Publications

137 Publications from 2009 – 2024:

2024

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Study.

Authors: Farrar JT, Locke KT Jr., Clemens JQ, Griffith JW, Harte SE, Kirkali Z, Kreder KJ, Krieger JN, Lai HH, Moldwin RM, Mullins C, Naliboff BD, Pontari MA, Rodriguez LV, Schaeffer AJ, Schrepf A, Stephens-Shields A, Sutcliffe S, Taple BJ, Williams DA, Landis JR. 
Accepted: PAIN

Abstract

Abstract

[coming soon]

Brain predicted age in chronic pelvic pain: A study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network

Format: Research Paper
Authors: Kristan A Leech; Sarah A Kettlety; Wendy J Mack; Karl Kreder; Andrew Schrepf; Jason J Kutch
Accepted: PAIN

Abstract

Abstract

[coming soon]

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.

Erickson BA, Griffith JW, Wensheng G, Mengying Y, Herman T, Bradley CS, Quentin Clemens J, Farrar JT, Gupta P, Kreder KJ, Henry Lai H, Naliboff BD, Newman DK, Rodriguez LV, Spitznagle T, Sutcliffe S, Sutherland SE, Taple BJ, Richard Landis J. 
Neurourol Urodyn. 2024 Apr;43(4):893-901. doi: 10.1002/nau.25363. Epub 2024 Jan 22. [PMID: 38247366] [PMC11031348]

Abstract

Abstract

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.

Keywords: ecological momentary assessment; illness impact; phone application; quality of life; urologic chronic pelvic pain syndrome; variability.

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

Barker ES, Chiu K, Brown VL, Morsy H, Yaeger LH, Catna A, Pakpahan R, Moldwin R, Shorter B, Lowder JL, Lai HH, Sutcliffe S.
J Urol. 2024 Mar;211(3):341-353. doi: 10.1097/JU.0000000000003820. Epub 2023 Dec 18. [PMID: 38109700 Review] [PMC11037930]

Abstract

Abstract

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.

Keywords: bladder pain syndrome; chronic pelvic pain syndrome; chronic prostatitis; interstitial cystitis; symptom exacerbation.

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

Clemens JQ, Locke K Jr, Landis JR, Kreder K, Rodriguez LV, Yang CC, Tu FF, Harte SE, Schrepf A, Farrar JT, Sutcliffe S, Naliboff BD, Williams DA, Afari N, Spitznagle T, Taple BJ, Lai HH; Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.
Neurourol Urodyn. 2024 Mar;43(3):727-737. doi: 10.1002/nau.25400. Epub 2024 Jan 25. [PMID: 38270336] [PMC10981467]

Abstract

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: chronic prostatitis/chronic pelvic pain syndrome; interstitial cystitis/bladder pain syndrome; pelvic pain; prostate; urinary bladder.

Mapping Brain Structure Variability in Chronic Pain: The Role of Widespreadness and Pain Type and Its Mediating Relationship With Suicide Attempt.

Bhatt RR, Haddad E, Zhu AH, Thompson PM, Gupta A, Mayer EA, Jahanshad N.
Biol Psychiatry. 2024 Mar 1;95(5):473-481. doi: 10.1016/j.biopsych.2023.07.016. Epub 2023 Aug 4. [PMID: 37543299] [PMC10838358]; Supported by: DK082370 (MAYER, E; RODRIGUEZ L)

Abstract

Abstract

Background: Chronic pain affects nearly 20% of the U.S.

Population: It is a leading cause of disability globally and is associated with a heightened risk for suicide. The role of the central nervous system in the perception and maintenance of chronic pain has recently been accepted, but specific brain circuitries involved have yet to be mapped across pain types in a large-scale study.

Methods: We used data from the UK Biobank (N = 21,968) to investigate brain structural alterations in individuals reporting chronic pain compared with pain-free control participants and their mediating effect on history of suicide attempt.

Results: Chronic pain and, more notably, chronic multisite pain was associated with, on average, lower surface area throughout the cortex after adjusting for demographic, clinical, and neuropsychiatric confounds. Only participants with abdominal pain showed lower subcortical volumes, including the amygdala and brainstem, and lower cerebellum volumes. Participants with chronic headaches showed a widespread thicker cortex compared with control participants. Mediation analyses revealed that precuneus thickness mediated the relationship of chronic multisite pain and history of suicide attempt. Mediating effects were also identified specific to localized pain, with the strongest effect being amygdala volume in individuals with chronic abdominal pain.

Conclusions: Results support a widespread effect of chronic pain on brain structure and distinct brain structures underlying chronic musculoskeletal pain, visceral pain, and headaches. Mediation effects of regions in the extended ventromedial prefrontal cortex subsystem suggest that exacerbated negative internal states, negative self-referencing, and impairments in future planning may underlie suicidal behaviors in individuals with chronic pain.

Keywords: Big data; Biobank; Chronic pain; MRI; Neuroimaging; Suicide.

Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural correlates of perceived and relative resilience in male and female patients with irritable bowel syndrome.

Kilpatrick LA, Gupta A, Tillisch K, Labus JS, Naliboff BD, Mayer EA, Chang L.
Neurogastroenterol Motil. 2024 Feb;36(2):e14710. doi: 10.1111/nmo.14710. Epub 2023 Nov 29. [PMID: 38031358] [PMC11014739]; Supported by: DK082370 (MAYER, E; RODRIGUEZ L)

Abstract

Abstract

Background: Patients with irritable bowel syndrome (IBS) show lower resilience than healthy controls (HCs), associated with greater symptom severity and worse quality of life. However, little is known about affected markers of resilience or the influence of sex. Furthermore, as resilience is complex, a comprehensive assessment, with multiple resilience measures, is needed. Therefore, we aimed to evaluate perceived and relative resilience and their neural correlates in men and women with IBS.

Methods: In 402 individuals (232 IBS [73.3% women] and 170 HCs [61.2% women]), perceived resilience was assessed by the Connor-Davidson Resilience Scale (CDRISC) and Brief Resilience Scale (BRS); relative resilience was assessed by the standardized residual of the Short Form-12 mental component summary score predicted by the Adverse Childhood Experiences score. Non-rotated partial least squares analysis of region-to-region resting-state connectivity data was used to define resilience-related signatures in HCs. Disease and sex-related differences within these signatures were investigated.

Key results: Scores on all resilience measures were lower in IBS than in HCs (p's < 0.05). In all three resilience-related signatures, patients with IBS showed reduced connectivity largely involving the central autonomic network (p's < 0.001). Men with IBS showed lower CDRISC scores than women with IBS, and greater reductions in CDRISC-related connectivity, associated with worse symptom severity (p < 0.05).

Conclusions and inferences: Individuals with IBS show reduced perceived and relative resilience, with reduced connectivity suggesting impaired homeostasis maintenance. Men with IBS may show additional impairment in specific aspects of resilience. Treatments aimed at improving resilience may benefit patients with IBS, especially men with IBS.

Keywords: functional magnetic resonance imaging; irritable bowel syndrome; psychological resilience; sex differences.

© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Believing Women: A Qualitative Exploration of Provider Disbelief and Pain Dismissal among Women with Interstitial Cystitis/Bladder Pain Syndrome from the MAPP Research Network

Brown VL, James A, Hunleth J, Bradley CS, Farrar JT, Gupta P, Lai HH, Lowder JL, Moldwin R, Rodriguez LV, Yang CC, Sutcliffe S.
Int Urogynecol J. 2024 Jan;35(1):139-148. doi: 10.1007/s00192-023-05677-0. Epub 2023 Nov 22. [PMID: 37991567] [PMC11019919]

Abstract

Abstract

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.

Keywords: Chronic pain; Delayed diagnosis; Interstitial cystitis; Patient–provider encounter; Qualitative; Women.

© 2023. The International Urogynecological Association.

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

Martucci KT, Karshikoff B, Mackey SC.
Physiol Behav. 2023 Nov 1;271:114358. doi: 10.1016/j.physbeh.2023.114358. Epub 2023 Sep 26. [PMID: 37769862] [PMC10599305]

Abstract

Abstract

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.

Keywords: Amygdala; Cytokine; Hippocampus; IL-6; Inflammation; fMRI.

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.

Schrepf AD, Mawla I, Naliboff BD, Gallop B, Moldwin RM, Tu F, Gupta P, Harte S, Krieger JN, Yang C, Bradley C, Rodriguez L, Williams D, Magnotta V, Ichesco E, Harris RE, Clemens Q, Mullins C, Kutch JJ.
Pain. 2023 Oct 1;164(10):2343-2351. doi: 10.1097/j.pain.0000000000002944. Epub 2023 Jun 6.  [PMID: 37278657] [PMC10524087]

Abstract

Abstract

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.

Keywords: Chronic pain, Bladder, Urology, Resting-state, fMRI, Flare-up, Healthcare utilization.

Trial registration: ClinicalTrials.gov NCT02514265.

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.

Pierce J, Harte SE, Afari N, Bradley CS, Griffith JW, Kim J, Lutgendorf S, Naliboff BD, Rodriguez LV, Taple BJ, Williams D, Harris RE, Schrepf A; MAPP Research Network.
Pain. 2023 Sep 1;164(9):1995-2008. doi: 10.1097/j.pain.0000000000002895. Epub 2023 May 5. [PMID: 37144687] [PMC10440258]

Abstract

Abstract

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.

Keywords: Trauma, Childhood abuse, Pain sensitivity, Quantitative sensory testing.

Copyright © 2023 International Association for the Study of Pain.

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia.

Lim M, Kim DJ, Nascimento TD, Ichesco E, Kaplan C, Harris RE, DaSilva AF.
Neuromodulation. 2023 Jul;26(5):999-1008. doi: 10.1111/ner.13512. Epub 2022 Jun 14. [PMID: 34309138] [PMC8789944].

Abstract

Abstract

Objectives: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement.

Materials and methods: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SDBOLD), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SDBOLD was compared to 15 healthy female controls.

Results: At baseline, FM patients showed reduced SDBOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SDBOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SDBOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SDBOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SDBOLD in the rACC/vmPFC but with a decreased SDBOLD in the posterior insula.

Conclusion: Our findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM.

Keywords: Brain signal variability; brain stimulation; fibromyalgia; resting-state fMRI; tDCS

Copyright © 2022. Published by Elsevier Inc.

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.

Lutgendorf SK, Zia S, Luo Y, O’Donnell M, van Bokhoven A, Bradley CS, Gallup R, Pierce J, Taple BJ, Naliboff BD, Quentin Clemens J, Kreder KJ, Schrepf A.
Brain Behav Immun. 2023 Jul;111:116-123. doi: 10.1016/j.bbi.2023.03.024. Epub 2023 Mar 29. [PMID: 37001828] [PMC10474614]

Abstract

Abstract

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-1β, 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

Keywords: Chronic stress; Cortisol; Early life adversity; HPA axis; IC/BPS; Inflammation; Interstitial cystitis; Pain; Recent life adversity.

Copyright © 2023 Elsevier Inc. All rights reserved.

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

Stephens-Shields AJ, Lai HH, Landis JR, Kreder K, Rodriguez LV, Naliboff BD, Afari N, Sutcliffe S, Moldwin R, Griffith JW, Clemens JQ, Bradley CS, Quallich S, Gupta P, Harte SE, Farrar JT.
J Urol. 2023 Jun;209(6):1132-1140. doi: 10.1097/JU.0000000000003394. Epub 2023 Feb 27. [PMID: 36848118] [PMC11062515]

Abstract

Abstract

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.

Keywords: cystitis, interstitial; minimal clinically important difference; pelvic pain; research design; treatment outcome.

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.

Sutcliffe S, Newcomb C, Bradley CS, Clemens JQ, Erickson B, Gupta P, Lai HH, Naliboff B, Strachan E, Stephens-Shields A.
J Urol. 2023 Apr 1;209(4):719-725. doi: 10.1097/JU.0000000000003155. Epub 2023 Jan 11. [PMID: 36630590] [PMC10333444]

Abstract

Abstract

Purpose: 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).

Materials and methods: 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.

Results: 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).

Conclusions: 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.

Keywords: cystitis, interstitial; prostatitis; symptom flare up.

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.

Wang C, Kutch JJ, Labus JS, Yang CC, Harris RE, Mayer EA, Ellingson BM.
J Pain. 2023 Apr;24(4):627-642. doi: 10.1016/j.jpain.2022.11.008. Epub 2022 Nov 23. [PMID: 36435486] [PMC10676766]

Abstract

Abstract

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. PERSPECTIVE: This 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.

Keywords: Urological chronic pelvic pain; UCPPS; Longitudinal observation; Diffusion tensor imaging; Probabilistic tractography.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/ Bladder Pain Syndrome: A MAPP Network Study.

