Increased nerve fiber expression of sensory sodium channels Nav1.7, Nav1.8, And Nav1.9 in rhinitis.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Keh
Siew M
SM
Peripheral Neuropathy Unit, Hammersmith Hospital, Faculty of Medicine, Imperial College London, London, UK.
Facer
Paul
P
Simpson
Karen D
KD
Sandhu
Guri
G
Saleh
Hesham A
HA
Anand
Praveen
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009297:Nasal Mucosa / Q000473:pathology; D009412:Nerve Fibers / Q000473:pathology*; D020932:Nerve Growth Factor / Q000032:analysis; D009475:Neurons, Afferent / Q000473:pathology*; D009479:Neuropeptides / Q000032:analysis*; D012220:Rhinitis / Q000473:pathology*; D012221:Rhinitis, Allergic, Perennial / Q000473:pathology; D006255:Rhinitis, Allergic, Seasonal / Q000473:pathology; D015222:Sodium Channels / Q000032:analysis*; D013601:T-Lymphocytes / Q000473:pathology; D014420:Turbinates / Q000473:pathology; D043222:Ubiquitin Thiolesterase / Q000032:analysis
D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568317:SCN10A protein, human; C491886:SCN11A protein, human; C486866:SCN9A protein, human; D015222:Sodium Channels; C482860:UCHL1 protein, human; D020932:Nerve Growth Factor; D043222:Ubiquitin Thiolesterase