657: Severity and timing of trauma exposure and chronic pain alter white matter integrity in older adults

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Psychology, Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Lifetime exposure to trauma increases the risk and persistence of chronic pain later in life. Evidence for alterations in white matter integrity has been associated with disrupted communication among sensory, affective, and pain-regulatory systems in separate studies of chronic pain and trauma. Despite the high comorbidity between trauma and chronic pain in older adults, the combined effects of trauma exposure and chronic pain on white matter integrity remain unclear. This study aimed to examine the effects of trauma exposure at different neurodevelopmental periods (childhood, adulthood, and both) on white matter microstructure integrity in older adults experiencing chronic pain.

Methods: Older adults from the UK Biobank (N = 21,996; 13,249 controls, 8,747 chronic pain) with minimally pre-processed white matter metrics (fractional anisotropy [FA] and mean diffusivity [MD]) across 48 tracts defined by the Johns Hopkins University atlas were included [1]. Chronic pain was defined as pain persisting for ≥3 months, and trauma exposure was assessed via self-report questionnaires. Linear mixed-effects models examined main effects of group, trauma severity (separately for childhood maltreatment only, adulthood trauma only, and both), and their interactions on FA and MD. False discovery rate correction was applied, and effect sizes (Cohen’s d, standardised beta) were computed.

Results: Chronic pain, when accounting for trauma severity, was significantly associated with lower FA and MD in brainstem tracts and cingulum, and greater MD in the superior fronto-occipital fasciculus. Severity of exposure to both childhood and adulthood trauma was associated with widespread FA reductions, greater MD in frontal and parietal tracts, and lower MD in brainstem tracts. Adulthood trauma showed similar but attenuated patterns, whereas the severity of childhood maltreatment showed localised FA and MD reductions in the brainstem tracts, sagittal stratum, and superior longitudinal fasciculus. Group-by-trauma-severity interactions were not significantly associated with variation in any of the tracts studied.

Conclusions: Distinct, but not additive, effects of chronic pain and trauma on white matter microstructure were evident in adults from the UK Biobank. The observed dose-response relationship between trauma severity and white matter microstructure is consistent with mechanisms of allostatic overload and cumulative burden of chronic stress on brain integrity. Recency effects, where severity of adulthood trauma alone has more pronounced effects than childhood maltreatment alone, may reflect resilient reorganisation processes that normalise/minimise long-term effects of childhood maltreatment. These findings highlight the importance of accounting for lifetime trauma exposure when examining white matter alterations in this population.

References: [1] Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JLR, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SM. Multimodal population brain imaging in the UK Biobank prospective epidemiological study. Nat Neurosci 2016;19:1523–1536.

Presenting Author: Tong En Lim
Submitting Author: Tong En Lim

Senior Author: Yann Quidé

IASP 2026 Global Year theme of Neuropathic Pain: No

• Sylvia M. Gustin: PhD - UNSW Sydney
• Yann Quidé: PhD - UNSW Sydney