Farrar JT, Locke KT Jr., Clemens JQ, Griffith JW, Harte SE, Kirkali Z, Kreder KJ, Krieger JN, Lai HH, Moldwin RM, Mullins C, Naliboff BD, Pontari MA, Rodriguez LV, Schaeffer AJ, Schrepf A, Stephens-Shields A, Sutcliffe S, Taple BJ, Williams DA, Landis JR.
Res Sq. 2023 Feb 23;rs.3.rs-2441086. doi: 10.21203/rs.3.rs-2441086/v1. Preprint [PMID: 36865104] [PMC9980200]

Abstract

Abstract

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested in clinical trials. Using data from three previously published negative studies of the treatment of interstitial cystitis/ bladder pain with data on the extent of widespread pain, we examined the response of patients to different therapies base on the amount of pain beyond the pelvis. Participants with predominately local but not widespread pain responded to therapy targeting local symptoms. Participants with widespread and local pain responded to therapy targeting widespread pain. Differentiating patients with and without widespread pain phenotypes may be a key feature of designing future pain clinical trials to demonstrate treatments that are effective versus not.

Keywords: Randomized controlled trials; Chronic pain; Epidemiology; Functional clustering.

This is a preprint. It has not yet been peer reviewed by a journal. The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

2022

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

Loh-Doyle JC, Stephens-Shields AJ, Rolston R, Newcomb C, Taple B, Sutcliffe S, Yang CC, Lai H, Rodriguez LV.
J Sex Med. 2022 Dec;19(12):1804-1812. doi: 10.1016/j.jsxm.2022.08.196. Epub 2022 Sep 28. [PMID: 36180370] [PMC10916540]

Abstract

Abstract

Background: Sexual 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)).

Aim: We 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.

Methods: Baseline 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.

Outcomes: Comorbidities, 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.

Results: There 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 implications: A multidisciplinary approach that addresses the identified risk factors for SD may improve overall QoL in males with UCPPS.

Strengths and limitations: Our 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.

Conclusions: When 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.

Keywords: Chronic Pelvic Pain; Chronic Prostatitis; Ejaculatory Dysfunction; Erectile Dysfunction; Sexual Dysfunction.

Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

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

Bradley CS , Gallop R , Sutcliffe S, Kreder KJ, Lai HH, Clemens JQ, Naliboff BD, for the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.
Urology. 2022 Nov;169:58-64. doi: 10.1016/j.urology.2022.07.045. Epub 2022 Aug 9. [PMID: 35961564] [PMC10590538]

Abstract

Abstract

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.

Keywords: Chronic prostatitis; extended follow-up; interstitial cystitis; MAPP network cohort study; urologic chronic pelvic pain syndrome; bladder pain syndrome.

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

Schrepf A, Gallop R, Naliboff B, Harte SE, Afari N, Lai HH, Pontari M, McKernan LC, Strachan E, Kreder KJ, As-Sanie SA, Rodriguez LV, Griffith JW, Williams DA; Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.
J Pain. 2022 Sep;23(9):1594-1603. doi: 10.1016/j.jpain.2022.03.240. Epub 2022 Apr 25. [PMID: 35472518] [PMC10547025]

Abstract

Abstract

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.

Keywords: Nociceptive pain; central nervous system sensitization; chronic pain; cystitis; neuropathic pain.

The healthy urinary microbiome in asymptomatic participants in the MAPP Network Study: Relation to gender, age, and menopausal status.

Nickel JC, Stephens A, Ackerman AL, Anger JT, Lai HH, Ehrlich GD.
Can Urol Assoc J. 2022 Sep;16(9):E448-E454. doi: 10.5489/cuaj.7775. [PMID: 35426787] [PMC9484748]

Abstract

Abstract

Introduction: To understand the role of the urinary microbiome in disease states and interpret non-culture-based diagnostic urine testing of midstream urine specimens, we must have a better understanding of the urinary microbiome in asymptomatic, healthy individuals. We examined the impact of gender, age, and menopausal status on the healthy human urinary microbiome in asymptomatic control subjects enrolled in the multi-institution National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network (MAPP) study.

Methods: Asymptomatic, healthy controls, recruited to be ageand sex-matched to patients in the Trans-MAPP Epidemiology and Phenotyping Study, provided midstream urine collection for polymerase chain reaction (PCR)-electrospray ionization mass spectrometry identification of urinary microbiota. The microbiomes of male and female participants were described and analyzed for differences in composition and diversity at the species and genus level by sex, age, and, in females, by menopausal status.

Results: Sixty-six total species were detected with a mean of 1.2 species (standard deviation [SD] 1.1) per male (n=97; mean age=43) and 2.3 (SD 1.3) per female (n=110, mean age=38) in asymptomatic, healthy controls. Species and genera diversity analyses showed significantly greater richness and diversity in females. With regard to species, Bifidobacterium subtile, Lactobacillus crispatus, and Lactobacillus johnsonii were more predominant in females. The genera Bifidobacterium, Staphylococcus, Lactobacillus, and Corynebacterium were more predominant in females, while for males the most prevalent organisms included Staphylococcus and Propionibacterium; only Propionibacterium approached a significant difference between genders. No significant difference in the presence and/or diversity of micro-organisms with menopausal status could be observed. Sex-specific age trends, particularly diversity, were larger for females than males.

Conclusions: These results suggest the urinary microbiome of healthy, asymptomatic subjects differed between genders and age in females, but not menopausal status. Gender differences may be attributable to the detection of urethral/vaginal organisms in females and prostate organisms in males. These findings will better allow us to interpret the results of microbiome reports in the midstream urine specimens of patients with urinary symptoms.

Keywords: Microbiome; Urinary; Urinary Tract Infection; Age; Gender.

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.

Gupta P, Gallop R, Spitznagle T, Lai H, Tu F, Krieger JN, Clemens JQ, Bradley CS, Yang C, Sutcliffe S, Moldwin R, Kreder K, Kutch J, Rodriguez LV.
J Urol. 2022 Aug;208(2):341-349. doi: 10.1097/JU.0000000000002679. Epub 2022 Mar 28. [PMID: 35344391] [PMC10123541]

Abstract

Abstract

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.

Keywords: chronic prostatitis with chronic pelvic pain syndrome; cystitis; interstitial; pelvic pain.

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.

Quallich SA, Quentin Clemens J, Ronstrom C, James AS, Kreder KJ, Henry Lai H, Naliboff BD, Rodriguez LV, Berry SH, Sutcliffe S.
Neurourol Urodyn. 2022 Aug;41(6):1468-1481. doi: 10.1002/nau.24983. Epub 2022 Jun 10. [PMID: 35686553] [PMC11033701]

Abstract

Abstract

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.

Keywords: chronic prostatitis; diet; focus group; pelvic pain; prostatitis; quality of life; symptom exacerbation; urinary bladder.

Reliability and validity of pain and urinary symptom severity assessment in urologic chronic pelvic pain; A MAPP Network Analysis.

Naliboff BD, Locke K Jr, Schrepf D, Griffith JW, Moldwin R, Krieger JN, Rodriguez LV, Stephens-Shields AJ, Clemens JQ, Lai HH, Sutcliffe S, Taple BJ, Williams D, Pontari MA, Mullins C, Landis JR; MAPP Research Network.
J Urol. 2022 Jun;207(6):1246-1255. doi: 10.1097/JU.0000000000002438. Epub 2022 Jan 21. [PMID: 35060778] [PMC10494963]

Abstract

Abstract

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.

Keywords: cystitis, interstitial; lower urinary tract symptoms; pelvic pain; prostatitis.

Functional Mixed Effects Clustering with Application to Longitudinal Urologic Chronic Pelvic Pain Syndrome Symptom Data.

Guo, WS; You, MY; Yi, JL; Pontari, MA; Landis, JR.
J Am Stat Assoc. 2022;117(540):1631-1641. doi: 10.1080/01621459.2022.2066536. Epub 2022 May 13. [PMID: 36845296] [PMC9949755]

Abstract

Abstract

By clustering patients with the urologic chronic pelvic pain syndromes (UCPPS) into homogeneous subgroups and associating these subgroups with baseline covariates and other clinical outcomes, we provide opportunities to investigate different potential elements of pathogenesis, which may also guide us in selection of appropriate therapeutic targets. Motivated by the longitudinal urologic symptom data with extensive subject heterogeneity and differential variability of trajectories, we propose a functional clustering procedure where each subgroup is modeled by a functional mixed effects model, and the posterior probability is used to iteratively classify each subject into different subgroups. The classification takes into account both group-average trajectories and between-subject variabilities. We develop an equivalent state-space model for efficient computation. We also propose a cross-validation based Kullback-Leibler information criterion to choose the optimal number of subgroups. The performance of the proposed method is assessed through a simulation study. We apply our methods to longitudinal bi-weekly measures of a primary urological urinary symptoms score from a UCPPS longitudinal cohort study, and identify four subgroups ranging from moderate decline, mild decline, stable and mild increasing. The resulting clusters are also associated with the one-year changes in several clinically important outcomes, and are also related to several clinically relevant baseline predictors, such as sleep disturbance score, physical quality of life and painful urgency.

Keywords: Functional clustering; Kullback-Leibler information criterion; Smoothing Spline; State Space model.

Longitudinal Changes in the Pelvic Pain Only and Widespread Pain Phenotypes Over One Year in the MAPP-I Urologic Chronic Pelvic Pain Syndrome (UCPPS) Cohort.

Lai H, Bayman EO, Bishop MO, Landis R, Harte SE, Clemens Q, Rodriguez LV, Sutcliffe S, Taple BJ, Naliboff BD; MAPP Research Network.
Urology. 2022 Mar;161:31-35. doi: 10.1016/j.urology.2021.12.016. Epub 2022 Jan 10. [PMID: 35021046] [PMC9502024]

Abstract


Abstract

Objective: To examine how often urologic chronic pelvic pain syndrome (UCPPS) patients progressed from Pelvic Pain Only at baseline to Widespread Pain, or vice versa, during 1-year longitudinal follow-up.

Methods: Men and women with UCPPS enrolled in the MAPP-I Epidemiology and Phenotyping Study completed a self-report body map to indicate their locations of pain every 2 months over 12 months. Patients were categorized at each assessment into one of three pain phenotypes: (1) Pelvic Pain Only, (2) an Intermediate group, (3) Widespread Pain. Only patients who completed 3 or more follow-ups were included in this longitudinal analysis. The primary outcome measure was pain classification at the majority (≥60%) of follow-up assessments. Longitudinal trends of somatic symptom burden were also assessed.

Results: Among the 93 UCPPS participants with Pelvic Pain Only at baseline, only 2% (n = 2) showed a Widespread Pain phenotype for the majority of assessments over 12 months. Among the 121 participants who had Widespread Pain at baseline, 6% (n = 7) demonstrated Pelvic Pain Only for the majority of assessments over 12 months. Over half of participants (≥53%) stayed in their baseline phenotypic group. Somatic symptom burden remained stable over 12 months for each of the groups with high intra-class correlation coefficient (0.67 to 0.82).

Conclusion: It was uncommon for UCPPS patients to progress from Pelvic Pain Only to Widespread Pain, or vice versa, over 12 months. These data suggest that Pelvic Pain Only and Widespread Pain are distinct UCPPS phenotypes that are relatively stable over 12 months of follow up.

Keywords: Complex Multiple Symptoms Inventory; chronic prostatitis/chronic pelvic pain syndrome; interstitial cystitis/bladder pain syndrome; Intra-class coefficient; intermediate pain; pelvic pain only; urologic chronic pelvic pain syndrome; widespread pain.

The urinary proteomic profile implicates key regulators for urologic chronic pelvic pain syndrome (UCPPS): A MAPP Research Network Study.

Froehlich JW, Scott Wang HH, Logvinenko T, Kostel S, DiMartino S, van Bokhoven A, Moses MA, Lee RS; MAPP Research Network.
Mol Cell Proteomics. 2022 Jan;21(1):100176. doi: 10.1016/j.mcpro.2021.100176. Epub 2021 Nov 11. [PMID: 34774759] [PMC8733275]

Abstract

Abstract

Urologic chronic pelvic pain syndrome (UCPPS) is a condition of unknown etiology characterized by pelvic pain and urinary frequency and/or urgency. As the proximal fluid of this syndrome, urine is an ideal candidate sample matrix for an unbiased study of UCPPS. In this study, a large, discovery-phase, TMT-based quantitative urinary proteomics analysis of 244 participants was performed. The participants included patients with UCPPS (n = 82), healthy controls (HC) (n = 94), and disparate chronic pain diseases, termed positive controls (PC) (n = 68). Using training and testing cohorts, we identified and validated a small and distinct set of proteins that distinguished UCPPS from HC (n = 9) and UCPPS from PC (n = 3). The validated UCPPS: HC proteins were predominantly extracellular matrix/extracellular matrix modifying or immunomodulatory/host defense in nature. Significantly varying proteins in the UCPPS: HC comparison were overrepresented by the members of several dysregulated biological processes including decreased immune cell migration, decreased development of epithelial tissue, and increased bleeding. Comparison with the PC cohort enabled the evaluation of UCPPS-specific upstream regulators, contrasting UCPPS with other conditions that cause chronic pain. Specific to UCPPS were alterations in the predicted signaling of several upstream regulators, including alpha-catenin, interleukin-6, epidermal growth factor, and transforming growth factor beta 1, among others. These findings advance our knowledge of the etiology of UCPPS and inform potential future clinical translation into a diagnostic panel for UCPPS.

