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Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case–control study

Huang, Lejian; Kutch, Jason J.; Ellingson, Benjamin M.; Martucci, Katherine T.; Harris, Richard E.; Clauw, Daniel J.; Mackey, Sean; Mayer, Emeran A.; Schaeffer, Anthony J.; Apkarian, A. Vania; Farmer, Melissa A.

doi: 10.1097/j.pain.0000000000000703
Research Paper

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

Supplemental Digital Content is Available in the Text.Women and men with chronic urological pelvic pain exhibit regional white matter changes in proportion to symptom severity that may aid phenotyping of urological pain.

aDepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

bDivision of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA

cOppenheimer Center for Neurobiology of Stress and Pain, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA

dDepartments of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University Medical Center, Stanford, CA, USA

eDepartment of Anesthesiology, and the Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA

fDepartment of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

gDepartments of Surgery and Anesthesia, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

Corresponding author. Address: Department of Physiology, Feinberg School of Medicine Northwestern University, 310 E. Superior St, Tarry 7-705, Chicago, IL 60611, USA. Tel.: (312) 503-0404. E-mail address: (M.A. Farmer).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Members of the MAPP Research Network members can be found in Ref. 15.

Received August 14, 2015

Received in revised form January 14, 2016

Accepted August 18, 2016

© 2016 International Association for the Study of Pain
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