Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms w ere evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 mu l) 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 con centrations of specific mucus constituents. Nasal cavity air-space volume w as assessed by acoustic rhinometry (AcRh). The distribution of substance-P- preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ revers e transcriptase-polymerase chain reaction. Unilateral HTS induced unilatera l dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protei n, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, r eflex-mediated effects were minor. There were no changes in IgG or AcRh mea surements. NK-1 receptor mRNA was localized to submucosal glands. HTS cause d pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through acti ons on submucosal gland NK-1 receptors. Vascular processes, including plasm a exudation, filling of venous sinusoids, and mucosal edema were not induce d in these normal subjects.