Keywords: TMT; UCPPS; bladder; inflammation; urine.

2021

Cerebral Perfusion and Sensory Testing Results Differ in Interstitial Cystitis/Bladder Pain Syndrome Patients with and without Fibromyalgia: A Site-Specific MAPP Network Study.

Deutsch G, Deshpande H, Lai HH, Kutch JJ, Ness TJ.
 J Pain Res. 2021 Dec 23;14:3887-3895. doi: 10.2147/JPR.S343695. eCollection 2021.  [PMID: 34992450] [PMC8711634]

Abstract

Abstract

Purpose: Fibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity.

Patients and methods: Female subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis of fibromyalgia as well as healthy control subjects (n = 41) underwent quantitative sensory testing. A subset of these patients (9 with and 9 without fibromyalgia) underwent brain perfusion studies using arterial spin labeled functional magnetic resonance imaging. An analysis was performed of absolute regional cerebral blood flow of regions-of-interest when experiencing a full bladder compared with an empty bladder.

Results: Subjects with both interstitial cystitis and fibromyalgia were more hypersensitive than those without fibromyalgia as well as healthy controls in most sensory measures except heat. Subjects with interstitial cystitis, but no fibromyalgia, differed from healthy controls only in toleration of the ischemic forearm task. Other co-morbidities were more common in those subjects with both interstitial cystitis and fibromyalgia. Bladder fullness was associated with significantly greater whole brain gray matter blood flow in subjects with interstitial cystitis and fibromyalgia when compared with that of subjects with interstitial cystitis without fibromyalgia. Examination of regional cerebral blood flow in individual regions-of-interest demonstrated statistically significant differences between the subjects with interstitial cystitis with and those without fibromyalgia bilaterally in the thalamus, amygdala and hippocampus, as well as the right prefrontal cortex and greater responsiveness to changes in bladder fullness in the insula.

Conclusion: Quantitative sensory testing and brain perfusion data support that there are two phenotypes of interstitial cystitis patients, which can be differentiated by a co-diagnosis of fibromyalgia. This may affect responsiveness to treatment and suggest the utility of stratifying interstitial cystitis patients according to their co-morbidities.

Keywords: QST; arterial spin labelling; fMRI; interstitial cystitis.

Anesthetic Bladder Capacity is a Clinical Biomarker for Interstitial Cystitis/Bladder Pain Syndrome Subtypes.

Plair A, Evans RJ, Langefeld CD, Matthews CA, Badlani G, Walker SJ.
Urology. 2021 Dec;158:74-80. doi: 10.1016/j.urology.2021.07.009. Epub 2021 Jul 22. [PMID: 34303757] [PMC8671173]

Abstract

Abstract

Objective: To further examine anesthetic bladder capacity as a biomarker for interstitial cystitis/bladder pain syndrome (IC/BPS) patient subtypes, we evaluated demographic and clinical characteristics in a large and heterogeneous female patient cohort.

Material and methods: This is a retrospective review of data from women (n = 257) diagnosed with IC/BPS who were undergoing therapeutic bladder hydrodistention (HOD). Assessments included medical history and physical examination, validated questionnaire scores, and anesthetic BC. Linear regression analyses were computed to model the relationship between anesthetic BC and patient demographic data, symptoms, and diagnoses. Variables exhibiting suggestive correlations (P ≤ .1) were candidates for a multiple linear regression analysis and were retained if significant (P ≤ .05).

Results: Multiple regression analysis identified a positive correlation between BC and endometriosis (P = .028) as well as negative correlations between BC and both ICSI score (P < .001) and the presence of Hunner's lesions (P < .001). There were higher average numbers of pelvic pain syndrome (PPS) diagnoses (P = .006) and neurologic, autoimmune, or systemic pain (NASP) diagnoses (P = .003) in IC/BPS patients with a non-low BC, but no statistical difference in the duration of diagnosis between patients with low and non-low BC (P = .118).

Conclusion: These data, generated from a large IC/BPS patient cohort, provide additional evidence that higher BC correlates with higher numbers of non-bladder-centric syndromes while lower BC correlates more closely with bladder-specific pathology. Taken together, the results support the concept of clinical subgroups in IC/BPS.

Keywords: interstitial cystitis/bladder pain syndrome, hydrodistention, anesthetic bladder capacity, biomarker; DK082316 (Stephens-Shields AJ; Landis JR)

Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement.

Jacobs JP, Gupta A, Bhatt RR, Brawer J, Gao K, Tillisch K, Lagishetty V, Firth R, Gudleski GD, Ellingson BM, Labus JS, Naliboff BD, Lackner JM, Mayer EA.
2021 Nov 30;9(1):236. doi: 10.1186/s40168-021-01188-6. [PMID: 34847963] [PMC8630837]

Abstract

Abstract

Background: There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis.

Methods: Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models.

Results: At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders.

Conclusions: Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT. Video abstract.

Keywords: Biomarkers; Brain-gut-microbiome axis; Cognitive behavioral therapy; Irritable bowel syndrome; Neuroimaging; Outcome prediction.

Urobiome: An outlook on the metagenome of urological diseases.

Shoemaker R, Kim J. Urobiome: An outlook on the metagenome of urological diseases. Investig Clin Urol. 2021 Nov;62(6):611-622. doi: 10.4111/icu.20210312. [PMID: 34729961] [PMC8566783]

Abstract

Abstract

The urinary tract likely plays a role in the development of various urinary diseases due to the recently recognized notion that urine is not sterile. In this mini review, we summarize the current literature regarding the urinary microbiome and mycobiome and its relationship to various urinary diseases. It has been recently discovered that the healthy urinary tract contains a host of microorganisms, creating a urinary microbiome. The relative abundance and type of bacteria varies, but generally, deviations in the standard microbiome are observed in individuals with urologic diseases, such as bladder cancer, benign prostatic hyperplasia, urgency urinary incontinence, overactive bladder syndrome, interstitial cystitis, bladder pain syndrome, and urinary tract infections. However, whether this change is causative, or correlative has yet to be determined. In summary, the urinary tract hosts a complex microbiome. Changes in this microbiome may be indicative of urologic diseases and can be tracked to predict, prevent, and treat them in individuals. However, current analytical and sampling collection methods may present limitations to the development in the understanding of the urinary microbiome and its relationship with various urinary diseases. Further research on the differences between healthy and diseased microbiomes, the long-term effects of antibiotic treatments on the urobiome, and the effect of the urinary mycobiome on general health will be important in developing a comprehensive understanding of the urinary microbiome and its relationship to the human body.

Keywords: Microbiome; Mycobiome; Urology; DK103260 (ANGER, J; FREEMAN, M)

Stress-Induced Accumulation of HnRNP K into Stress Granules.

Kim J, Yeon A, Kim WK, Kim KH, Ohn T.
J Cancer Sci Clin Ther. 2021;5(4):434-447. doi: 10.26502/jcsct.5079129. Epub 2021 Oct 15. [PMID: 35340804] [PMC8955021]

Abstract

Abstract

Stress granules (SGs) are cytoplasmic aggregates to reprogram gene expression in response to cellular stimulus. Here, we show that while SGs are being assembled in response to clotrimazole, an antifungal medication heterogeneous nuclear ribonucleoprotein (hnRNP) K, an RNA-binding protein that mediates translational silencing of mRNAs, is rapidly accumulated in SGs in U-2OS osteosarcoma cells. Forced expression of hnRNP K induces resistance to clotrimazole-induced apoptosis. Erk/MAPK is transiently activated in response to clotrimazole, and pharmacological suppression of the Erk/MAPK pathway sensitizes the cells to apoptosis. Inhibition of the Erk/MAPK pathway promotes the assembly of SGs. These results suggest that dynamic cytoplasmic formation of SGs and hnRNP K relocation to SGs may be defensive mechanisms against clotrimazole-induced apoptosis in U-2OS osteosarcoma cells.

Keywords: Apoptosis; Erk/MAPK; Stress granules; hnRNPK; DK103260 (ANGER, J; FREEMAN, M)

Relationship Between Blood Cytokine Levels, Psychological Comorbidity, and Widespreadness of Pain in Chronic Pelvic Pain.

Karshikoff B, Martucci KT, Mackey S.
Front Psychiatry. 2021 Jun 25;12:651083. doi: 10.3389/fpsyt.2021.651083. eCollection 2021. [PMID: 34248700] [PMC8267576]

Abstract

Abstract

Background: Low-grade inflammation has been implicated in the etiology of depression, long-term fatigue and chronic pain. TNFα and IL-6 are perhaps the most studied pro-inflammatory cytokines in the field of psychoneuroimmunology. The purpose of our study was to further investigate these relationships in patients with chronic pelvic pain specifically. Using plasma samples from a large, well-described cohort of patients with pelvic pain and healthy controls via the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, we examined the relationship between TNFα and IL-6 and comorbid psychological symptoms. We also investigated the relationship between IL-8 and GM-CSF, and widespreadness of pain. 

Methods: We included baseline blood samples in the analyses, 261 patients (148 women) and 110 healthy controls (74 women). Fourteen pro- and anti-inflammatory or regulatory cytokines were analyzed in a Luminex® xMAP® high-sensitivity assay. We used regression models that accounted for known factors associated with the outcome variables to determine the relationship between cytokine levels and clinical measures. 

Results: There were no statistical differences in cytokine levels between patients and healthy controls when controlling for age. In patients, TNFα was significantly associated with levels of fatigue (p = 0.026), but not with pain intensity or depression. IL-6 was not significantly related to any of the outcome variables. Women with pelvic pain showed a negative relationship between IL-8 and widespreadness of pain, while men did not (p = 0.003). For both sexes, GM-CSF was positively related to widespreadness of pain (p = 0.039). 

Conclusion: Our results do not suggest low-grade systemic inflammation in chronic pelvic pain. Higher TNFα blood levels were related to higher fatigue ratings, while higher systemic GM-CSF levels predicted more widespread pain. Our study further suggests a potentially protective role of IL-8 with regard to with regard to the widepreadness of pain in the body, at least for women.

Keywords: chronic pain; comorbidity; cytokine-immunological terms; inflammation; pelvic pain; DK082316 (Stephens-Shields AJ; Landis JR).

Temporal relationships between pain, mood and urinary symptoms in urological chronic pelvic pain syndrome: A MAPP Network Study.

Naliboff BD, Schrepf AD, Stephens-Shields AJ, Clemens JQ, Pontari MA, Labus J, Taple BJ, Rodriguez LV, Strachan E, Griffith JW.
J Urol. 2021 Jun;205(6):1698-1703. doi: 10.1097/JU.0000000000001595. Epub 2021 Feb 4. [PMID: 33535797] [PMC9179931]

Abstract

Abstract

Purpose: We sought to determine the time-lagged, bidirectional relationships among clinical variables of pelvic pain, urinary symptoms, negative mood, nonpelvic pain and quality of life in men and women with urological chronic pelvic pain syndrome, incorporating interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome.

Materials and methods: A total of 204 female and 166 male patients were assessed up to 24 times over a 48-week period on the 5 primary outcomes. A lagged autoregressive analysis was applied to determine the directional relationship of one variable to another 2 weeks later, beyond that of the concurrent relationships at each time point and autocorrelations and trends over time.

Results: The results show clear evidence for a bidirectional positive relationship between changes in pelvic pain severity and urinary symptom severity. Increases in either variable predicted significant increases in the other 2 weeks later, beyond that explained by their concurrent relationship at each time point. Pelvic pain and to a lesser degree urinary frequency also showed similar bidirectional relationships with negative mood and decreased quality of life. Interestingly, neither pelvic pain or urinary symptom severity showed lagged relationships with nonpelvic pain severity.

Conclusions: Results document for the first time specific short-term positive feedback between pelvic pain and urinary symptoms, and between symptoms of urological chronic pelvic pain syndrome, mood and quality of life. The feedforward aspects of these relationships can facilitate a downward spiral of increased symptoms and worsening psychosocial function, and suggest the need for multifaceted treatments and assessment to address this possibility in individual patients.

Trial registration: ClinicalTrials.gov NCT02514265.

Keywords: cystitis, interstitial; lower urinary tract symptoms; pain; pelvic pain; prostatitis.

Does pollen trigger urological chronic pelvic pain syndrome flares? a case-crossover analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

Javed I, Yu T, Li J, Pakpahan R, Milbrandt M, Andriole GL, Lowder JL, Lai HH, Colditz GA, Sutcliffe S.
J Urol. 2021 Apr;205(4):1133-1138. doi: 10.1097/JU.0000000000001482. Epub 2020 Dec 21. [PMID: 33347771] [PMC9075343]

Abstract

Abstract

Purpose: We sought to determine whether pollen triggers urological chronic pelvic pain syndrome flares.

