Increased Nerve Fiber Expression of Sensory Sodium Channels Nav1.7, Nav1.8, and Nav1.9 in Rhinitis

Authors


  • Authors' contributions: s.m.k. collected the biopsies and prepared the manuscript, p.f. performed the immunocytochemical studies, k.d.s. helped with the study design and analysis of the data; g.s. and h.a.s. initiated and supervised the clinical aspects of the study and the manuscript, pa initiated and supervised the tissue aspects of the study and helped with interpretation of the data.

  • Competing interests: K.D.S. is an employee of GlaxoSmithKline and participates in an employee share scheme.

Abstract

Introduction: Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis.

Materials and Methods: Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed.

Results: All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P = .0004; Nav1.8, P = .028; Nav1.9, P = .02) and nonallergic (Nav1.7, P = .006; Nav1.8, P = .019; Nav1.9, P = .0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P = .01) and epithelial NGF immunoreactivity (P = .03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P = .06; macrophages, P = .044; T cells, P = .007) but not nonallergic rhinitis.

Conclusion: The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis.

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