title: Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans.
abstract: Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 microliters) and higher concentrations (3 x NS, 6 x NS, 12 x NS, 24 x NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA. baraniuj@gunet.georgetown.edu
authors.forename: J N
authors.initials: JN
authors.lastname: Baraniuk
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: A
authors.initials: A
authors.lastname: Yuta
authors.forename: S Y
authors.initials: SY
authors.lastname: Fang
authors.forename: K
authors.initials: K
authors.lastname: Naranch
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012462:Saline Solution, Hypertonic; D013373:Substance P / Q000378:metabolism*
chemical_list: D018040:Receptors, Neurokinin-1; D012462:Saline Solution, Hypertonic; D013373:Substance P