Materials and methods: We assessed flare status every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain case-crossover analysis of flare triggers (NCT01098279). Flare symptoms, flare start date and exposures in the 3 days before a flare were queried for the first 3 flares and at 3 randomly selected nonflare times. These data were linked to daily pollen count by date and the first 3 digits of participants' zip codes. Pollen count in the 3 days before and day of a flare, as well as pollen rises past established thresholds, were compared to nonflare values by conditional logistic regression. Poisson regression was used to estimate flare rates in the 3 weeks following pollen rises past established thresholds in the full longitudinal study. Analyses were performed in all participants and separately in those who reported allergies or respiratory tract disorders.

Results: Although no associations were observed for daily pollen count and flare onset, positive associations were observed for pollen count rises past medium or higher thresholds in participants with allergies or respiratory tract disorders in the case-crossover (OR 1.31, 95% CI 1.04-1.66) and full longitudinal (RR 1.23, 95% CI 1.03-1.46) samples.

Conclusions: We found some evidence to suggest that rising pollen count may trigger flares of urological chronic pelvic pain syndrome. If confirmed in future studies, these findings may help to inform flare pathophysiology, prevention and treatment, and control over the unpredictability of flares.

Keywords: cystitis, interstitial; pelvic pain; pollen; prostatitis; symptom flare up.

Comparison of deep phenotyping features of UCPPS with and without Hunner lesion: A MAPP-II Research Network Study.

Lai HH, Newcomb C, Harte S, Appleby D, Ackerman AL, Anger JT, Nickel JC, Gupta P, Rodriguez LV, Landis JR, Clemens JQ; MAPP Research Network.
Neurourol Urodyn. 2021 Mar;40(3):810-818. doi: 10.1002/nau.24623. Epub 2021 Feb 19. [PMID: 33604963] [PMC8159180]

Abstract

Abstract

Objective: To use the phenotyping data from the MAPP-II Symptom Patterns Study (SPS) to compare the systemic features between urologic chronic pelvic pain syndrome (UCPPS) with Hunner lesion (HL) versus those without HL.

Methods: We performed chart review on 385 women and 193 men with UCPPS who enrolled in the MAPP-II SPS. 223 had cystoscopy and documentation of HL status. Among them, 12.5% had HL and 87.5% did not.

Results: UCPPS participants with HL were older, had increased nocturia, higher Interstitial Cystitis Symptom and Problem Indexes, and were more likely to report "painful urgency" compared with those without HL. On the other hand, UCPPS without HL reported more intense nonurologic pain, greater distribution of pain outside the pelvis, greater numbers of comorbid chronic overlapping pain conditions, higher fibromyalgia-like symptoms, and greater pain centralization, and were more likely to have migraine headache than those with HL. UCPPS without HL also had higher anxiety, perceived stress, and pain catastrophizing than those with HL. There were no differences in sex distribution, UCPPS symptom duration, intensity of urologic pain, distribution of genital pain, pelvic floor tenderness on pelvic examination, quality of life, depression, pain characteristics (nociceptive pain vs. neuropathic pain), mechanical hypersensitivity in the suprapubic area during quantitative sensory testing, and 3-year longitudinal pain outcome and urinary outcome between the two groups.

Conclusions: UCPPS with HL displayed more bladder-centric symptom profiles, while UCPPS without HL displayed symptoms suggesting a more systemic pain syndrome. The MAPP-II SPS phenotyping data showed that Hunner lesion is a distinct phenotype from non-Hunner lesion.

Keywords: Hunner lesion; chronic prostatitis; clinical phenotyping; interstitial cystitis; personalized medicine; ulcerative interstitial cystitis.

© 2021 Wiley Periodicals LLC.

A Mobile Phone Application for Assessing Daily Variation in Pain Location and Pain Intensity in Patients with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study.

Erickson BA, Herman T, Hahn AE, Taple BJ, Bass M, Lloyd RB, Sutcliffe S, Griffith JW.
Urol Pract. 2021 Mar;8(2):189-195. doi: 10.1097/UPJ.0000000000000203. Epub 2020 Oct 14. [PMID: 36419906] [PMC9662822]

Abstract

Abstract

Introduction: We created and tested a mobile app that facilitates the ecological momentary assessment of pain intensity and pain location and identifies heterogeneous patient pain phenotypes.

Methods: A mobile app was created with patient, clinician and researcher input. A sample of 20 participants with urologic chronic pelvic pain syndrome were then asked to complete a 14-day pain assessment using the app. Data were analyzed to assess compliance, usability and the ability for the app to capture variation in pain intensity and pain location. Ecological momentary assessment pain data were then compared to end-of-week pain summary questions to determine construct validity.

Results: Mean compliance was 70±8%, higher earlier in the study period (p <0.0005) and better in older individuals (p <0.0001). During the 14-day assessment, 90% of participants reported daily variation in pelvic pain intensity (SD 0.64-3.02; out of 10), 95% reported variation in their nonpelvic pain (SD 0.17-3.63; out of 10) and 100% reported variations in number of sites with pain (SD 0.22-1.44; out of 7). Pelvic pain and nonpelvic pain intensity, as determined by cumulative app scores, were associated with patient reported end-of-week scores; worst pain (r pelvic =0.67; r nonpelvic =0.53) and average pain (r pelvic =0.78; r nonpelvic =0.73).

Conclusions: The easy-to-use app captured unique patterns of pain not fully captured by traditional end-of-day/week summary questions or by traditional in-office assessments. Mobile apps for assessing chronic conditions will become increasingly important as telehealth becomes more commonplace.

Keywords: data collection; ecological momentary assessment; mobile applications; prostatitis.

Association of longitudinal changes in symptoms and urinary biomarkers in patients with urological chronic pelvic pain syndrome: A MAPP Research Network Study.

Roy R, Stephens AJ, Daisy C, Merritt L, Newcomb CW, Yang J, Dagher A, Curatolo A, Sachdev M, McNeish B, Landis R, van Bokhoven A, El-Hayek A, Froehlich J, Pontari MA, Zurakowski D, Lee RS, Moses MA.
J Urol. 2021 Feb;205(2):514-523. doi: 10.1097/JU.0000000000001391. Epub 2020 Oct 7. [PMID: 33026902] [PMC8139408]

Abstract

Abstract

Purpose: We analyzed a series of novel noninvasive urinary biomarkers for their ability to objectively monitor the longitudinal clinical status of patients with urological chronic pelvic pain syndrome.

Materials and methods: Baseline, 6 and 12-month urine samples were collected (216) and used to quantify vascular endothelial growth factor, vascular endothelial growth factor (VEGF) receptor 1 (R1), neutrophil gelatinase associated lipocalin (NGAL), matrix metalloproteinase-2, matrix metalloproteinase (MMP)-9, and MMP-9/NGAL complex by enzyme-linked immunosorbent assays. Patient symptom changes were classified as improved, stable or worse using a functional clustering algorithm. Proportional odds models were used to evaluate the association between symptom change and urinary biomarkers.

Results: Across all sampled participants, longitudinal decreases in normalized VEGF concentration (pg/μg) were associated with pain severity improvement, and decreases in MMP-9, NGAL and VEGF-R1 concentration (pg/ml) as well as NGAL normalized concentration were associated with improved urinary symptoms. Longitudinal decreases in normalized VEGF-R1 were associated with pain improvement in patients with moderate widespreadness, no bladder symptoms and no painful filling. Lower baseline normalized VEGF-R1 concentration was associated with pain improvement in patients with pelvic pain only. Higher baseline MMP-9/NGAL levels were associated with pain and urinary improvement across all participants. Moreover, longitudinal increases in MMP-2 concentration was associated with improved pain in men and patients with painful filling.

Conclusions: Our results suggest these urinary biomarkers may be useful in monitoring urological chronic pelvic pain syndrome symptom changes with respect to both urinary severity and pain severity. With further testing, they may represent objective biological measures of urological chronic pelvic pain syndrome progression and/or resolution while also providing insight into the pathophysiology of urological chronic pelvic pain syndrome.

Keywords: lipocalin-2; matrix metalloproteinases; pelvic pain; vascular endothelial growth factor; vascular endothelial growth factor receptor.

2020

Beyond the pan-genome: current perspectives on the functional and practical outcomes of the distributed genome hypothesis.

Hammond JA, Gordon EA, Socarras KM, Chang Mell J, Ehrlich GD.
Biochem Soc Trans. 2020 Dec 18;48(6):2437-2455. doi: 10.1042/BST20190713. [PMID: 33245329] [PMC7752077]

Abstract

Abstract

The principle of monoclonality with regard to bacterial infections was considered immutable prior to 30 years ago. This view, espoused by Koch for acute infections, has proven inadequate regarding chronic infections as persistence requires multiple forms of heterogeneity among the bacterial population. This understanding of bacterial plurality emerged from a synthesis of what-were-then novel technologies in molecular biology and imaging science. These technologies demonstrated that bacteria have complex life cycles, polymicrobial ecologies, and evolve in situ via the horizontal exchange of genic characters. Thus, there is an ongoing generation of diversity during infection that results in far more highly complex microbial communities than previously envisioned. This perspective is based on the fundamental tenet that the bacteria within an infecting population display genotypic diversity, including gene possession differences, which result from horizontal gene transfer mechanisms including transformation, conjugation, and transduction. This understanding is embodied in the concepts of the supragenome/pan-genome and the distributed genome hypothesis (DGH). These paradigms have fostered multiple researches in diverse areas of bacterial ecology including host-bacterial interactions covering the gamut of symbiotic relationships including mutualism, commensalism, and parasitism. With regard to the human host, within each of these symbiotic relationships all bacterial species possess attributes that contribute to colonization and persistence; those species/strains that are pathogenic also encode traits for invasion and metastases. Herein we provide an update on our understanding of bacterial plurality and discuss potential applications in diagnostics, therapeutics, and vaccinology based on perspectives provided by the DGH with regard to the evolution of pathogenicity.

Keywords: bacterial pathogenesis; comparative genomics; pan-genome; DK082316 (Stephens-Shields AJ; Landis JR).

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

Mawla I, Schrepf A, Ichesco E, Harte SE, Klumpp DJ, Griffith JW, Strachan E, Yang CC, Lai H, Andriole G, Magnotta VA, Kreder K, Clauw DJ, Harris RE, Clemens JQ, Landis JR, Mullins C, Rodriguez LV, Mayer EA, Kutch JJ.
Sci Rep. 2020 Nov 16;10(1):19901. doi: 10.1038/s41598-020-76857-x. [PMID: 33199816] [PMC7669903]

Abstract

Abstract

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

Keywords: bladder; functional magnetic resonance imaging.

Correlates of 1-year change in quality of life in patients with urologic chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Clemens JQ, Stephens-Shields AJ, Newcomb C, Rodriguez LV, Lai HH, Bradley CS, Naliboff BD, Griffith JW, Taple BJ, Gupta P, Afari N, Harte SE, Strachan E, Guo W, Landis JR.
J Urol. 2020 Oct;204(4):754-759. doi: 10.1097/JU.0000000000001080. Epub 2020 Apr 15. [PMID: 32294397] [PMC7483873]

Abstract

Abstract

Purpose: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome.

Materials and methods: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change.

Results: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life.

Conclusions: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Keywords: cystitis; interstitial; prostatitis.

The Seminal Microbiome and Male Factor Infertility.

Osadchiy V, Mills JN, Mayer EA, Eleswarapu SV. The Seminal Microbiome and Male Factor Infertility. Curr Sex Health Rep. 2020 Sep;12(3):202-207. doi: 10.1007/s11930-020-00273-5. Epub 2020 Jul 17. [PMID: 33746642] [PMC7968069]
Keywords: Anaerococcus; Male Infertility; Next Generation Sequencing; Semen Microbiome; DK082370 (MAYER, E; RODRIGUEZ L)

AOAH remodels arachidonic acid-containing phospholipid pools in a model of interstitial cystitis pain: A MAPP Network study.

Yang W, Yaggie RE, Schaeffer AJ, Klumpp DJ. AOAH remodels arachidonic acid-containing phospholipid pools in a model of interstitial cystitis pain: A MAPP Network study. PLoS One. 2020 Sep 14;15(9):e0235384. doi: 10.1371/journal.pone.0235384. eCollection 2020. [PMID: 32925915] [PMC7489500]
Keywords: pain; phospholipids; spinal cord; allodynia; transferases; lipids; homeostasis; cell membranes.

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

Clemens JQ, Kutch JJ, Mayer EA, Naliboff BD, Rodriguez LV, Klumpp DJ, Schaeffer AJ, Kreder KJ, Clauw DJ, Harte SE, Schrepf AD, Williams DA, Andriole GL, Lai HH, Buchwald D, Lucia MS, van Bokhoven A, Mackey S, Moldwin RM, Pontari MA, Stephens-Shields AJ, Mullins C, Landis JR. The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS). Neurourol Urodyn. 2020 Aug;39(6):1803-1814. doi: 10.1002/nau.24423. Epub 2020 Jun 23. [PMID: 32578257] [PMC8025696]
Keywords: chronic; interstitial cystitis; plasma biomarkers; prostatitis; urine biomarkers; urological chronic pelvic pain syndromes.

