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.
Department of Neurology, Department of Anesthesiology and Department of Pain Management, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Nat Neurosci. 2019 Oct;22(10):1649-1658. doi: 10.1038/s41593-019-0468-2. Epub 2019 Aug 26.
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-HT) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOM neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HT→SOM 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-HT→SOM→lateral habenula pathway may mediate at least some aspects of CDS.
慢性疼痛合并抑郁症状（CDS）是一种常见的健康问题，但这些症状的神经回路机制仍不清楚。在这里，我们确定了一条涉及 5-羟色胺（5-HT）从背侧中缝核（DRN）投射到杏仁中央核（CeA）中生长抑素（SOM）表达和非-SOM 中间神经元的新途径。SOM 神经元直接投射到外侧缰核，该区域已知与抑郁有关。在慢性疼痛的雄性小鼠模型中，抑制 5-HT→SOM 通路会产生类似抑郁的行为。使用药理学或光遗传学方法激活该通路可减少这些小鼠的类似抑郁的行为。人类功能磁共振成像数据显示，与健康对照组相比，患有 CDS 的患者的 CeA 包含的中央杏仁核与 DRN 之间的功能连接减少，但患有无抑郁的慢性疼痛的患者则没有。这些发现表明，一种新的 5-HT→SOM→外侧缰核通路可能至少介导了 CDS 的某些方面。
