Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 5; pp. 1332 - 1339.e3
• Main Authors: Van Gerven, Laura, Alpizar, Yeranddy A., Wouters, Mira M., Hox, Valérie, Hauben, Esther, Jorissen, Mark, Boeckxstaens, Guy, Talavera, Karel, Hellings, Peter W.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2014; Elsevier; Elsevier Limited
• Subjects: Adult; afferent nerves; Allergies; Allergy and Immunology; Biological and medical sciences; Capsaicin - administration & dosage; Capsaicin - adverse effects; Capsaicin treatment; Cells, Cultured; Cocaine; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; Humans; idiopathic rhinitis; Immunopathology; Male; Mast Cells - metabolism; Mast Cells - pathology; Medical sciences; Middle Aged; nasal hyperreactivity; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Nasal Sprays; Neuropeptides; Non tumoral diseases; Nose; Otolaryngology; Otorhinolaryngology. Stomatology; Proto-Oncogene Proteins c-kit - biosynthesis; Rhinitis, Allergic, Perennial - drug therapy; Rhinitis, Allergic, Perennial - metabolism; Rhinitis, Allergic, Perennial - pathology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensory System Agents - administration & dosage; Sensory System Agents - adverse effects; TRPV Cation Channels - biosynthesis; TRPV1; TRPV1-SP signaling pathway; Ubiquitin Thiolesterase - biosynthesis; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; CDA; afferent nerves; TRE; idiopathic rhinitis; PGP 9.5; VAS; NANIR; Capsaicin treatment; FITC; TUNEL; SPT; NHR; TRPM8; SP; nasal hyperreactivity; TRPA1; NKA; TRPV1-SP signaling pathway; IR; TRPV1; NEC; PI; HC; CGRP; PNIF; Fluorescein isothiocyanate; Calcitonin gene–related peptide; Transient receptor potential cation channel subfamily M, receptor 8; Propidium iodide; Terminal deoxynucleotide transferase dUTP nick end labeling; Cold dry air; Visual analog scale; Therapeutic response evaluation; Transient receptor potential cation channel subfamily V, receptor 1; Neurokinin A; Protein gene product 9.5; Healthy control subject; Substance P; Skin prick test; Nonallergic noninfectious rhinitis; Peak nasal inspiratory flow; Nasal epithelial cell; Transient receptor potential cation channel subfamily A, receptor 1; Human; Immunopathology; Nose disease; Hyperreactivity; Rhinitis; Capsaicin; Idiopathic; Gene overexpression; Ionic channel; Transitory; Nerve; Immunology; Treatment; Signaling pathway; Nose; ENT disease; Cations; TRPVI-SP signaling pathway; Biological receptor
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.08.026

Idiopathic rhinitis (IR) is a prevalent condition for which capsaicin nasal spray is the most effective treatment. However, the mechanisms underlying IR and the therapeutic action of capsaicin remain unknown. We sought to investigate the molecular and cellular bases of IR and the therapeutic action of capsaicin. Fourteen patients with IR and 12 healthy control subjects (HCs) were treated with intranasal capsaicin. The therapeutic effect was assessed in patients with IR by using visual analog scale and therapeutic response evaluation scores, and nasal hyperreactivity was evaluated by means of cold dry air provocation. Nasal samples served to measure the levels of neuromediators and expression of chemosensory cation channels, protein gene product 9.5 (PGP 9.5), and the mast cell marker c-kit. The effects of capsaicin were also tested in vitro on human nasal epithelial cells and mast cells. Patients with IR had higher baseline transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) expression in the nasal mucosa and higher concentrations of substance P (SP) in nasal secretions than HCs. Symptomatic relief was observed in 11 of 14 patients with IR after capsaicin treatment. Expression of TRPV1; transient receptor potential cation channel subfamily M, receptor 8 (TRPM8); and PGP 9.5 was only reduced in patients with IR after capsaicin treatment. Capsaicin did not alter c-KIT expression or nasal epithelial morphology in patients with IR and HCs nor did it induce apoptosis or necrosis in cultured human nasal epithelial cells and mast cells. IR features an overexpression of TRPV1 in the nasal mucosa and increased SP levels in nasal secretions. Capsaicin exerts its therapeutic action by ablating the TRPV1-SP nociceptive signaling pathway in the nasal mucosa.