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

Holschneider DP, Wang Z, Chang H, Zhang R, Gao Y, Guo Y, Mao J, Rodriguez LV. Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study. Neurourol Urodyn. 2020 Aug;39(6):1628-1643. doi: 10.1002/nau.24424. Epub 2020 Jun 23. [PMID: 32578247] [PMC7642011]
Keywords: animal model; brain mapping; glutamate; micturition; painful bladder syndrome/interstitial cystitis; water avoidance stress.

Analysis of viruses present in urine from patients with interstitial cystitis.

Robles MTS, Cantalupo PG, Duray AM, Freeland M, Murkowski M, van Bokhoven A, Stephens-Shields AJ, Pipas JM, Imperiale MJ. Analysis of viruses present in urine from patients with interstitial cystitis. Virus Genes. 2020 Aug;56(4):430-438. doi: 10.1007/s11262-020-01767-z. Epub 2020 May 23. [PMID: 32447589] [PMC7339973]
Keywords: Interstitial cystitis; NGS; PCR; Polyomavirus; Virus discovery.

Does weather trigger urologic chronic pelvic pain syndrome flares? A case-crossover analysis in the multidisciplinary approach to the study of the chronic pelvic pain research network.

Li J, Yu T, Javed I, Siddagunta C, Pakpahan R, Langston ME, Dennis LK, Kingfield DM, Moore DJ, Andriole GL, Lai HH, Colditz GA, Sutcliffe S; MAPP Research Network. Does weather trigger urologic chronic pelvic pain syndrome flares? A case-crossover analysis in the multidisciplinary approach to the study of the chronic pelvic pain research network. Neurourol Urodyn. 2020 Jun;39(5):1494-1504. doi: 10.1002/nau.24381. Epub 2020 May 4. [PMID: 32893408] [PMC7479643]
Keywords: bladder pain syndrome; chronic pelvic pain syndrome; chronic prostatitis; flare; interstitial cystitis; trigger.

Sensitivity of functional connectivity to periaqueductal gray localization, with implications for identifying disease-related changes in chronic visceral pain: A MAPP Research Network neuroimaging study.

Fenske SJ, Bierer D, Chelimsky G, Conant L, Ustine C, Yan K, Chelimsky T, Kutch JJ. Sensitivity of functional connectivity to periaqueductal gray localization, with implications for identifying disease-related changes in chronic visceral pain: A MAPP Research Network neuroimaging study. Neuroimage Clin. 2020;28:102443. doi: 10.1016/j.nicl.2020.102443. Epub 2020 Sep 20. [PMID: 33027702] [PMC7548991]
Keywords: Brain parcellation; Brainstem; PAG; Resting-state; UCPPS; fMRI.

Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

Holschneider DP, Wang Z, Guo Y, Sanford MT, Yeh J, Mao JJ, Zhang R, Rodriguez LV. Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. Physiol Behav. 2020 Mar 1;215:112796. doi: 10.1016/j.physbeh.2019.112796. Epub 2019 Dec 27. [PMID: 31884113] [PMC7269603]
Keywords: Bladder pain syndrome; Exercise; Functional brain mapping; Interstitial cystitis; Micturition circuit; Psychological stress.

Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress-induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

Sanford MT, Yeh JC, Mao JJ, Guo Y, Wang Z, Zhang R, Holschneider DP, Rodriguez LV. Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress-induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study. Neurourol Urodyn. 2020 Feb;39(2):603-612. doi: 10.1002/nau.24270. Epub 2020 Jan 13. [PMID: 31944369] [PMC7043234]
Keywords: animal model; exercise; interstitial cystitis/bladder pain syndrome; psychological stress.

Urinary fungi associated with urinary symptom severity among women with interstitial cystitis/bladder pain syndrome (IC/BPS).

Nickel JC, Stephens A, Landis JR, Mullins C, van Bokhoven A, Anger JT, Ackerman AL, Kim J, Sutcliffe S, Krol JE, Sen B, Hammond J, Ehrlich GD; Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Urinary fungi associated with urinary symptom severity among women with interstitial cystitis/bladder pain syndrome (IC/BPS). World J Urol. 2020 Feb;38(2):433-446. doi: 10.1007/s00345-019-02764-0. Epub 2019 Apr 26. [PMID: 31028455] [PMC6815247]
Keywords: Bladder pain syndrome; Flares; Fungal; Interstitial cystitis; Mycobiome.

A MAPP network case-control study of urological chronic pelvic pain compared with nonurological pain conditions.

Afari N, Buchwald D, Clauw D, Hong B, Hou X, Krieger JN, Mullins C, Stephens-Shields AJ, Gasperi M, Williams DA; MAPP Research Network. A MAPP network case-control study of urological chronic pelvic pain compared with nonurological pain conditions. Clin J Pain. 2020 Jan;36(1):8-15. doi: 10.1097/AJP.0000000000000769. Epub 2019 Sep 26. [PMID: 31794439] [PMC7055954]
Keywords: catastrophizing, chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, pelvic pain.

Assessing somatization in urologic chronic pelvic pain syndrome.

North CS, Hong BA, Lai HH, Alpers DH. Assessing somatization in urologic chronic pelvic pain syndrome. BMC Urol. 2019 Dec 10;19(1):130. doi: 10.1186/s12894-019-0556-3. [PMID: 31823813] [PMC6902613]
Keywords: Chronic prostatitis; Interstitial cystitis; Polysymptomatic; Polysyndromic; Psychiatric diagnosis; Psychoform; Somatization disorder; Somatoform; Symptom screening; Urological chronic pelvic pain syndrome.

Changes in whole body pain intensity and widespreadness during urologic chronic pelvic pain syndrome flares-Findings from one site of the MAPP study.

Xu T, Lai HH, Pakpahan R, Vetter J, Andriole GL, Bradley C, Naliboff BD, Colditz GA, Sutcliffe S. Changes in whole body pain intensity and widespreadness during urologic chronic pelvic pain syndrome flares-Findings from one site of the MAPP study. Neurourol Urodyn. 2019 Nov;38(8):2333-2350. doi: 10.1002/nau.24150. Epub 2019 Sep 4. [PMID: 31483064] [PMC9188843]
Keywords: chronic prostatitis; flares; interstitial cystitis; longitudinal study; symptom exacerbations.

Flares of chronic pelvic pain syndrome: lessons learned from the MAPP Research Network.

Kessler TM. Flares of chronic pelvic pain syndrome: lessons learned from the MAPP Research Network. BJU Int. 2019 Sep;124(3):360-361. doi: 10.1111/bju.14843. [PMID: 31436041] [ZORA 174299]
Keywords: chronic disease; chronic pain; pelvic pain.

A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Sutcliffe S, Gallop R, Henry Lai HH, Andriole GL, Bradley CS, Chelimsky G, Chelimsky T, Quentin Clemens J, Colditz GA, Erickson B, Griffith JW, Kim J, Krieger JN, Labus J, Naliboff BD, Rodriguez LV, Sutherland SE, Taple BJ, Landis JR. A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int. 2019 Sep;124(3):522-531. doi: 10.1111/bju.14783. Epub 2019 May 29. [PMID: 31012513] [PMC6706296]
Keywords: epidemiology; interstitial cystitis; prostatitis; symptom flare-up.

Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor.

Aguiniga LM, Yang W, Yaggie RE, Schaeffer AJ, Klumpp DJ; MAPP Research Network Study Group. Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor. Am J Physiol Regul Integr Comp Physiol. 2019 Aug 1;317(2):R289-R300. doi: 10.1152/ajpregu.00029.2019. Epub 2019 Apr 24. [PMID: 31017816] [PMC6732428]
Keywords: AOAH; AhR; CRF; arachidonic acid; interstitial cystitis; stress.

Impact of early adverse life events and sex on functional brain networks in patients with urological chronic pelvic pain syndrome (UCPPS): A MAPP Research Network study.

Gupta A, Bhatt RR, Naliboff BD, Kutch JJ, Labus JS, Vora PP, Alaverdyan M, Schrepf A, Lutgendorf S, Mayer EA; MAPP Research Network. Impact of early adverse life events and sex on functional brain networks in patients with urological chronic pelvic pain syndrome (UCPPS): A MAPP Research Network study. PLoS One. 2019 Jun 20;14(6):e0217610. doi: 10.1371/journal.pone.0217610. eCollection 2019. [PMID: 31220089] [PMC6586272]
Keywords: centrality; pain; eigenvectors; neural networks; neuroimaging; caudate nucleus; urology; basal ganglia.

Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study.

Harte SE, Schrepf A, Gallop R, Kruger GH, Lai HHH, Sutcliffe S, Halvorson M, Ichesco E, Naliboff BD, Afari N, Harris RE, Farrar JT, Tu F, Landis JR, Clauw DJ; MAPP Research Network. Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study. Pain. 2019 Jun;160(6):1270-1280. doi: 10.1097/j.pain.0000000000001505. [PMID: 31050659] [PMC6527452]
Keywords: Quantitative sensory testing; Pressure pain threshold; Interstitial cystitis; Bladder pain syndrome; Chronic prostatitis; Chronic pelvic pain syndrome; Central sensitization.

Optimization of DNA extraction from human urinary samples for mycobiome community profiling.

Ackerman AL, Anger JT, Khalique MU, Ackerman JE, Tang J, Kim J, Underhill DM, Freeman MR; NIH Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP). Optimization of DNA extraction from human urinary samples for mycobiome community profiling. PLoS One. 2019 Apr 25;14(4):e0210306. doi: 10.1371/journal.pone.0210306. eCollection 2019. [PMID: 31022216] [PMC6483181]
Keywords: urine; DNA isolation; centrifugation; DNA extraction; bacteria; fungi; cell disruption; specimen disruption.

Management of symptom flares and patient-reported flare triggers in interstitial cystitis/bladder pain syndrome (ic/bps)-findings from one site of the MAPP Research Network.

Lai HH, Vetter J, Song J, Andriole GL, Colditz GA, Sutcliffe S. Management of symptom flares and patient-reported flare triggers in interstitial cystitis/bladder pain syndrome (ic/bps)-findings from one site of the MAPP Research Network. Urology. 2019 Apr;126:24-33. doi: 10.1016/j.urology.2019.01.012. Epub 2019 Jan 22. [PMID: 30682464] [PMC6874838]
Keywords: cystitis; interstitial; self management; self report; symptom flare up.

Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.

Clemens JQ, Mullins C, Ackerman AL, Bavendam T, van Bokhoven A, Ellingson BM, Harte SE, Kutch JJ, Lai HH, Martucci KT, Moldwin R, Naliboff BD, Pontari MA, Sutcliffe S, Landis JR; MAPP Research Network Study Group. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol. 2019 Mar;16(3):187-200. doi: 10.1038/s41585-018-0135-5. [PMID: 30560936] [PMC6800057]
Keywords: bladder/bladder disease; Urologic chronic pelvic pain syndromes; chronic pain; prostatitis.

A culture-independent analysis of the microbiota of female interstitial cystitis/bladder pain syndrome participants in the MAPP Research Network.

Nickel JC, Stephens-Shields AJ, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Henderson JP, Sen B, Krol JE, Ehrlich GD; MAPP Research Network. A culture-independent analysis of the microbiota of female interstitial cystitis/bladder pain syndrome participants in the MAPP Research Network. J Clin Med. 2019 Mar 26;8(3):415. doi: 10.3390/jcm8030415. [PMID: 30917614] [PMC6462969]
Keywords: bladder pain syndrome; infection; interstitial cystitis; microbiome; microbiota.

Symptom duration in patients with urologic chronic pelvic pain syndrome is not associated with pain severity, nonurologic syndromes and mental health symptoms: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network Study.

Rodríguez LV, Stephens AJ, Clemens JQ, Buchwald D, Yang C, Lai HH, Krieger JN, Newcomb C, Bradley CS, Naliboff B; MAPP Research Network. Symptom duration in patients with urologic chronic pelvic pain syndrome is not associated with pain severity, nonurologic syndromes and mental health symptoms: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network Study. Urology. 2019 Feb;124:14-22. doi: 10.1016/j.urology.2018.11.015. Epub 2018 Nov 16. [PMID: 30452963] [PMC7037673]
Keywords: chronic pain; mental disorders; pain measurement; pelvic pain; severity of illness index; symptom assessment.

2018

Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS): A MAPP Network study.

Woodworth DC, Dagher A, Curatolo A, Sachdev M, Ashe-McNalley C, Naliboff BD, Labus JS, Landis JR, Kutch JJ, Mayer EA, Lee RS, Moses MA, Ellingson BM; MAPP Research Network. Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS): A MAPP Network study. PLoS One. 2018 Dec 5;13(12):e0206807. doi: 10.1371/journal.pone.0206807. eCollection 2018. [PMID: 30517112] [PMC6281196]
Keywords: Urinary biomarkers; Diffusion tensor imaging; Brainstem; Pain; Urine; Biomarkers; Brain; Neuroimaging.

