their negative impact, future research with men and UCPPS should focus on approaches to prevent flares, and should consider a multimodal approach to reducing the frequency, severity, and/or duration. Quality of life may be improved by providing men with a sense of control over their symptoms and offering them multimodal treatment options, consistent with the recommendations for further research for women with UCPPS.

Clinical Phenotyping for Pain Mechanisms in Urologic Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

Three categories of pain mechanisms are recognized as contributing to pain perception: nociceptive, neuropathic, and nociplastic (ie, central nervous system augmented pain processing). We use validated questionnaires to identify pain mechanisms in Urologic Chronic Pelvic Pain Syndrome (UCCPS) patients (n = 568, female = 378, male = 190) taking part in the Symptom Patterns Study of the Multidisciplinary Approach to the study of chronic Pelvic Pain Research Network. A cutoff score of 12 on the painDETECT questionnaire (-1 to 38) was used to classify patients into the neuropathic category while the median score of 7 on the fibromyalgia survey criteria (0-31) was used to classify patients into the nociplastic category. Categories were compared on demographic, clinical, psychosocial, psychophysical and medication variables. At baseline, 43% of UCPPS patients were classified as nociceptive-only, 8% as neuropathic only, 27% as nociceptive+nociplastic, and 22% as neuropathic+nociplastic. Across outcomes nociceptive-only patients had the least severe symptoms and neuropathic+nociplastic patients the most severe. Neuropathic pain was associated with genital pain and/or sensitivity on pelvic exam, while nociplastic pain was associated with comorbid pain conditions, psychosocial difficulties, and increased pressure pain sensitivity outside the pelvis. A self-report method classifying individuals on pain mechanisms reveals clinical differences that could inform clinical trials and novel targets for treatment. PERSPECTIVE: This article presents differences in clinical characteristics based on a simple self-report method of classifying pain mechanisms for Urologic Chronic Pelvic Pain Syndrome patients. This method can be easily applied to other chronic pain conditions and may be useful for exploring pathophysiology in pain subtypes.

Daily symptom associations for urinary urgency and anxiety, depression and stress in women with overactive bladder.

INTRODUCTION AND HYPOTHESIS: Women with overactive bladder (OAB) report psychological distress, anxiety and depression, but short-term associations between these symptoms are poorly studied. Our objectives were to study daily associations between OAB symptoms and psychological symptoms and test whether these associations were stable when reassessed after 3 months. We hypothesized that OAB symptoms are positively associated with anxiety and depression symptoms over a short-term (daily) basis. METHODS: Female patients with OAB [bothersome urgency and/or urgency urinary incontinence (UUI)] assessed OAB and mood symptoms at baseline and 3 months using a 3-day bladder diary and visual analog scale (VAS) ratings (0-100 mm) for anxiety, depression and stress. Daily OAB and mood symptom associations were tested using Spearman correlations. Generalized estimating equation (GEE) models tested associations between daily urgency scores and each psychological rating adjusting for covariates, time and a time-symptom interaction term. RESULTS: Participants (n = 69) had mean (SD) age 63.3 (13.4) years. Baseline diary outcomes [median (IQR)/day] included day voids 8 (7-11), nocturia 0 (0-1), UUI episodes 1 (0-3) and urgency score 1.75 (1-2.25). Anxiety and depression diagnoses (dx) and treatment (tx) were common (anxiety dx 30.4%, tx 21.7%; depression dx 47.8%, tx 37.7%), but daily anxiety, depression and stress ratings were low [median (IQR) mm 10 (3-35), 5 (1-16), and 16 (4-39), respectively]. Daily urgency scores correlated with anxiety (r = 0.30-0.40, days 1-3, p ≤ 0.01 for all), depression (r = 0.24-0.35, p ≤ 0.05 all) and stress (r = 0.27-0.34, p ≤ 0.03 all). GEE models indicated no significant change in these associations between baseline and 3 months, and OAB treatment did not impact the associations. CONCLUSIONS: Urgency scores were positively associated with same-day ratings of anxiety, depression and stress in OAB patients.

Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications.

PURPOSE: The aim of our study was to elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles. MATERIALS AND METHODS: Paired bladder mucosal biopsies, 1 sample each from the Hunner lesion and nonlesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin and HIF1α; and quantitative polymerase chain reaction for IFN-α, IFN-ß, IFN-γ, TNF, TGF-ß1, HIF1α, IL-2, IL-4, IL-6, IL-10 and IL-12A. The results were compared between the lesion and nonlesion areas. RESULTS: RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (24) included HIF1α signaling pathway, PI3K-Akt signaling pathway, RAS signaling pathway and MAPK signaling pathway. By contrast, down-regulated pathways (6) included basal cell carcinoma and protein digestion and absorption. The mRNA levels of HIF1α, IFN-γ and IL-2, and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and nonlesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation and CD4/CD8 T-lymphocyte ratio. CONCLUSIONS: Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.

Overactive bladder phenotypes: development and preliminary data.

INTRODUCTION: The purpose of this study is to develop overactive bladder (OAB) phenotypes that can be used to develop diagnostic and treatment pathways and offer clues to the underlying etiologies of patients with OAB. MATERIALS AND METHODS: This is a retrospective, multicenter study of patients with lower urinary tract symptoms (LUTS). Evaluation included a 24-hour bladder diary (24HBD), the lower urinary tract symptoms score (LUTSS) questionnaire, uroflowmetry (Q), and post-void residual urine (PVR) measurement. Patients completed the 24HBD and LUTSS on a smartphone application or paper. Those with an OAB symptom sub-score (OABSS) ≥ 8 were included. An expert panel developed a phenotype classification system based on variables considered to be important for treatment. RESULTS: The following variables were selected for inclusion in the phenotype modeling: 24-hour voided volume (24HV), maximum voided volume (MVV), Qmax and PVR. Subjects were divided into three phenotypes based on the 24HV: polyuria (24HV > 2.5 L), normal (24 HV 1-2.5 L), and oliguria (24HV < 1 L). Each phenotype was subdivided based on MVV, Qmax & PVR, resulting in 18 sub-types. Five hundred thirty-three patients, 348 men and 185 women, completed the LUTSS and 24HBD. OAB was present in 399 (75%) - 261 men and 138 women. The prevalence of the primary phenotypes was polyuria (25%), normal (63%), and oliguria (11%). CONCLUSIONS: Classification of OAB variants into phenotypes based on 24HV, MVV, Qmax, and PVR provides the substrate for further research into the diagnosis, etiology, treatment outcomes and development of granular diagnostic and treatment algorithms.

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

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.