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 J.
AU - Schaeffer, Anthony J.
AU - Apkarian, Apkar Vania
AU - Cella, David
AU - Farmer, Melissa A.
AU - Fitzgerald, Colleen
AU - Gershon, Richard
AU - Griffith, James W.
AU - Heckman, Charles J.
AU - Jiang, Mingchen
AU - Keefer, Laurie
AU - Marko, Darlene S.
AU - Michniewicz, Jean
AU - Parrish, Todd
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.
N1 - Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2018/12
Y1 - 2018/12
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.
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U2 - 10.1371/journal.pone.0206807
DO - 10.1371/journal.pone.0206807
M3 - Article
C2 - 30517112
AN - SCOPUS:85058082554
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 12
M1 - e0206807
ER -