The nose-brain axis as a neuroimmune conduit: how allergic rhinitis rewires the central nervous system

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.