Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS)

A MAPP network study

MAPP Research Network, MAPP Research Network Study Group

Research output: Contribution to journalArticle

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 (R 2 = 0.49, P<0.0001) and FA (R 2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R 2 = 0.42, P = 0.0001) and FA (R 2 = 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 (R 2 = 0.30, P = 0.002; R 2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R 2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R 2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R 2 = 0.35, P = 0.0006) and FA (R 2 = 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.

Original languageEnglish (US)
Article numbere0206807
JournalPloS one
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Pelvic Pain
Anisotropy
Chronic Pain
pain
Brain
diffusivity
urine
Urine
Diffusion tensor imaging
brain
Diffusion Tensor Imaging
Proteins
proteins
image analysis
brain stem
Vascular Endothelial Growth Factor A
Brain Stem
Neuroimaging
Neuronal Plasticity
Biomarkers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{f13dc3a1482a4d8a8c90d27b100744f7,
title = "Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS): A MAPP network study",
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 (R 2 = 0.49, P<0.0001) and FA (R 2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R 2 = 0.42, P = 0.0001) and FA (R 2 = 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 (R 2 = 0.30, P = 0.002; R 2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R 2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R 2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R 2 = 0.35, P = 0.0006) and FA (R 2 = 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.",
author = "{MAPP Research Network} and {MAPP Research Network Study Group} and Woodworth, {Davis C.} and Adelle Dagher and Adam Curatolo and Monisha Sachdev and Cody Ashe-McNalley and Naliboff, {Bruce D.} and Labus, {Jennifer S.} and Landis, {J. Richard} and Kutch, {Jason J.} and Mayer, {Emeran A.} and Lee, {Richard S.} and Moses, {Marsha A.} and Ellingson, {Benjamin M.} and Clemens, {J. Quentin} and Philip Hanno and Ziya Kirkali and Kusek, {John W.} and Lucia, {M. Scott} and Chris Mullins and Pontari, {Michel A.} and David Klumpp and Schaeffer, {Anthony J} and Apkar Apkarian and David Cella and Farmer, {Melissa A.} and Colleen Fitzgerald and Richard Gershon and Griffith, {James W} and Cj Heckman and Mingchen Jiang and Laurie Keefer and Marko, {Darlene S.} and Jean Michniewicz and Parrish, {Todd B} and Frank Tu and Rodriguez, {Larissa V.} and Jeffry Alger and Nuwanthi Heendeniya and Kilpatrick, {Lisa A.} and Fornessa Randal and Smith, {Suzanne R.} and Kreder, {Karl J.} and Bradley, {Catherine S.} and Mary Eno and Kris Greiner and Yi Luo and Lutgendorf, {Susan K.} and O’Donnell, {Michael A.} and Barbara Ziegler and Clauw, {Daniel J.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0206807",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

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

In: PloS one, Vol. 13, No. 12, e0206807, 01.12.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS)

T2 - A MAPP network study

AU - MAPP Research Network

AU - MAPP Research Network Study Group

AU - Woodworth, Davis C.

AU - Dagher, Adelle

AU - Curatolo, Adam

AU - Sachdev, Monisha

AU - Ashe-McNalley, Cody

AU - Naliboff, Bruce D.

AU - Labus, Jennifer S.

AU - Landis, J. Richard

AU - Kutch, Jason J.

AU - Mayer, Emeran A.

AU - Lee, Richard S.

AU - Moses, Marsha A.

AU - Ellingson, Benjamin M.

AU - Clemens, J. Quentin

AU - Hanno, Philip

AU - Kirkali, Ziya

AU - Kusek, John W.

AU - Lucia, M. Scott

AU - Mullins, Chris

AU - Pontari, Michel A.

AU - Klumpp, David

AU - Schaeffer, Anthony J

AU - Apkarian, Apkar

AU - Cella, David

AU - Farmer, Melissa A.

AU - Fitzgerald, Colleen

AU - Gershon, Richard

AU - Griffith, James W

AU - Heckman, Cj

AU - Jiang, Mingchen

AU - Keefer, Laurie

AU - Marko, Darlene S.

AU - Michniewicz, Jean

AU - Parrish, Todd B

AU - Tu, Frank

AU - Rodriguez, Larissa V.

AU - Alger, Jeffry

AU - Heendeniya, Nuwanthi

AU - Kilpatrick, Lisa A.

AU - Randal, Fornessa

AU - Smith, Suzanne R.

AU - Kreder, Karl J.

AU - Bradley, Catherine S.

AU - Eno, Mary

AU - Greiner, Kris

AU - Luo, Yi

AU - Lutgendorf, Susan K.

AU - O’Donnell, Michael A.

AU - Ziegler, Barbara

AU - Clauw, Daniel J.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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 (R 2 = 0.49, P<0.0001) and FA (R 2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R 2 = 0.42, P = 0.0001) and FA (R 2 = 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 (R 2 = 0.30, P = 0.002; R 2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R 2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R 2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R 2 = 0.35, P = 0.0006) and FA (R 2 = 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.

AB - 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 (R 2 = 0.49, P<0.0001) and FA (R 2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R 2 = 0.42, P = 0.0001) and FA (R 2 = 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 (R 2 = 0.30, P = 0.002; R 2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R 2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R 2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R 2 = 0.35, P = 0.0006) and FA (R 2 = 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.

UR - http://www.scopus.com/inward/record.url?scp=85058082554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058082554&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0206807

DO - 10.1371/journal.pone.0206807

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0206807

ER -