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.Le texte complet de cet article est disponible en PDF.
Key words : Capsaicin treatment, idiopathic rhinitis, nasal hyperreactivity, TRPV1, afferent nerves, TRPV1-SP signaling pathway
Abbreviations used : CDA, CGRP, FITC, HC, IR, NANIR, NEC, NHR, NKA, PGP 9.5, PI, PNIF, SP, SPT, TRE, TRPA1, TRPM8, TRPV1, TUNEL, VAS
| L.V.G. is supported by a grant of the Agency for Innovation by Science and Technology in Flanders, Belgium (IWT). P.W.H. is a recipient of a senior researcher fellowship from the Fund for Scientific Research Flanders, Belgium (FWO). M.M.W. is a postdoctoral researcher of the Fund for Scientific Research (FWO), Flanders, Belgium. G.B. is supported by a governmental grant (Odysseus program, G.0905.07, FWO). This work was also supported by grants from the Belgian Federal Government (IUAP P6/28), the FWO (G.0565.07 and G.0686.09), IWT (TBM project 130260), and the Research Council of the KU Leuven (GOA 2009/07 and 14/011, EF/95/010 and PFV/10/006).
| Disclosure of potential conflict of interest: L. Van Gerven has been supported by one or more grants from IWT. P. W. Hellings is a Board member for the European Academy of Allergy and Clinical Immunology, the European Respiratory Society, and EAFPS; has received one or more grants from or has one or more grants pending with GlaxoSmithKline and Stallergenes; and has received one or more payments for lecturing from or is on the speakers' bureau for GlaxoSmithKline, MSD, and Stallergenes. The rest of the authors declare that they have no relevant conflicts of interest.