Involvement of the hippocampus in chronic pain and depression

Increases in depressive behaviors have been reported in patients experiencing chronic pain. In these patients, the symptoms of pain and depression commonly coexist, impairing their lives and challenging effective treatment. The hippocampus may play a role in both chronic pain and depression. A reduction in the volume of the hippocampus is related to reduced neurogenesis and neuroplasticity in cases of chronic pain and depression. Moreover, an increase of proinflammatory factors and a reduction of neurotrophic factors have been reported to modulate the hippocampal neurogenesis and neuroplasticity in chronic pain and depression. This review discusses the mechanisms underlying the depressive-like behavior accompanying chronic pain, emphasizing the structural and functional changes in the hippocampus. We also discuss the hypothesis that pro-inflammatory factors and neurotrophic factors expressed in the hippocampus may serve as a therapeutic target for comorbid chronic pain and depression.