Stress-related white matter microstructure alterations and chronic pain

Brain Imaging Behav. 2026 Feb 7;20(1):6. doi: 10.1007/s11682-026-01102-4.

ABSTRACT

Posttraumatic stress symptoms (PTSS) are commonly experienced in people with chronic pain. Reduced white matter microstructural integrity in the uncinate fasciculus and the cingulum has separately been reported in chronic pain and posttraumatic stress disorder (PTSD) studies. However, the relationship between chronic pain, PTSS and white matter integrity remains unclear. This study aims to disentangle the relationship between PTSS severity and white matter microstructural integrity common across different chronic pain conditions. Thirty-six subjects with chronic pain and 20 without chronic pain (controls) underwent diffusion weighted imaging and completed the civilian version of the PTSD CheckList (PCL-C). Average fractional anisotropy (FA) values were extracted from the uncinate fasciculus, and the cingulate and hippocampal portions of the cingulum. A series of multiple linear regressions determined the main effects of group, PTSS severity (PCL-C total score) and their interactions on each region separately. The group-by-PTSS interaction was significantly associated with uncinate fasciculus FA variations. Moderation analysis indicated that increasing PTSS severity was significantly associated with reduced uncinate fasciculus FA in the control group, but not in the chronic pain group. No other significant association was found for any other ROI FA values. Consistent with previous studies, increasing PTSS levels were associated with reduced FA of the uncinate fasciculus in controls, but not in people with chronic pain. Other mechanisms may be at play in chronic pain, including the interplay with other psychopathological problems or specific pain type effects.

PMID:41653339 | DOI:10.1007/s11682-026-01102-4