Researchers at Fudan University have identified a biological "emotion gate" in the brain that influences whether chronic pain develops into clinical depression. This discovery may offer a new approach for individuals experiencing both physical and mental illness. The study was published in the journal Science.
Approximately 60 percent of individuals with chronic pain also experience depression. The research aimed to identify the biological mechanism linking these conditions.
The Hippocampus: An Emotion Gate
The research team, located at Fudan University's Institute of Science and Technology for Brain-inspired Intelligence, found this gate within the hippocampus. The hippocampus, known for its role in memory and navigation, also contributes significantly to mood regulation.
Analysis of neuroimaging data from 30,000 people and animal models indicated that the brain attempts to counteract pain initially. Xiao Xiao, a co-corresponding author and executive director at the institute, stated that the hippocampus temporarily enlarges and its functional state improves in the early stages of pain.
However, with persistent pain and the onset of depression, the hippocampus shows atrophy, leading to a decline in its regulatory capacity.
The specific sub-region identified as the gate is the dentate gyrus (DG). This area is capable of producing new neurons, a process known as plasticity, which aids the brain in adapting to stress.
How the Gate Fails
In the initial phases of pain, these new neurons exhibit high activity. As pain becomes chronic, microglia, the brain's immune cells, become overactive. This overactivity disrupts the balance of electrical signals in the brain, causing the "emotion gate" to fail and allowing physical pain to transition into a sustained negative emotional state.
A New Strategy for Intervention
This finding suggests a potential new strategy to prevent depression in pain patients. Instead of solely focusing on pain treatment, medical professionals could use brain imaging to monitor the hippocampus and intervene proactively.
While inhibiting new neurons prevented emotional decline, it resulted in cognitive side effects. Targeting the overactive microglia proved more effective.
Xiao mentioned that a clinically established drug used to regulate microglia was effective in their study and could potentially be adapted for patient use.
The researchers, who began this project in 2018, plan to use artificial intelligence to identify new small-molecule drugs targeting these specific brain cells. They propose that genetic and environmental factors likely influence the resilience of an individual's emotion gate.