肺–脑轴神经环路在慢性咳嗽中的作用及干预策略研究进展

Research Progress on the Role and Intervention of Lung-Brain Axis Neural Circuit in Chronic Cough

摘要: 慢性咳嗽是影响全球约10%人群的常见症状，其认知已从单纯气道保护性反射，拓展为肺–脑轴双向调控的复杂过程——外周迷走神经传入信号经脑干至高位脑区完成多级整合，是其发病的核心机制。本文聚焦肺–脑轴神经环路在慢性咳嗽中的作用及干预策略：该调控网络涵盖多个关键靶点，外周感觉神经元特定亚群为信号初始感受器，脑干咳嗽中枢负责中继整合，高位脑区参与高级调控；而神经突触可塑性改变、神经炎症介导的中枢敏化，是慢性咳嗽持续高敏的核心病理基础。新型P2X3受体调节剂可阻断外周神经信号，神经调节剂能纠正中枢敏化，中医药兼具抗炎与神经调节的协同效应；咳嗽技能训练、神经反馈技术等非药物疗法，也可通过调节脑区活动改善咳嗽高反应性，均展现出临床应用潜力。综上，肺–脑轴的多级调控机制为慢性咳嗽精准治疗提供了理论支撑，未来需聚焦多模式、个体化干预方案的临床研究，以推动转化应用。

Abstract: Chronic cough is a common symptom affecting approximately 10% of the global population. Its understanding has evolved from being merely considered a protective reflex of the airways to a complex process involving bidirectional regulation along the lung-brain axis. The core pathogenic mechanism involves multilevel integration of peripheral vagal afferent signals, which are relayed through the brainstem to higher brain regions. This article focuses on the role of neural circuits of the lung-brain axis in chronic cough and potential intervention strategies. This regulatory network encompasses several key targets: specific subpopulations of peripheral sensory neurons act as initial signal receptors, the brainstem cough center is responsible for relay and integration, and higher brain regions participate in advanced modulation. Furthermore, alterations in synaptic plasticity and neuroinflammation-mediated central sensitization constitute the core pathological basis for persistent hypersensitivity in chronic cough. Novel P2X3 receptor modulators can block peripheral nerve signals, neuromodulators can correct central sensitization, and traditional Chinese medicine has synergistic effects of anti-inflammation and neural modulation; non-pharmacological therapies such as cough skill training and neurofeedback techniques can also improve cough hyperreactivity by modulating brain activity, showing clinical potential. In summary, the multi-level regulatory mechanisms of the lung-brain axis provide a theoretical basis for precise treatment of chronic cough. Future research should focus on clinical studies of multi-modal, individualized intervention strategies to promote translational applications.