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^DRN) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOM^CeA neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HT^DRN→SOM^CeA 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^DRN→SOM^CeA→lateral habenula pathway may mediate at least some aspects of CDS.

慢性疼痛中并存的抑郁症状（CDS）是常见的健康问题，但这些症状背后的神经回路机制仍不清楚。在这里，我们确定了一条新途径，涉及从背phe核（5-HT ^DRN）到杏仁核（CeA）中央核中表达生长抑素（SOM）和非SOM中间神经元的5-羟色胺（5-HT）投影。SOM ^CeA神经元直接投射到外侧^{哈贝努拉（}已知与抑郁有关的区域）。5-HT ^DRN →SOM ^CeA的抑制该途径在慢性疼痛的雄性小鼠模型中产生了抑郁样行为。使用药理或光遗传学方法激活该途径可减少这些小鼠的抑郁样行为。人类功能磁共振成像数据显示，与健康对照相比，患有CDS的患者中含CeA的中央杏仁核与DRN之间的功能连接性降低，而患有慢性抑郁症且无抑郁的患者则没有这种连接性。这些发现表明，新颖的5-HT ^DRN →SOM ^CeA →侧^ha通路可以介导CDS的至少某些方面。