Overview
- Analyses of large cohorts, including UK Biobank, found people with chronic pain but no depression had slightly larger, more active hippocampi and better cognitive performance.
- Those with both chronic pain and depression showed reduced hippocampal volume, disrupted activity, and poorer cognition in patterns that unfolded progressively over time.
- Longitudinal evidence supports a pain-driven remodeling process rather than a purely pre-existing vulnerability.
- In rodent models, heightened pain sensitivity preceded anxiety-like behavior and then depression-like symptoms, paralleling gradual hippocampal changes.
- Suppressing abnormal microglial activation in animals improved depression-like behaviors, suggesting a potential early-intervention target that remains preclinical.