The lateral Habenula: Role in Chronic Pain and Depression

Abstract

Pain and depression share common neuroanatomical underpinnings, and the brain area affected by depression is also involved in the perception and processing of pain. The brain areas affected by both pain and depression include the insular cortex, medial prefrontal cortex, anterior cingulate cortex, hippocampus, habenula, amygdala, and thalamus [12-14]. The habenula is an evolutionarily ancient and centrally located nucleus that participates in a series of important biological processes [15]. The neural circuit composed of the habenula, periaqueductal gray, ventral tegmental area (VTA), and dorsal raphe nucleus (DRN) regulates norepinephrine (NE), serotonin (5-HT), dopamine (DA), and other neurotransmitter systems that are closely related to pain and depression [1618]. Recent studies have suggested that the activation of the habenula and the subsequent changes in neurotransmitter activity caused by chronic pain are an important explanation for the promotion of depression-like behavior, and the activation of the habenula might also be a key factor causing pain sensitivity under conditions of depression [19,20]. As a core brain region that transmits information from the forebrain limbic system to the midbrain monoaminergic and dopaminergic neurons, the habenula might be an important region in the pathogenesis of pain-depression comorbidity and might also serve as a therapeutic target. Thus, this article summarizes the structural and functional changes in the habenula in chronic pain and depression, both individually and together, and explores the mechanism of habenular involvement in pain-depression comorbidity. Introduction