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

Schrepf A, Williams DA, Gallop R, Naliboff BD, Basu N, Kaplan C, Harper DE, Landis JR, Clemens JQ, Strachan E, Griffith JW, Afari N, Hassett A, Pontari MA, Clauw DJ, Harte SE; MAPP Research Network. Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study. Pain. 2018 Oct;159(10):2002-2011. doi: 10.1097/j.pain.0000000000001299. [PMID: 29863527] [PMC6705610]
Keywords: Interstitial cystitis/painful bladder syndrome; Factor analysis; statistical; Fibromyalgia; Central nervous system sensitization; Interoception.

Adverse childhood experiences and symptoms of urologic chronic pelvic pain syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study.

Schrepf A, Naliboff B, Williams DA, Stephens-Shields AJ, Landis JR, Gupta A, Mayer E, Rodriguez LV, Lai H, Luo Y, Bradley C, Kreder K, Lutgendorf SK; MAPP Research Network. Adverse childhood experiences and symptoms of urologic chronic pelvic pain syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study. Ann Behav Med. 2018 Sep 13;52(10):865-877. doi: 10.1093/abm/kax060. [PMID: 30212850] [PMC6135957]
Keywords: Interstitial Cystitis/Painful Bladder Syndrome; Chronic Prostatitis with Chronic Pelvic Pain Syndrome; Psychological Trauma; Sexual Abuse.

A MAPP Network study: overexpression of tumor necrosis factor-? in mouse urothelium mimics interstitial cystitis.

Yang W, Searl TJ, Yaggie R, Schaeffer AJ, Klumpp DJ. A MAPP Network study: overexpression of tumor necrosis factor-? in mouse urothelium mimics interstitial cystitis. Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F36-F44. doi: 10.1152/ajprenal.00075.2017. Epub 2018 Feb 21. [PMID: 29465304] [PMC6087793]
Keywords: TNF; interstitial cystitis; pelvic pain; transgenic mouse model.

Correlates of health care seeking activities in patients with urological chronic pelvic pain syndromes: findings from the MAPP Cohort.

Clemens JQ, Stephens-Shields A, Naliboff BD, Lai HH, Rodriguez L, Krieger JN, Williams DA, Kusek JW, Landis JR; MAPP Research Network. Correlates of health care seeking activities in patients with urological chronic pelvic pain syndromes: findings from the MAPP Cohort. J Urol. 2018 Jul;200(1):136-140. doi: 10.1016/j.juro.2017.12.055. Epub 2018 Jan 4. [PMID: 29307682] [PMC6002941]
Keywords: cystitis; interstitial; patient acceptance of health care; pelvic pain; prostate; urinary bladder.

Physical examination for men and women with urologic chronic pelvic pain syndrome: A MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Network Study.

Yang CC, Miller JL, Omidpanah A, Krieger JN. Physical examination for men and women with urologic chronic pelvic pain syndrome: A MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Network Study. Urology. 2018 Jun;116:23-29. doi: 10.1016/j.urology.2018.03.021. Epub 2018 Mar 28. [PMID: 29604315] [PMC6237096]
Keywords: algorithms; anthropometry; chronic fatigue syndrome; chronic pain; cross-sectional studies; cystitis; feasibility studies; palpation; pelvic floor disorders; pelvic pain; prostatitis; pudendal nerve.

A case-crossover study of urological chronic pelvic pain syndrome flare triggers in the MAPP Research Network.

Sutcliffe S, Jemielita T, Lai HH, Andriole GL, Bradley CS, Clemens JQ, Gallop R, Hooton TM, Kreder KJ, Krieger JN, Kusek JW, Labus J, Lucia MS, Mackey S, Naliboff BD, Robinson NA, Rodriguez LV, Stephens-Shields A, van Bokhoven A, Wolin KY, Yan Y, Yang CC, Landis JR, Colditz GA; MAPP Research Network. A case-crossover study of urological chronic pelvic pain syndrome flare triggers in the MAPP Research Network. J Urol. 2018 May;199(5):1245-1251. doi: 10.1016/j.juro.2017.12.050. Epub 2017 Dec 27. [PMID: 29288643] [PMC5911194]
Keywords: cystitis; interstitial; prostatitis; surveys and questionnaires; symptom flare up; urinary bladder.

Sub-noxious Intravesical lipopolysaccharide triggers bladder inflammation and symptom onset in a transgenic autoimmune cystitis model: A MAPP Network Animal Study.

Kogan P, Xu S, Wang Y, O’Donnell MA, Lutgendorf SK, Bradley CS, Schrepf A, Kreder KJ, Luo Y. Sub-noxious Intravesical lipopolysaccharide triggers bladder inflammation and symptom onset in a transgenic autoimmune cystitis model: A MAPP Network Animal Study. Sci Rep. 2018 Apr 26;8(1):6573. doi: 10.1038/s41598-018-24833-x. [PMID: 29700406] [PMC5919907]
Keywords: autoimmunity; experimental models of disease.

Acyloxyacyl hydrolase modulates pelvic pain severity.

Yang W, Yaggie RE, Jiang MC, Rudick CN, Done J, Heckman CJ, Rosen JM, Schaeffer AJ, Klumpp DJ. Acyloxyacyl hydrolase modulates pelvic pain severity. Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R353-R365. doi: 10.1152/ajpregu.00239.2017. Epub 2017 Nov 8. [PMID: 29118019] [PMC5899250]
Keywords: AOAH; QTL; allodynia; pelvic pain; pseudorabies virus.

The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

Gao Y, Zhang R, Chang HH, Rodríguez LV. The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. Neurourol Urodyn. 2018 Feb;37(2):673-680. doi: 10.1002/nau.23374. Epub 2017 Aug 9. [PMID: 28792095] [PMC5988434]
Keywords: bladder hypersensitivity; cystometrogram; hyperalgesia; interstitial cystitis; visceromeotor reflex; water avoidance stress.

2017

Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study.

Harper DE, Ichesco E, Schrepf A, Halvorson M, Puiu T, Clauw DJ, Harris RE, Harte SE; MAPP Research Network. Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study. Neuroimage Clin. 2017 Nov 15;17:570-578. doi: 10.1016/j.nicl.2017.11.014. eCollection 2018. [PMID: 29201643] [PMC5702874]
Keywords: Centralized pain; Choline; Gamma aminobutyric acid (GABA); Interstitial cystitis; MAPP; Proton magnetic resonance spectroscopy.

Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study.

Lai HH, Shen B, Vijairania P, Zhang X, Vogt SK, Gereau RW 4th. Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study. BJU Int. 2017 Oct;120(4):576-583. doi: 10.1111/bju.13924. Epub 2017 Jun 29. [PMID: 28581681] [PMC5716917]
Keywords: bladder pain; cyclophosphamide cystitis; interstitial cystitis; vascular endothelial growth factor anti-VEGF.

Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study.

Kutch JJ, Ichesco E, Hampson JP, Labus JS, Farmer MA, Martucci KT, Ness TJ, Deutsch G, Apkarian AV, Mackey SC, Klumpp DJ, Schaeffer AJ, Rodriguez LV, Kreder KJ, Buchwald D, Andriole GL, Lai HH, Mullins C, Kusek JW, Landis JR, Mayer EA, Clemens JQ, Clauw DJ, Harris RE; MAPP Research Network. Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study. Pain. 2017 Oct;158(10):1979-1991. doi: 10.1097/j.pain.0000000000001001. [PMID: 28692006] [PMC5964335]
Keywords: Centralized; Chronic; Pain; fMRI; Widespread; Fibromyalgia; Pelvic; VBM; Connectivity.

Clinical and psychosocial predictors of urological chronic pelvic pain symptom change in 1 year: a prospective study from the MAPP Research Network.

Naliboff BD, Stephens AJ, Lai HH, Griffith JW, Clemens JQ, Lutgendorf S, Rodriguez LV, Newcomb C, Sutcliffe S, Guo W, Kusek JW, Landis JR; MAPP Research Network. Clinical and psychosocial predictors of urological chronic pelvic pain symptom change in 1 year: a prospective study from the MAPP Research Network. J Urol. 2017 Oct;198(4):848-857. doi: 10.1016/j.juro.2017.05.065. Epub 2017 May 18. [PMID: 28528930] [PMC5720154]
Keywords: cystitis; interstitial; pelvic pain; prostate; prostatitis; urinary bladder.

Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

Wang Z, Chang HH, Gao Y, Zhang R, Guo Y, Holschneider DP, Rodriguez LV. Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. PLoS One. 2017 Sep 8;12(9):e0182976. doi: 10.1371/journal.pone.0182976. eCollection 2017. [PMID: 28886046] [PMC5590813]
Keywords: Bladder; Urination; Psychological stress; Sensory perception; Pain; Motor cortex; Pain sensation; Thalamus.

Characterization of whole-body pain in urological chronic pelvic pain syndrome at baseline: A MAPP Research Network Study.

Lai HH, Jemielita T, Sutcliffe S, Bradley CS, Naliboff B, Williams DA, Gereau RW 4th, Kreder K, Clemens JQ, Rodriguez LV, Krieger JN, Farrar JT, Robinson N, Landis JR; MAPP Research Network. Characterization of whole-body pain in urological chronic pelvic pain syndrome at baseline: A MAPP Research Network Study. J Urol. 2017 Sep;198(3):622-631. doi: 10.1016/j.juro.2017.03.132. Epub 2017 Mar 31. [PMID: 28373134] [PMC5562525]
Keywords: cystitis; interstitial; pelvic pain; prostate; prostatitis; urinary bladder.

Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Dagher A, Curatolo A, Sachdev M, Stephens AJ, Mullins C, Landis JR, van Bokhoven A, El-Hayek A, Froehlich JW, Briscoe AC, Roy R, Yang J, Pontari MA, Zurakowski D, Lee RS, Moses MA; MAPP Research Network. Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int. 2017 Jul;120(1):130-142. doi: 10.1111/bju.13832. Epub 2017 Apr 11. [PMID: 28263447] [PMC5951631]
Keywords: Lipocalin 2 (also known as NGAL); Multidisciplinary Approach to the Study of Chronic Pelvic Pain; matrix metalloproteinase; neutrophil gelatinase associated lipocalin; vascular endothelial growth factor; vascular endothelial growth factor receptor 1.

Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study.

Kutch JJ, Labus JS, Harris RE, Martucci KT, Farmer MA, Fenske S, Fling C, Ichesco E, Peltier S, Petre B, Guo W, Hou X, Stephens AJ, Mullins C, Clauw DJ, Mackey SC, Apkarian AV, Landis JR, Mayer EA; MAPP Research Network. Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study. Pain. 2017 Jun;158(6):1069-1082. doi: 10.1097/j.pain.0000000000000886. [PMID: 28328579] [PMC5435510]
Keywords: Neuroimaging; Prediction; Chronic pain; Urologic pain.

Evidence for the role of mast cells in cystitis-associated lower urinary tract dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study.

Wang X, Liu W, O’Donnell M, Lutgendorf S, Bradley C, Schrepf A, Liu L, Kreder K, Luo Y. Evidence for the role of mast cells in cystitis-associated lower urinary tract dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS One. 2016 Dec 21;11(12):e0168772. doi: 10.1371/journal.pone.0168772. eCollection 2016. [PMID: 28002455] [PMC5176179]
Category: Mast cells; Bladder; Cystitis; Mouse models; Inflammation; Urination; Habits; Pain.

Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study.

Huang L, Kutch JJ, Ellingson BM, Martucci KT, Harris RE, Clauw DJ, Mackey S, Mayer EA, Schaeffer AJ, Apkarian AV, Farmer MA; MAPP Research Network. Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study. Pain. 2016 Dec;157(12):2782-2791. doi: 10.1097/j.pain.0000000000000703. [PMID: 27842046] [PMC5117992]
Keywords: Pain; Urological; Pelvic; Irritable bowel syndrome; Diffusion tensor imaging.

Symptom variability and early symptom regression in the MAPP study: a prospective study of urological chronic pelvic pain syndrome.

Stephens-Shields AJ, Clemens JQ, Jemielita T, Farrar J, Sutcliffe S, Hou X, Landis JR; MAPP Research Network. Symptom variability and early symptom regression in the MAPP study: a prospective study of urological chronic pelvic pain syndrome. J Urol. 2016 Nov;196(5):1450-1455. doi: 10.1016/j.juro.2016.04.070. Epub 2016 Apr 27. [PMID: 27131464] [PMC5069105]
Keywords: cystitis; epidemiologic research design; interstitial; pain; prostate; symptom assessment.

Transgenic mice expressing mcp-1 by the urothelium demonstrate bladder hypersensitivity, pelvic pain and voiding dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study.

Xu S, Wang X, Wang Y, Lutgendorf S, Bradley C, Schrepf A, Kreder K, O’Donnell M, Luo Y. Transgenic mice expressing mcp-1 by the urothelium demonstrate bladder hypersensitivity, pelvic pain and voiding dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS One. 2016 Sep 29;11(9):e0163829. doi: 10.1371/journal.pone.0163829. eCollection 2016. [PMID: 27684718] [PMC5042429]
Keywords: Bladder; Mouse models; Inflammation; Pain; Genetically modified animals; Cystitis; Habits; Urination.

