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

Davis C Woodworth; Adelle Dagher; Adam Curatolo; Monisha Sachdev; Cody Ashe-McNalley; Bruce D Naliboff; Jennifer S Labus; J Richard Landis; Jason J Kutch; Emeran A Mayer; Richard S Lee; Marsha A Moses; Benjamin M Ellingson; MAPP Research Network

doi:10.1371/journal.pone.0206807

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

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

Davis C Woodworth, Adelle Dagher, Adam Curatolo, Monisha Sachdev, Cody Ashe-McNalley, Bruce D Naliboff, Jennifer S Labus, J Richard Landis, Jason J Kutch, Emeran A Mayer, …

PloS one, Vol.13(12), pp.e0206807-e0206807

2018

DOI: 10.1371/journal.pone.0206807

PMCID: PMC6281196

PMID: 30517112

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Abstract

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network has yielded neuroimaging and urinary biomarker findings that highlight unique alterations in brain structure and in urinary proteins related to tissue remodeling and vascular structure in patients with Urological Chronic Pelvic Pain Syndrome (UCPPS). We hypothesized that localized changes in diffusion tensor imaging (DTI) measurements might be associated with corresponding changes in urinary protein levels in UCPPS. To test this hypothesis, we created statistical parameter maps depicting the linear correlation between DTI measurements (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) and urinary protein quantification (MMP2, MMP9, NGAL, MMP9/NGAL complex, and VEGF) in 30 UCPPS patients from the MAPP Research Network, after accounting for clinical covariates. Results identified a brainstem region that showed a strong correlation between both ADC (R2 = 0.49, P<0.0001) and FA (R2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R2 = 0.42, P = 0.0001) and FA (R2 = 0.29, P = 0.0020) and urinary MMP9/NGAL complex. Results also identified significant correlations between FA and urinary MMP9 in white matter adjacent to sensorimotor regions (R2 = 0.30, P = 0.002; R2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R2 = 0.35, P = 0.0006) and FA (R2 = 0.43, P<0.0001) with urinary NGAL levels. In contrast, no significant association between DTI measurements and VEGF was observed. Results suggest that elevated MMP9 or MMP9/NGAL in UCPPS may be related to degenerative neuronal changes in brainstem nuclei through excitotoxicity, while also facilitating synaptic plasticity in sensorimotor regions.

Lipocalin-2 - urine

Pelvic Pain - urine

Humans

Middle Aged

Brain Stem - diagnostic imaging

Male

Sensorimotor Cortex - diagnostic imaging

Syndrome

Diffusion Tensor Imaging

White Matter - diagnostic imaging

Chronic Pain - urine

Matrix Metalloproteinase 9 - urine

Pelvic Pain - diagnostic imaging

Proteinuria - urine

Adult

Female

Chronic Pain - diagnostic imaging

Proteinuria - diagnostic imaging

Details

Title: Subtitle: Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS): A MAPP Network study
Creators: Davis C Woodworth - G. Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
Adelle Dagher - Vascular Biology Program, Boston Children's Hospital, Boston, MA
Adam Curatolo - Vascular Biology Program, Boston Children's Hospital, Boston, MA
Monisha Sachdev - Vascular Biology Program, Boston Children's Hospital, Boston, MA
Cody Ashe-McNalley - Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
Bruce D Naliboff - Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
Jennifer S Labus - Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
J Richard Landis - Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America
Jason J Kutch - Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States of America
Emeran A Mayer - Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
Richard S Lee - Department of Surgery, Harvard Medical School, Boston, MA
Marsha A Moses - Department of Surgery, Boston Children's Hospital, Boston, MA
Benjamin M Ellingson - Department of Bioengineering, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America
MAPP Research Network
Contributors: Yi Luo (Contributor) - University of Iowa, Urology
Resource Type: Journal article
Publication Details: PloS one, Vol.13(12), pp.e0206807-e0206807
DOI: 10.1371/journal.pone.0206807
PMID: 30517112
PMCID: PMC6281196
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: U01 DK103227 / NIDDK NIH HHS R01 DK048351 / NIDDK NIH HHS U01 DK082325 / NIDDK NIH HHS
Language: English
Date published: 2018
Academic Unit: Urology
Record Identifier: 9984051509002771

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