Establish the mouse sneeze model. (A) Representative traces showing the simultaneous Whole Body Plethysmography (WBP) and audio recordings of a freely-moving WT mouse upon exposure to aerosolized capsaicin solution (12 μM). The WBP and audio peaks (indicated by the arrows) correlate well and indicate sneezing-like responses. (B) Transection of the anterior ethmoid nerve (AEN), which provides sensory innervation to the nose, significantly reduced sneezing-like responses to aerosolized capsaicin (12 μM) and histamine (100 mM) solution. (C) Electromyography (EMG) recording showing the representative muscle contractions of diaphragm and external oblique abdominus of mice in eupnea and during sneezing responses to nasal challenge of capsaicin (12 μM). Muscular contractions that significantly increase over regular respiratory movement and interrupt the respiratory rhythm were counted as sneezing-related responses (indicated by red arrows). (D) Nasal instillation of resiniferatoxin (RTX, 50 ng in 2 μl/ nostril) ablated nasal Trpv1+ sensory fibers and eliminated sneezing-related muscular responses to capsaicin, as revealed by EMG recording. (E) Nasal secretion was significantly increased after capsaicin-induced sneezes, compared with baseline (BL) or saline control. Each dot represents an individual mouse (n=4–11 mice/group). Data are represented as mean ± SEM. **P≤0.01, ***P≤0.001, n.s. not significant. See also Figure S1, Videos S1 and S2, and Table S1.