Bladder distension increases blood flow in pain related brain structures in subjects with interstitial cystitis.

Deutsch G, Deshpande H, Frölich MA, Lai HH, Ness TJ. Bladder distension increases blood flow in pain related brain structures in subjects with interstitial cystitis. J Urol. 2016 Sep;196(3):902-10. doi: 10.1016/j.juro.2016.03.135. Epub 2016 Mar 24. [PMID: 27018508] [PMC5014638]
Keywords: brain; cerebrovascular circulation; cystitis, interstitial; pain; urinary bladder.

Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a multidisciplinary approach to the study of chronic pelvic pain (MAPP) research network cohort.

Parker KS, Crowley JR, Stephens-Shields AJ, van Bokhoven A, Lucia MS, Lai HH, Andriole GL, Hooton TM, Mullins C, Henderson JP. Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a multidisciplinary approach to the study of chronic pelvic pain (MAPP) research network cohort. EBioMedicine. 2016 May;7:167-74. doi: 10.1016/j.ebiom.2016.03.040. Epub 2016 Mar 31. [PMID: 27322470] [PMC4909380]
Keywords: biomarkers; cystitis; interstitial; mass spectrometry; pain measurement; steroids; steroids/urine; sulfates; sulfates/urine.

Cognitive - behavioral therapy in central sensitivity syndromes.

Williams DA. Cognitive-behavioral therapy in central sensitivity syndromes. Curr Rheumatol Rev. 2016;12(1):2-12. doi: 10.2174/157339711201160303103241. [PMID: 26717953] [2016]
Keywords: BioPsychoSocial; central sensitivity syndromes; chronic overlapping pain conditions; cognitive behavioral therapy.

Pain and urinary symptoms should not be combined into a single score: psychometric findings from the MAPP Research Network.

Griffith JW, Stephens-Shields AJ, Hou X, Naliboff BD, Pontari M, Edwards TC, Williams DA, Clemens JQ, Afari N, Tu F, Lloyd RB, Patrick DL, Mullins C, Kusek JW, Sutcliffe S, Hong BA, Lai HH, Krieger JN, Bradley CS, Kim J, Landis JR. Pain and urinary symptoms should not be combined into a single score: psychometric findings from the MAPP Research Network. J Urol. 2016 Apr;195(4 Pt 1):949-54. doi: 10.1016/j.juro.2015.11.012. Epub 2015 Nov 14. [PMID: 26585679] [PMC4867140]
Keywords: chronic pain; cystitis, interstitial; factor analysis, statistical; prostatitis; urinary bladder.

Alterations in connectivity on functional magnetic resonance imaging with provocation of lower urinary tract symptoms: A MAPP Research Network Feasibility Study of Urological Chronic Pelvic Pain Syndromes.

Kleinhans NM, Yang CC, Strachan ED, Buchwald DS, Maravilla KR. Alterations in connectivity on functional magnetic resonance imaging with provocation of lower urinary tract symptoms: A MAPP Research Network Feasibility Study of Urological Chronic Pelvic Pain Syndromes. J Urol. 2016 Mar;195(3):639-45. doi: 10.1016/j.juro.2015.09.092. Epub 2015 Oct 22. [PMID: 26497778] [PMC5035686]
Keywords: brain; cystitis; interstitial; magnetic resonance imaging; pain; urinary bladder.

Assessment of the lower urinary tract microbiota during symptom flare in women with urologic chronic pelvic pain syndrome: A MAPP Network Study.

Nickel JC, Stephens A, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Ehrlich GD; MAPP Research Network. Assessment of the lower urinary tract microbiota during symptom flare in women with urologic chronic pelvic pain syndrome: A MAPP Network Study. J Urol. 2016 Feb;195(2):356-62. doi: 10.1016/j.juro.2015.09.075. Epub 2015 Sep 26. [PMID: 26410734] [PMC4770794]
Keywords: cystitis; infection; interstitial; microbiota; symptom assessment.

Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network.

Alger JR, Ellingson BM, Ashe-McNalley C, Woodworth DC, Labus JS, Farmer M, Huang L, Apkarian AV, Johnson KA, Mackey SC, Ness TJ, Deutsch G, Harris RE, Clauw DJ, Glover GH, Parrish TB, Hollander Jd, Kusek JW, Mullins C, Mayer EA; MAPP Research Network Investigators. Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network. Neuroimage Clin. 2016 Jan 6;12:65-77. doi: 10.1016/j.nicl.2015.12.009. eCollection 2016. [PMID: 27408791] [PMC4925887]
Keywords: Brain; Diffusion tensor imaging [DTI]; Functional magnetic resonance imaging; Magnetic resonance imaging; TransMAPP; Urologic chronic pelvic pain syndromes.

Altered brain connectivity in dysmenorrhea: pain modulation and the motor cortex.

Kutch JJ, Tu FF. Altered brain connectivity in dysmenorrhea: pain modulation and the motor cortex. Pain. 2016 Jan;157(1):5-6. doi: 10.1097/j.pain.0000000000000364. [PMID: 26683107] [PMC4941100]
Keywords: brain; brain mapping; dysmenorrhea; magnetic resonance imaging; motor cortex; Nerve Net; neural pathways.

Painful bladder filling and painful urgency are distinct characteristics in men and women with urological chronic pelvic pain syndromes: A MAPP Research Network Study.

Lai HH, Krieger JN, Pontari MA, Buchwald D, Hou X, Landis JR; MAPP Research Network. Painful bladder filling and painful urgency are distinct characteristics in men and women with urological chronic pelvic pain syndromes: A MAPP Research Network Study. J Urol. 2015 Dec;194(6):1634-41. doi: 10.1016/j.juro.2015.05.105. Epub 2015 Jul 17. [PMID: 26192257] [PMC4669971]
Keywords: cystitis; interstitial; pain; prostatitis; questionnaires; urinary bladder.

Unique microstructural changes in the brain associated with urological chronic pelvic pain syndrome (UCPPS) revealed by diffusion tensor MRI, super-resolution track density imaging, and statistical parameter mapping: A MAPP Network Neuroimaging Study.

Woodworth D, Mayer E, Leu K, Ashe-McNalley C, Naliboff BD, Labus JS, Tillisch K, Kutch JJ, Farmer MA, Apkarian AV, Johnson KA, Mackey SC, Ness TJ, Landis JR, Deutsch G, Harris RE, Clauw DJ, Mullins C, Ellingson BM; MAPP Research Network. Unique microstructural changes in the brain associated with urological chronic pelvic pain syndrome (UCPPS) revealed by diffusion tensor MRI, super-resolution track density imaging, and statistical parameter mapping: A MAPP Network Neuroimaging Study. PLoS One. 2015 Oct 13;10(10):e0140250. doi: 10.1371/journal.pone.0140250. eCollection 2015. [PMID: 26460744] [PMC4604194]
Keywords: Pain; Central nervous system; Corpus callosum; Diffusion tensor imaging; Basal ganglia; Microstructure; Anisotropy; Pain sensation.

The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network.

Martucci KT, Shirer WR, Bagarinao E, Johnson KA, Farmer MA, Labus JS, Apkarian AV, Deutsch G, Harris RE, Mayer EA, Clauw DJ, Greicius MD, Mackey SC. The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network. Pain. 2015 Sep;156(9):1755-1764. doi: 10.1097/j.pain.0000000000000238. [PMID: 26010458] [PMC4545714]
Keywords: UCPPS; Interstitial cystitis; Bladder pain syndrome; Posterior cingulate cortex; Default mode network [DMN]; Precuneus; Dual regression; Resting state; fMRI.

Search for microorganisms in men with urologic chronic pelvic pain syndrome: a culture-independent analysis in the MAPP Research Network.

Nickel JC, Stephens A, Landis JR, Chen J, Mullins C, van Bokhoven A, Lucia MS, Melton-Kreft R, Ehrlich GD; MAPP Research Network. Search for microorganisms in men with urologic chronic pelvic pain syndrome: a culture-independent analysis in the MAPP Research Network. J Urol. 2015 Jul;194(1):127-35. doi: 10.1016/j.juro.2015.01.037. Epub 2015 Jan 14. [PMID: 25596358] [PMC4475477]
Keywords: chronic pain; infection; microbiota; pelvic pain; prostatitis.

Urological chronic pelvic pain syndrome flares and their impact: qualitative analysis in the MAPP network.

Sutcliffe S, Bradley CS, Clemens JQ, James AS, Konkle KS, Kreder KJ, Lai HH, Mackey SC, Ashe-McNalley CP, Rodriguez LV, Barrell E, Hou X, Robinson NA, Mullins C, Berry SH. Urological chronic pelvic pain syndrome flares and their impact: qualitative analysis in the MAPP network. Int Urogynecol J. 2015 Jul;26(7):1047-60. doi: 10.1007/s00192-015-2652-6. Epub 2015 Mar 20. [PMID: 25792349] [PMC4489981]
Keywords: Urological chronic pelvic pain syndrome; Interstitial cystitis; Bladder pain syndrome; Symptom exacerbation; Flare; Focus group.

Brain white matter abnormalities in female interstitial cystitis/bladder pain syndrome: A MAPP Network Neuroimaging Study.

Farmer MA, Huang L, Martucci K, Yang CC, Maravilla KR, Harris RE, Clauw DJ, Mackey S, Ellingson BM, Mayer EA, Schaeffer AJ, Apkarian AV; MAPP Research Network. Brain white matter abnormalities in female interstitial cystitis/bladder pain syndrome: A MAPP Network Neuroimaging Study. J Urol. 2015 Jul;194(1):118-26. doi: 10.1016/j.juro.2015.02.082. Epub 2015 Feb 21. [PMID: 25711200] [PMC4475466]
Keywords: cystitis; diffusion tensor imaging; interstitial; pain; urinary bladder; white matter.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.

Kutch JJ, Yani MS, Asavasopon S, Kirages DJ, Rana M, Cosand L, Labus JS, Kilpatrick LA, Ashe-McNalley C, Farmer MA, Johnson KA, Ness TJ, Deutsch G, Harris RE, Apkarian AV, Clauw DJ, Mackey SC, Mullins C, Mayer EA. Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study. Neuroimage Clin. 2015 Jun 5;8:493-502. doi: 10.1016/j.nicl.2015.05.013. eCollection 2015. [PMID: 26106574] [PMC4474411]
Keywords: brain mapping; Brief Pain Inventory; chronic prostatitis; functional magnetic resonance imaging; Functional Neuroimaging; image processing; magnetic resonance imaging; motoneuron; motor control; motor cortex; muscle contraction; nerve cell network; Nerve Net; neuroimaging; nuclear magnetic resonance imaging; pathophysiology; pelvis pain syndrome; posterior insula; prostatitis; resting state network.

Animal models of urologic chronic pelvic pain syndromes: findings from the multidisciplinary approach to the study of chronic pelvic pain research network.

Lai H, Gereau RW 4th, Luo Y, O’Donnell M, Rudick CN, Pontari M, Mullins C, Klumpp DJ. Animal models of urologic chronic pelvic pain syndromes: findings from the multidisciplinary approach to the study of chronic pelvic pain research network. Urology. 2015 Jun;85(6):1454-65. doi: 10.1016/j.urology.2015.03.007. [PMID: 26099889] [PMC4479414]
Keywords: interstitial cystitis; chronic prostatitis; animal models; pain models; translational research; pelvic pain.

Widespread psychosocial difficulties in men and women with urologic chronic pelvic pain syndromes: case-control findings from the multidisciplinary approach to the study of chronic pelvic pain research network.

Naliboff BD, Stephens AJ, Afari N, Lai H, Krieger JN, Hong B, Lutgendorf S, Strachan E, Williams D; MAPP Research Network. Widespread psychosocial difficulties in men and women with urologic chronic pelvic pain syndromes: case-control findings from the multidisciplinary approach to the study of chronic pelvic pain research network. Urology. 2015 Jun;85(6):1319-27. doi: 10.1016/j.urology.2015.02.047. [PMID: 26099876] [PMC4479402]
Keywords: chronic pain; pelvic pain; severity of illness index; urologic diseases.

Comparison of baseline urological symptoms in men and women in the MAPP research cohort.

Clemens JQ, Clauw DJ, Kreder K, Krieger JN, Kusek JW, Lai HH, Rodriguez L, Williams DA, Hou X, Stephens A, Landis JR; MAPP Research Network. Comparison of baseline urological symptoms in men and women in the MAPP research cohort. J Urol. 2015 May;193(5):1554-8. doi: 10.1016/j.juro.2014.11.016. Epub 2014 Nov 13. [PMID: 25463989] [PMC4454891]
Keywords: chronic pain; cystitis; interstitial; pelvic pain; prostatitis.

Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study.

Krieger JN, Stephens AJ, Landis JR, Clemens JQ, Kreder K, Lai HH, Afari N, Rodríguez L, Schaeffer A, Mackey S, Andriole GL, Williams DA; MAPP Research Network. Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study. J Urol. 2015 Apr;193(4):1254-62. doi: 10.1016/j.juro.2014.10.086. Epub 2014 Oct 22. [PMID: 25444992] [PMC4497586]
Keywords: cystitis; female; interstitial; male; questionnaires; urinary bladder.

