抑郁与慢性疼痛共病的神经机制研究

A Study on the Neural Mechanisms of Comorbid Depression and Chronic Pain

摘要: 抑郁症与慢性疼痛共病率极高且存在双向因果关联，其背后存在深刻的神经机制重叠。结构影像学显示，前扣带皮层、岛叶、前额叶及海马等脑区存在共同灰质萎缩。在环路水平，前扣带皮层作为疼痛–情绪整合枢纽，其与伏隔核、杏仁核的异常投射将疼痛信号转化为负性情绪；奖赏环路功能抑制导致快感缺失。大规模脑网络呈现默认模式网络过度连接、突显网络过度警觉及中央执行网络功能低下的三网络重构模式。分子机制涉及5-羟色胺/去甲肾上腺素功能低下、谷氨酸-GABA失衡及神经炎症通过小胶质细胞和色氨酸–犬尿氨酸通路介导的可塑性改变。临床治疗应靶向这些重叠节点，包括SNRIs药物、重复经颅磁刺激及认知行为疗法，并强调早期干预以阻断疼痛慢性化及抑郁发生。未来方向包括环路特异性调控、生物型分类及多模态纵向追踪。本文为理解抑郁–疼痛共病的神经基础及整合治疗提供理论依据。

Abstract: The comorbidity rate of depression and chronic pain is extremely high and there is a bidirectional causal association between depression and chronic pain, and there are profound overlapping neural mechanisms behind them. Structural imaging showed common gray matter atrophy in the anterior cingulate cortex, insular lobe, prefrontal lobe, and hippocampus. At the loop level, as the hub of pain-emotion integration, the Anterior Cingulate Cortex (ACC) has abnormal projections with nucleus accumbens and amygdala, which transform pain signals into negative emotions. Functional inhibition of the reward loop results in anhedonia. The large-scale brain network showed a three-network reconstruction pattern of default mode network overconnectivity, salience network overvigilance, and central executive network dysfunction. The molecular mechanism involves 5-HT/norepinephrine hypofunction, glutamate-GABA imbalance, and neuroinflammation-mediated plasticity changes through microglia and tryptophan-kynurenine pathways. Clinical treatment should target these overlapping nodes, including SNRIs drugs, repetitive transcranial magnetic stimulation and cognitive behavioral therapy, and emphasize early intervention to block the development of chronic pain and depression. Future directions include loop-specific regulation, biotype classification, and multimodal longitudinal tracking. This article provides a theoretical basis for understanding the neural basis and integrated treatment of depression-pain comorbidity.