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Cerebral white matter structure is disrupted in Gulf War Veterans with chronic musculoskeletal pain

Van Riper, Stephanie M.a,b; Alexander, Andrew L.c; Koltyn, Kelli F.b; Stegner, Aaron J.a,b; Ellingson, Laura D.d; Destiche, Daniel J.c; Dougherty, Ryan J.b; Lindheimer, Jacob B.a,b,e; Cook, Dane B.a,b,*

doi: 10.1097/j.pain.0000000000001038
Research Paper

Chronic musculoskeletal pain (CMP) affects ∼25% of the 700,000 Veterans deployed during the Persian Gulf War (1990-1991). The cause of their pain is unknown, and there are no efficacious treatments. A small body of literature suggests that brain abnormalities exist in Gulf War Veterans (GVs), yet relationships between brain abnormalities and disease symptoms remain largely unexplored. Our purpose was to compare white matter (WM) integrity between GVCMP and matched, healthy Veteran controls (GVCO) and investigate relationships between cerebral WM integrity and symptoms. Thirty GVCMP and 31 controls completed magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics estimated WM fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity over the whole brain (P < 0.05) and were corrected using threshold-free cluster enhancement. GVCMP had greater pain symptoms and mood disturbance and lower quality of life and physical function compared with GVCO (P < 0.05). GVCMP had lower WM integrity across several brain regions implicated in chronic pain (P < 0.05) including the middle and inferior frontal gyrus, corpus callosum, corona radiata, precentral gyrus, external capsule, and posterior thalamic radiation. For GVCMP, WM integrity was associated with pain and mood symptoms in widespread brain areas that were found to be different between groups (P < 0.05). Results indicate widespread WM microstructure disruption across brain regions implicated in pain processing and modulation in chronic pain. The observed relationships between WM microstructure and symptoms encourage the testing of treatments designed to improve the brain health of affected Veterans.

Supplemental Digital Content is Available in the Text.Widespread disruption of cerebral white matter microstructure across brain regions implicated in pain regulation was observed in Gulf War Veterans suffering from chronic pain.

aDepartment of Veterans Affairs, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

bDepartment of Kinesiology, University of Wisconsin—Madison, Madison, WI, USA

cWaisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin—Madison, Madison, WI, USA

dDepartment of Kinesiology, Iowa State University, Ames, IA, USA

eDepartment of Veterans Affairs, War Related Illness and Injury Study Center, New Jersey Healthcare System, East Orange, NJ, USA

Corresponding author. Address: Department of Kinesiology, University of Wisconsin—Madison, 2000 Observatory Drive, Madison WI 53706, USA. Tel.: 608-262-7737. E-mail address: (D. B. Cook).

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 (

Received March 10, 2017

Received in revised form July 21, 2017

Accepted August 03, 2017

© 2017 International Association for the Study of Pain
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