Changes in symptoms during urologic chronic pelvic pain syndrome symptom flares: findings from one site of the MAPP Research Network.

Sutcliffe S, Colditz GA, Pakpahan R, Bradley CS, Goodman MS, Andriole GL, Lai HH. Changes in symptoms during urologic chronic pelvic pain syndrome symptom flares: findings from one site of the MAPP Research Network. Neurourol Urodyn. 2015 Feb;34(2):188-95. doi: 10.1002/nau.22534. Epub 2013 Nov 23. [PMID: 24273163] [PMC4032370]
Keywords: bladder pain syndrome; chronic pelvic pain syndrome; chronic prostatitis; flare; interstitial cystitis; symptom exacerbation.

Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome.

Kairys AE, Schmidt-Wilcke T, Puiu T, Ichesco E, Labus JS, Martucci K, Farmer MA, Ness TJ, Deutsch G, Mayer EA, Mackey S, Apkarian AV, Maravilla K, Clauw DJ, Harris RE. Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome. J Urol. 2015 Jan;193(1):131-7. doi: 10.1016/j.juro.2014.08.042. Epub 2014 Aug 14. [PMID: 25132239] [PMC4435781]
Keywords: ystitis; interstitial; pain; somatosensory cortex.

Urological chronic pelvic pain syndrome symptom flares: characterisation of the full range of flares at two sites in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Sutcliffe S, Colditz GA, Goodman MS, Pakpahan R, Vetter J, Ness TJ, Andriole GL, Lai HH. Urological chronic pelvic pain syndrome symptom flares: characterisation of the full range of flares at two sites in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int. 2014 Dec;114(6):916-25. doi: 10.1111/bju.12778. Epub 2014 Aug 11. [PMID: 24730356] [PMC4198521]
Keywords: bladder pain syndrome; chronic pelvic pain syndrome; chronic prostatitis; flare; interstitial cystitis; symptom exacerbation.

Evaluation of urinary protein precipitation protocols for the multidisciplinary approach to the study of chronic pelvic pain research network.

Jonscher KR, Osypuk AA, van Bokhoven A, Lucia MS. Evaluation of urinary protein precipitation protocols for the multidisciplinary approach to the study of chronic pelvic pain research network. J Biomol Tech. 2014 Dec;25(4):118-26. doi: 10.7171/jbt.14-2504-004. [PMID: 25365794] [PMC4211279]
Keywords: chemical precipitation; proteomics; quantitation; urine.

Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study.

Bagarinao E, Johnson KA, Martucci KT, Ichesco E, Farmer MA, Labus J, Ness TJ, Harris R, Deutsch G, Apkarian VA, Mayer EA, Clauw DJ, Mackey S. Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study. Pain. 2014 Dec;155(12):2502-2509. doi: 10.1016/j.pain.2014.09.002. Epub 2014 Sep 19. [PMID: 25242566] [PMC4504202]
Keywords: Gray matter density; Machine learning; SVM; Support vector machine; UCPPS.

Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI.

Rudick CN, Taylor AK, Yaggie RE, Schaeffer AJ, Klumpp DJ. Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI. PLoS One. 2014 Nov 18;9(11):e109321. doi: 10.1371/journal.pone.0109321. eCollection 2014. [PMID: 25405579] [PMC4236008]
Keywords: Allodynia; Analgesics; Pain; Bladder; Bacterial pathogens; Urinary tract infections; Antimicrobial resistance; Escherichia coli infections.

Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome.

Kilpatrick LA, Kutch JJ, Tillisch K, Naliboff BD, Labus JS, Jiang Z, Farmer MA, Apkarian AV, Mackey S, Martucci KT, Clauw DJ, Harris RE, Deutsch G, Ness TJ, Yang CC, Maravilla K, Mullins C, Mayer EA. Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome. J Urol. 2014 Sep;192(3):947-55. doi: 10.1016/j.juro.2014.03.093. Epub 2014 Mar 26. [PMID: 24681331] [PMC4432915]
Keywords: brain mapping; cystitis; interstitial; magnetic resonance imaging; pain; urinary bladder.

The MAPP research network: design, patient characterization and operations.

Landis JR, Williams DA, Lucia MS, Clauw DJ, Naliboff BD, Robinson NA, van Bokhoven A, Sutcliffe S, Schaeffer AJ, Rodriguez LV, Mayer EA, Lai HH, Krieger JN, Kreder KJ, Afari N, Andriole GL, Bradley CS, Griffith JW, Klumpp DJ, Hong BA, Lutgendorf SK, Buchwald D, Yang CC, Mackey S, Pontari MA, Hanno P, Kusek JW, Mullins C, Clemens JQ; MAPP Research Network Study Group. The MAPP research network: design, patient characterization and operations. BMC Urol. 2014 Aug 1;14:58. doi: 10.1186/1471-2490-14-58. [PMID: 25085119] [PMC4126395]
Keywords: Urologic chronic pelvic pain syndromes; Interstitial cystitis; Chronic prostatitis; Urine biomarkers; Plasma biomarkers; Non-urologic associated syndromes; Quantitative sensory testing (QST); Neuroimaging.

The MAPP research network: a novel study of urologic chronic pelvic pain syndromes.

Clemens JQ, Mullins C, Kusek JW, Kirkali Z, Mayer EA, Rodríguez LV, Klumpp DJ, Schaeffer AJ, Kreder KJ, Buchwald D, Andriole GL, Lucia MS, Landis JR, Clauw DJ; MAPP Research Network Study Group. The MAPP research network: a novel study of urologic chronic pelvic pain syndromes. BMC Urol. 2014 Aug 1;14:57. doi: 10.1186/1471-2490-14-57. [PMID: 25085007] [PMC4134515]
Keywords: Urological chronic pelvic pain syndromes; Interstitial cystitis; Chronic prostatitis; Translational research; Multi-disciplinary.

Urological symptoms in a subset of patients with urological chronic pelvic pain syndrome and a polysymptomatic, polysyndromic pattern of presentation.

Lai HH, North CS, Andriole GL, Cupps L, Song D, Ness TJ, Hong BA. Urological symptoms in a subset of patients with urological chronic pelvic pain syndrome and a polysymptomatic, polysyndromic pattern of presentation. J Urol. 2014 Jun;191(6):1802-7. doi: 10.1016/j.juro.2013.12.031. Epub 2013 Dec 19. [PMID: 24361369] [PMC4411959]
Keywords: chronic pain; cystitis; interstitial; prostatitis; somatosensory disorders; urinary bladder.

2013

The importance of psychological assessment in chronic pain.

Williams DA. The importance of psychological assessment in chronic pain. Curr Opin Urol. 2013 Nov;23(6):554-9. doi: 10.1097/MOU.0b013e3283652af1. [PMID: 24080806] [PMC4295636]
Keywords: Affect; Cognition; pain perception; modulation.

Development and validation of a pressure-type automated quantitative sensory testing system for point-of-care pain assessment.

Harte SE, Mitra M, Ichesco EA, Halvorson ME, Clauw DJ, Shih AJ, Kruger GH. Development and validation of a pressure-type automated quantitative sensory testing system for point-of-care pain assessment. Med Biol Eng Comput. 2013 Jun;51(6):633-44. doi: 10.1007/s11517-013-1033-x. Epub 2013 Feb 5. [PMID: 23381890] [Sep-13]
Keywords: Chronic pain; Fibromyalgia; MAST; Pressure pain threshold.

Evidence for overlap between urological and nonurological unexplained clinical conditions.

Bullones Rodríguez MÁ, Afari N, Buchwald DS; National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Urological Chronic Pelvic Pain. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2013 Jan;189(1 Suppl):S66-74. doi: 10.1016/j.juro.2012.11.019. [PMID: 23234637] [PMC9159381]
Keywords: urogenital system; fatigue syndrome; chronic; fibromyalgia; irritable bowel syndrome; temporomandibular joint disorders.

Protamine sulfate-induced bladder injury protects from distention induced bladder pain.

Stemler KM, Crock LW, Lai HH, Mills JC, Gereau RW 4th and Mysorekar IU. Protamine sulfate-induced bladder injury protects from distention induced bladder pain. J Urol. 2013 Jan;189(1): 343-51. doi: 10.1016/j.juro.2012.08.189. Epub 2012 Nov 20. [PMID: 23174261] [PMC3662487]
Keywords: urinary bladder; pain; protamines; nociception; inflammation.

2012

Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain.

Crock LW, Kolber BJ, Morgan CD, Sadler KE, Vogt SK, Bruchas MR, Gereau RW 4th. Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain. J Neurosci. 2012 Oct 10;32(41):14217-26. doi: 10.1523/JNEUROSCI.1473-12.2012. [PMID: 23055491] [PMC3494864]
Keywords: amygdala/physiology; Grm5 protein; metabotropic glutamate 5; NAP kinase signaling system; pain measurement; visceral pain.

The siderophore yersiniabactin binds copper to protect pathogens during infection.

Chaturvedi KS, Hung CS, Crowley JR, Stapleton AE, Henderson JP. The siderophore yersiniabactin binds copper to protect pathogens during infection. Nat Chem Biol. 2012 Aug;8(8):731-6. doi: 10.1038/nchembio.1020. Epub 2012 Jul 8. [PMID: 22772152] [PMC3600419]
Keywords: Bacterial pathogenesis; Chemical genetics; Iron.

Polysymptomatic, polysyndromic presentation of patients with urological chronic pelvic pain syndrome.

Lai HH, North CS, Andriole GL, Sayuk GS, Hong BA. Polysymptomatic, polysyndromic presentation of patients with urological chronic pelvic pain syndrome. J Urol. 2012 Jun;187(6):2106-12. doi: 10.1016/j.juro.2012.01.081. Epub 2012 Apr 12. [PMID: 22503014] [PMC3957225]
Keywords: urinary bladder; prostate; cystitis, interstitial; prostatitis; somatization disorders.

O-antigen modulates infection-induced pain states.

Rudick CN, Jiang M, Yaggie RE, Pavlov VI, Done J, Heckman CJ, Whitfield C, Schaeffer AJ, Klumpp DJ. O-antigen modulates infection-induced pain states. PLoS One. 2012;7(8):e41273. doi: 10.1371/journal.pone.0041273. Epub 2012 Aug 10. [PMID: 22899994] [PMC3416823]
Keywords: Pain; Allodynia; Bladder; Inflammation; Spinal cord; Neutrophils; Bacterial pathogens; Hypersensitivity.

2011

Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production.

Lv H, Henderson JP. Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production. J Proteome Res. 2011 Dec 2;10(12):5547-54. doi: 10.1021/pr200756n. Epub 2011 Nov 15. [PMID: 22035238] [PMC3626101]
Keywords: metabolomics; siderophore; yersiniabactin; Escherichia coli; primary metabolism; ybtU; ybtA; arginine biosynthesis.

Development of an integrated metabolomic profiling approach for infectious diseases research.

Lv H, Hung CS, Chaturvedi KS, Hooton TM, Henderson JP. Development of an integrated metabolomic profiling approach for infectious diseases research. Analyst. 2011 Nov 21;136(22):4752-63. doi: 10.1039/c1an15590c. Epub 2011 Sep 16. [PMID: 21922104] [PMC3746514]
Keywords: integrated approach; LC-MS; untargeted urine metabolomics; urinary tract infection; Escherichia coli; infectious diseases.

Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.

Lai HH, Qiu CS, Crock LW, Morales MEP, Ness TJ, Gereau RW 4th. Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder. Pain. 2011 Sep;152(9):2117-2124. doi: 10.1016/j.pain.2011.05.017. Epub 2011 Jun 25. [PMID: 21705143] [PMC3157542]
Keywords: Urinary bladder; Visceral pain; Inflammatory pain; Visceromotor response; ERK signaling; Central sensitization.

Intravesical dimethyl sulfoxide inhibits acute and chronic bladder inflammation in transgenic experimental autoimmune cystitis models.

Kim R, Liu W, Chen X, Kreder KJ, Luo Y. Intravesical dimethyl sulfoxide inhibits acute and chronic bladder inflammation in transgenic experimental autoimmune cystitis models. J Biomed Biotechnol. 2011:937061. doi: 10.1155/2011/937061. Epub 2010 Nov 11. [PMID: 21113298] [PMC2989383]
Keywords: acute disease; autoimmune diseases; chronic disease; cystitis; dimethyl sulfoxide; dose-response relationship; epitopes; spleen/cytology; urinary bladder diseases.

2009

Evidence for overlap between urological and nonurological unexplained clinical conditions.

Rodríguez MÁ, Afari N, Buchwald DS. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol. 2009 Nov;182(5):2123-31. doi: 10.1016/j.juro.2009.07.036. Epub 2009 Sep 16. [PMID: 19758633] [PMC2957306]
Keywords: urogenital system; fatigue syndrome; chronic; fibromyalgia; irritable bowel syndrome; temporomandibular joint disorders.