Stress-Related Brain Alterations in Chronic Pain

Stress symptoms are commonly experienced by people with chronic pain. Although stress and chronic pain are associated with similar effects on brain morphology, the present study aims to clarify the relationship between stress severity, chronic pain, and brain morphology.

Fifty-two people with chronic pain and 38 pain-free healthy controls (HC) underwent T1-weighted magnetic resonance imaging. Severity of stress symptoms was measured using the civilian version of the posttraumatic stress disorder checklist (PCL-C). A series of multiple linear regressions determined the main effects of group, stress symptom severity (PCL-C total score and symptom-specific scores) and their interaction on grey matter volume of selected regions of interest.

The interaction term was significantly associated with variations in grey matter volume in the left and right putamen, the left middle cingulate cortex (MCC) and the right posterior insula. Results showed significantly smaller left and right putamen when reporting higher stress levels, and significantly larger left MCC and right posterior insula at lower stress levels in people with chronic pain compared to HCs. In addition, increasing stress severity was significantly associated with larger left and right putamen in HCs, and significantly associated with smaller left MCC and right posterior insula in people with chronic pain.

Severity of stress moderated chronic pain-related grey matter alterations. More severe stress, especially avoidance, was associated with smaller left MCC, a core region of the "pain matrix". The MCC is strongly linked with the somatosensory network and critical for empathy, especially toward pain-related stimuli.

To our knowledge, this is the first study to show that stress severity differentially impacts grey matter integrity in people with chronic pain compared to pain-free healthy controls. Briefly, our results indicate that higher levels of stress were associated with larger putamen and right posterior insula in pain-free participants, potentially reflecting mechanisms of resilience to trauma in this group. Higher levels of stress, especially avoidance symptoms, were associated with smaller left middle cingulate cortex, a region with strong links to the somatosensory network and critical for empathy, especially toward pain-related stimuli.