International Rhinologic Society Rhinology 0300-0729 2026 07 07 Pharmacological silencing of nasal TRPV1+ nociceptors ameliorates eosinophilic infiltration but exacerbates neutrophilic infiltration in murine models of allergic rhinitis EN F. YeDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China Y. Tao Department of Otolaryngology-Head and Neck Surgery, Shenzhen Third People's Hospital, Shenzhen, China J. ChenDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China R. WangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China Y. LiDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China Z. ShiDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Naso-Orbital-Maxilla and Skull Base Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China Q. YangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Naso-Orbital-Maxilla and Skull Base Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, China Journal Article 3484 10.4193/Rhin25.667 BACKGROUND: The pathogenesis of allergic rhinitis (AR) involves hyperreactivity of both the immune and neural systems. While sensory nerves detect allergens and release neuropeptides that directly participate in immune regulation, their precise role within the AR inflammatory network remains incompletely elucidated. METHODOLOGY: Using house dust mite (HDM) and ovalbumin (OVA)-induced murine AR models, we selectively silenced nasal TRPV1-expressing sensory nerves pharmacologically with QX-314 (co-administered with capsaicin) and Resiniferatoxin (RTX). The effects of neuronal silencing on animal behavior, allergen-specific IgE levels, inflammatory cell nfiltration, and immune cell populations were systematically evaluated via immunofluorescence, histological staining, ELISA, and flow cytometry. RESULTS: Both QX-314 and RTX effectively silenced TRPV1+ sensory neurons in the trigeminal ganglia and significantly downregulated the expression of neuropeptides CGRP and SP. Silencing nasal TRPV1+ sensory nerves markedly reduced eosinophilic infiltration and levels of the associated marker ECP in the nasal mucosa of AR model mice. Unexpectedly, it also led to a significant increase in neutrophilic infiltration and MPO-positive cells. RTX-mediated ablation further compromised epithelial barrier integrity and aggravated the local inflammatory burden. Flow cytometric analysis further confirmed that RTX-mediated ablation of TRPV1+ neurons significantly decreased the proportions of infiltrating eosinophils and B cells, but increased the proportion of neutrophils in the OVA model. CONCLUSIONS: Silencing nasal TRPV1+ sensory nerves exerts a dual immunomodulatory effect in AR, attenuating eosinophilic inflammation while promoting neutrophilic infiltration. This reveals a critical neuro-immune balance in the nasal mucosa and suggests that precisely targeted neuromodulation strategies are required to suppress allergic inflammation.