The sneezing reflex: neurophysiology, neuroimmune pathways and clinical disorders

To review the physiological mechanisms, neural and molecular mediators, and clinical pathologies associated with the sneezing reflex.

A comprehensive narrative review was conducted utilizing established databases (PubMed/Medline, Scopus, Web of Science, Embase), covering articles published up to 2025. A structured search strategy applied keywords such as "sneezing reflex," "neuromedin B (NMB)," "trigeminal nucleus," "allergic rhinitis," "chronic rhinosinusitis," and "neuromodulation."

The sneeze reflex is a complex protective mechanism divided into an initial sensory phase and an efferent respiratory phase, orchestrated by the ventromedial spinal trigeminal nucleus in the brainstem. Signal transmission strictly relies on small-diameter Trpv1 + nasal sensory neurons releasing Neuromedin B (NMB). Triggers range from chemical irritants to allergens. Pathological hyperactive sneezing is prominent in allergic rhinitis and Type 2 chronic rhinosinusitis (CRSwNP), driven by profound neuroimmune cross-talk. Conversely, Lateral Medullary Syndrome can abolish the ability to sneeze despite a preserved urge. Additionally, the photic sneeze reflex represents a visual-somatosensory cross-activation, while psychogenic intractable sneezing roots in psychological distress. For recalcitrant hyperactive sneezing, specific neuromodulation treatments, such as capsaicin desensitization and posterior nasal nerve (PNN) cryoablation or neurectomy, effectively disrupt the local neuro-secretory circuitry.

Sneezing transcends a simple automatic response, functioning as a highly coordinated neuroimmune reflex. Elucidating its precise neural circuitry provides critical insights for developing targeted pharmacological and procedural neuromodulation treatments for sneezing disorders, ultimately enhancing patient care.