鼻-脑轴作为神经免疫通道：过敏性鼻炎如何重塑中枢神经系统

文献信息

中文摘要

背景： 过敏性鼻炎（AR）传统上被视为局限于鼻黏膜的I型超敏反应性疾病。然而，持续存在的症状、鼻高反应性以及共病的神经精神障碍——包括头痛、疲劳、认知障碍（“脑雾”）、焦虑和抑郁——无法仅用外周炎症完全解释，从而提示中枢敏化的参与。鼻-脑轴作为关键的双向通道，将外周炎症信号传递至中枢神经系统（CNS）并启动神经免疫交互对话，目前这被认为是AR中枢敏化的核心驱动因素。方法：在本综述中，我们系统阐述鼻-脑轴介导AR中枢敏化的层级机制，包括：外周神经免疫突触形成、三叉神经传入信号、脑干和丘脑内的中枢整合、边缘系统和感觉皮层区域的功能重塑、小胶质细胞和星形胶质细胞活化、中枢细胞因子网络失调、谷氨酸能过度兴奋以及下行调制失衡。结果：我们进一步总结了针对鼻-脑轴的新兴治疗策略，包括外周神经调制、抑制中枢神经炎症、恢复神经递质稳态以及心理行为干预。结论：本综述为理解AR中的神经炎症和中枢敏化提供了统一的机制框架，并为开发针对难治性AR及中枢共病患者的靶向治疗提供了新见解。

英文摘要

Allergic rhinitis (AR) has traditionally been regarded as a type I hypersensitivity disorder confined to the nasal mucosa. However, persistent symptoms, nasal hyperresponsiveness, and comorbid neuropsychiatric disturbances-including headache, fatigue, cognitive impairment ("brain fog"), anxiety, and depression-cannot be fully explained by peripheral inflammation alone, thereby implicating the involvement of central sensitization. The nose-brain axis serves as a critical bidirectional conduit that relays peripheral inflammatory signals to the central nervous system (CNS) and initiates neuroimmune crosstalk, which is now recognized as a core driver of central sensitization in AR. In this review, we systematically delineate the hierarchical mechanisms by which the nose-brain axis mediates central sensitization in AR, encompassing: peripheral neuroimmune synapse formation, trigeminal afferent signaling, central integration within the brainstem and thalamus, functional remodeling of limbic and sensory cortical regions, microglial and astrocytic activation, central cytokine network dysregulation, glutamatergic hyperexcitation, and descending modulatory imbalance. We further summarize emerging therapeutic strategies targeting the nose-brain axis, including peripheral nerve modulation, suppression of central neuroinflammation, restoration of neurotransmitter homeostasis, and psychobehavioral interventions. This review provides a unified mechanistic framework for understanding neuroinflammation and central sensitization in AR and offers novel insights for developing targeted therapies for patients with refractory AR and central comorbidities.