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PLoS One. 2018 Dec 5;13(12):e0206807. doi: 10.1371/journal.pone.0206807. eCollection 2018.

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

Author information

1
Department of Radiological Science, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America.
2
Department of Biomedical Physics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America.
3
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.
4
Vascular Biology Program, Boston Children's Hospital, Boston, MA.
5
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.
6
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America.
7
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America.
8
Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States of America.
9
Department of Urology, Boston Children's Hospital, Boston, MA.
10
Department of Surgery, Harvard Medical School, Boston, MA.
11
Department of Surgery, Boston Children's Hospital, Boston, MA.
12
Department of Bioengineering, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States of America.

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.

PMID:
30517112
PMCID:
PMC6281196
DOI:
10.1371/journal.pone.0206807
[Indexed for MEDLINE]
Free PMC Article

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