Prolonged Pain Reshapes The Brain's Memory Centre, Influencing Depression Risk: Study

Changes to one's hippocampus, the brain's memory centre, in response to prolonged pain could be an important factor for why some people develop depression in chronic pain, while others do not, according to a study.

"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," co-lead author Jianfeng Feng, professor of computer science at the UK's University of Warwick, said.

The study, published in the journal Science, analysed brain scans from population cohorts, including data from the UK Biobank, and a rodent model.

People living with chronic pain but without depression tended to show a slightly larger volume of and an increased activity in the hippocampus.

The changes were accompanied by an improved performance in learning and memory tasks, suggesting that the brain may initially mount a compensatory response to persistent pain, the researchers said.

However, individuals experiencing both chronic pain and depression showed a reduced volume of the hippocampus, disrupted activity, and poorer cognitive performance.

Analyses of data collected over long-term indicated that the changes developed progressively over time.

"The fact that these changes emerge gradually suggests they are driven by the experience of prolonged pain itself. This isn't simply a pre-existing vulnerability; it's something the brain is doing in response to ongoing pain," Feng said.

The authors wrote, "Integrating human neuroimaging from the UK Biobank with a rodent model, we uncovered biphasic hippocampal remodelling." "Hippocampal volume increased during early pain stages, with paradoxical cognitive improvements, but declined with comorbid depression," they said.

Conducting parallel studies in animal models with chronic pain, the researchers found that an increased sensitivity to pain appeared first, followed by anxiety-like behaviour, and later by depression-like symptoms.

Structure and activity of the hippocampus gradually changed, showing how a prolonged pain can reshape brain circuits involved in emotional regulation, they said.

A key regulatory hub was found to be located in a sub-region of the hippocampus, known as the 'dentate gyrus' -- one of the few areas of an adult brain where new neurons continue to form.

Newly generated neurons in the dentate gyrus became highly active early in the course of chronic pain, suggesting the brain initially attempts to adapt to ongoing stress, the researchers said.

However, over time, immune cells in the brain called microglia became abnormally activated, with a disrupted communication between neurons and microglia marking a tipping point from adaptive processes to dysfunctional signalling, they said.

Suppressing the abnormal activity in the microglia was seen to improve depression-like behaviours, while overall brain function remained stable.

"What this shows is that the brain is not simply overwhelmed by chronic pain. It actively tries to regulate emotional wellbeing. When that regulatory system remains balanced, people can stay resilient," Feng said.

"When it becomes disrupted, particularly by inflammation in the hippocampus, depression can emerge. Understanding this process opens new possibilities for early intervention," the author said.

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