Pain, But Not Physical Activity, Is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic...

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWVs), yet the causes are poorly understood. Brain structure abnormalities are observed in GWVs, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWVs with and without CMP. Ninety-eight GWVs (10 females) with CMP and 56 GWVs (7 females) controls completed T1-weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance (ANCOVA). Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Familywise cluster error rates were used to control for multiple comparisons (α = 0.05). GWVs with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWVs (all p values < 0.05). GWVs with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p < 0.05_adjusted). Gray matter volumes in the left insula were associated with pain symptoms (r _partial = 0.26, -0.29; p < 0.05_adjusted). No significant associations were observed for either PA or sedentary time (p > 0.05_adjusted). GWVs with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing, which may reflect pain chronification.SIGNIFICANCE STATEMENT The pathophysiology of chronic pain in Gulf War veterans is understudied and not well understood. In a large sample of Gulf War veterans, we report veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared with otherwise healthy Gulf War veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.