title: Unique Microstructural Changes in the Brain Associated with Urological Chronic Pelvic Pain Syndrome (UCPPS) Revealed by Diffusion Tensor MRI, Super-Resolution Track Density Imaging, and Statistical Parameter Mapping: A MAPP Network Neuroimaging Study.
abstract: Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively. We hypothesized patients with UCPPS may have microstructural differences in the brain compared with healthy control subjects (HCs), as well as patients with irritable bowel syndrome (IBS), a common gastrointestinal pain disorder. In the current study we performed population-based voxel-wise DTI and super-resolution track density imaging (TDI) in a large, two-center sample of phenotyped patients from the multicenter cohort with UCPPS (N = 45), IBS (N = 39), and HCs (N = 56) as part of the MAPP Research Network. Compared with HCs, UCPPS patients had lower fractional anisotropy (FA), lower generalized anisotropy (GA), lower track density, and higher mean diffusivity (MD) in brain regions commonly associated with perception and integration of pain information. Results also showed significant differences in specific anatomical regions in UCPPS patients when compared with IBS patients, consistent with microstructural alterations specific to UCPPS. While IBS patients showed clear sex related differences in FA, MD, GA, and track density consistent with previous reports, few such differences were observed in UCPPS patients. Heat maps illustrating the correlation between specific regions of interest and various pain and urinary symptom scores showed clustering of significant associations along the cortico-basal ganglia-thalamic-cortical loop associated with pain integration, modulation, and perception. Together, results suggest patients with UCPPS have extensive microstructural differences within the brain, many specific to syndrome UCPPS versus IBS, that appear to be localized to regions associated with perception and integration of sensory information and pain modulation, and seem to be a consequence of longstanding pain.
authors.affiliation: Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Biomedical Physics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Davis
authors.initials: D
authors.lastname: Woodworth
authors.affiliation: Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Digestive Diseases and Gastroenterology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Emeran
authors.initials: E
authors.lastname: Mayer
authors.affiliation: Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Bioengineering, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Leu
authors.affiliation: Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Digestive Diseases and Gastroenterology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Cody
authors.initials: C
authors.lastname: Ashe-McNalley
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Naliboff
authors.affiliation: Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Digestive Diseases and Gastroenterology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Labus
authors.affiliation: Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Digestive Diseases and Gastroenterology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Tillisch
authors.affiliation: Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Kutch
authors.affiliation: Department of Physiology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Farmer
authors.affiliation: Department of Physiology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: A Vania
authors.initials: AV
authors.lastname: Apkarian
authors.affiliation: Department of Neurology, Stanford University, Palo Alto, California, United States of America.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Department of Neurology, Stanford University, Palo Alto, California, United States of America.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Mackey
authors.affiliation: Department of Anesthesiology, University of Alabama, Birmingham, Alabama, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ness
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Landis
authors.affiliation: Department of Radiology, University of Alabama, Birmingham, Alabama, United States of America.
authors.forename: Georg
authors.initials: G
authors.lastname: Deutsch
authors.affiliation: Department of Anestesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.affiliation: Department of Anestesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.affiliation: Division of Kidney, Urologic, and Hematologic Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Mullins
authors.affiliation: Department of Radiological Science, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Biomedical Physics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Oppenheimer Center for the Neurobiology of Stress, and PAIN, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Bioengineering, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D059350:Chronic Pain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000473:pathology; D008297:Male; D059906:Neuroimaging; D017699:Pelvic Pain / Q000473:pathology*; D012727:Sex Characteristics