Featured Publications
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. Pain. 2024 Nov 5. doi: 10.1097/j.pain.0000000000003455. Online ahead of print. [PMID: 39499552] [PMC – ePub]
Abstract
Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.
Keywords: Pelvic pain; Widespread pain; Reanalysis of clinical trial results; Pain measurement; Interstitial cystitis
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.
Brain predicted age in chronic pelvic pain: a study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.
Leech KA, Kettlety SA, Mack WJ, Kreder KJ, Schrepf A, Kutch JJ. Pain. 2024 Oct 16. doi: 10.1097/j.pain.0000000000003424. Online ahead of print. Epub 2024 Jan 22. [PMID: 39432808] [ePub]
Abstract
The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted - chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average-however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.
Keywords: Chronic pain; Pelvic pain; Brain age; Structural MRI; Inflammation
Trial registration: ClinicalTrials.gov NCT02514265.
Copyright © 2024 International Association for the Study of Pain.
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
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.
© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.
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
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
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.
© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.
