title: TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors.
abstract: We addressed the hypothesis that allergic inflammation in guinea pig airways leads to a phenotypic switch in vagal tracheal cough-causing, low-threshold mechanosensitive Aδ neurons, such that they begin expressing functional transient receptor potential vanilloid (TRPV1) channels. Guinea pigs were actively sensitized to ovalbumin (OVA) and beginning 21 days later exposed via aerosol to OVA daily for 3 days. Tracheal-specific neurons were identified in the nodose ganglion using retrograde tracing techniques. Tracheal specific neurons were isolated, and mRNA expression was evaluated at the single-neuron level using RT-PCR analysis. Electrophysiological studies have revealed that the vast majority of vagal nodose afferent nerves innervating the trachea are capsaicin-insensitive Aδ-fibers. Consistent with this, we found <20% of these neurons express TRPV1 mRNA or respond to capsaicin in a calcium assay. Allergen exposure induced de novo TRPV1 mRNA in a majority of the tracheal-specific nodose neurons (P < 0.05). The allergen-induced TRPV1 induction was mimicked by applying either brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) to the tracheal lumen. The BDNF-induced phenotypic change observed at the level of mRNA expression was mimicked using a calcium assay to assess functional TRPV1 ion channels. Finally, OVA exposure induced BDNF and GDNF production in the tracheal epithelium, the immediate vicinity of the nodose Aδ -fibers terminations. The induction of TRPV1 in nodose tracheal Aδ -fibers would substantively expand the nature of stimuli capable of activating these cough-causing nerves.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
authors.forename: Tina Marie
authors.initials: TM
authors.lastname: Lieu
authors.forename: Allen C
authors.initials: AC
authors.lastname: Myers
authors.forename: Sonya
authors.initials: S
authors.lastname: Meeker
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D020013:Calcium Signaling; D002478:Cells, Cultured; D015870:Gene Expression; D020869:Gene Expression Profiling; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology; D006168:Guinea Pigs; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009620:Nodose Ganglion / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059010:Single-Cell Analysis; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000276:immunology / Q000294:innervation* / Q000473:pathology
chemical_list: D000485:Allergens; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D010047:Ovalbumin; D020932:Nerve Growth Factor