Chronic pain is associated with anxio-depressive comorbidities, but the neuroanatomical substrates remain unknown. A specific serotonergic pathway from the dorsal raphe nucleus to the lateral habenula via the central amygdala is now uncovered as a key neural circuit governing comorbid depressive symptoms in chronic pain.

Specifically, the authors identified a novel pathway involving 5-hydroxytryptamine projections from the dorsal raphe nucleus to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala. The SOM neurons in the amygdala projected directly to the lateral habenula, an area known to be involved in depression. Manipulation of this pathway using pharmacological or optogenetic approaches modulated depression-like behavior in laboratory animals.

Zhou W, Jin Y, Meng Q, Zhu X, Bai T, Tian Y, Mao Y, Wang L, Xie W, Zhong H, Zhang N, Luo MH, Tao W, Wang H, Li J, Li J, Qiu BS, Zhou JN, Li X, Xu H, Wang K, Zhang X, Liu Y, Levin GR, Xu L and Zhang Z: A neural circuit for comorbid depressive symptoms in chronic pain. Nature Neurosci. 22(10): 1649-1658 (2019).

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