Research from the UK and China found that progressive changes in a key brain region may explain why some people with chronic pain develop depression while others remain emotionally resilient. 

Chronic pain affects more than 20% of adults worldwide and is strongly linked to anxiety and depression. However, many people living with chronic pain never develop these mental health conditions, and the reasons behind it remain unknown. 

Researchers from the University of Warwick and Fudan University combined large-scale human brain imaging with experiments in rats with chronic pain. They focused on the hippocampus, a brain region involved in memory and emotional regulation and where new brain cells are produced.  

In humans and rats, the team found that in early stages of chronic pain, the hippocampus grew slightly, mental performance improved and the brain initially coped. However, as pain continued, the hippocampus shrank, cognition declined and depression- and anxiety-like behaviours emerged.  

They found that microglia, brain immune cells, were abnormally activated, and disrupted the balance of activity in the hippocampus region. Suppressing this abnormal activity successfully prevented depression-like behaviours in rats without affecting cognitive function. 

Jianfeng Feng, from the University of Warwick and co-lead author of the study, said, “Our findings suggest that the hippocampus acts as a control centre that helps the brain regulate emotional responses to long-term pain. Depression is not inevitable — it depends on how this system responds over time." 

These results, published in Science, point to possible avenues of using the hippocampus as a target for new approaches to treat depression associated with chronic pain.