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Nat Neurosci. 2019 Oct;22(10):1649-1658. doi: 10.1038/s41593-019-0468-2. Epub 2019 Aug 26.

A neural circuit for comorbid depressive symptoms in chronic pain.

Author information

1
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, China.
2
Department of Neurology, Department of Anesthesiology and Department of Pain Management, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
3
Department of Psychology, Anhui Mental Health Center, Hefei, China.
4
Key Laboratory of Animal Models and Human Disease Mechanisms, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
5
State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
6
Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
7
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
8
Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
9
Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, China. zhizhang@ustc.edu.cn.

Abstract

Comorbid depressive symptoms (CDS) in chronic pain are a common health problem, but the neural circuit mechanisms underlying these symptoms remain unclear. Here we identify a novel pathway involving 5-hydroxytryptamine (5-HT) projections from the dorsal raphe nucleus (5-HTDRN) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOMCeA neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HTDRN→SOMCeA pathway produced depression-like behavior in a male mouse model of chronic pain. Activation of this pathway using pharmacological or optogenetic approaches reduced depression-like behavior in these mice. Human functional magnetic resonance imaging data showed that compared to healthy controls, functional connectivity between the CeA-containing centromedial amygdala and the DRN was reduced in patients with CDS but not in patients in chronic pain without depression. These findings indicate that a novel 5-HTDRN→SOMCeA→lateral habenula pathway may mediate at least some aspects of CDS.

PMID:
31451801
DOI:
10.1038/s41593-019-0468-2

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