TRPV1 + nociceptor neurons promote airway neurogenic inflammation in CVA via substance P-dependent macrophage M1 polarization

BACKGROUND: Cough variant asthma (CVA) is characterized by chronic cough and airway hypersensitivity, in which transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation plays a critical role. OBJECTIVE: substance P (SP)-dependent macrophage polarization. METHODS: , a dorsal root ganglion (DRG) neuron-RAW264.7 macrophage co-culture system, combined with TRPV1 knockdown and NK-1R blockade, was used to define the TRPV1-SP-macrophage polarization axis. RESULTS: neurokinin-1 receptor drove macrophages toward an M1 phenotype, upregulating pro-inflammatory markers. Inhibition of SP signaling blocked this polarization. CONCLUSIONS: Our results reveal a novel TRPV1-SP-macrophage M1 axis in CVA pathogenesis, suggesting that targeting this neuroimmune pathway may offer a therapeutic strategy for CVA.