Research Links Chronic Pain to Depression Through Brain

Study finds hippocampus changes may explain why some chronic pain patients develop depression

Mar. 21, 2026 at 4:07am

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Researchers have found that chronic pain can lead to changes in the hippocampus region of the brain, which may explain why some chronic pain patients develop depression. The study analyzed brain scans from over 14,000 participants and found that those with chronic pain and depression showed reduced hippocampal volume and impaired cognitive performance compared to those with chronic pain alone. Animal studies also showed similar patterns, with the dentate gyrus region of the hippocampus emerging as a critical factor in the transition from chronic pain to depression.

Why it matters

This discovery helps explain the long-observed link between chronic pain and depression, and points to potential treatments that could prevent depression from developing in chronic pain patients. Understanding the brain's coping mechanisms in response to chronic stress may also apply to other conditions beyond just chronic pain.

The details

The researchers analyzed brain scans from 14,462 participants in the UK Biobank cohort, comparing those with chronic pain for at least 7 years who did not have depression, to those who developed depressive symptoms either throughout the 7-year period or after 2 or 4 years. They found that those with both chronic pain and depression showed reduced hippocampal volume and impaired cognitive performance, while those with chronic pain alone exhibited modest increases in hippocampal volume and improved memory. Animal studies corroborated these findings, showing that the dentate gyrus region of the hippocampus was a critical factor, with initial protective responses giving way to abnormal microglial activation that disrupted normal neural signaling.

  • The study analyzed brain scans from participants over a 7-year period.
  • The depressive symptoms in some participants developed either throughout the 7-year period or after 2 or 4 years.

The players

Barbara Jacquelyn Sahakian

Professor of Clinical Neuropsychology at the University of Cambridge.

Jianfeng Feng

Professor of Science and Technology for Brain-Inspired Intelligence/Computer Science at Fudan University.

Trevor Robbins

Professor of Neuroscience at the University of Cambridge.

Xiao Xiao

Associate Professor at the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University.

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What they’re saying

“Chronic pain has long been known to be associated with depression.”

— Barbara Jacquelyn Sahakian, Professor of Clinical Neuropsychology, University of Cambridge

What’s next

The researchers suggest that a treatment like the antibiotic minocycline, which suppressed abnormal microglial activation and reduced depression-like behavior in animal models, could help prevent depression in people living with persistent pain if introduced early.

The takeaway

This study provides important insights into the brain mechanisms linking chronic pain and depression, and points to potential interventions that could help prevent depression from developing in chronic pain patients, as well as having broader implications for understanding the brain's response to chronic stress.