Brain Switch in the Hippocampus Dictates Pain-Related Depression Risk

Large-scale brain imaging and animal studies show chronic pain gradually reshapes the hippocampus; early adaptations (larger volume and higher activity) correlate with resilience, while later changes include reduced hippocampal volume, disrupted activity, and cognitive decline that accompany depression. A dentate gyrus–microglia interaction appears to be a key switch from adaptive to maladaptive responses, and reducing hippocampal inflammation in animals improved depression-like symptoms, suggesting early anti-inflammatory treatment could help prevent pain-induced depression.