New concepts of neural regulation in human nasal mucosa

Abstract

Nasal mucosa is innervated by multiple subsets of nociceptive, parasympathetic and sympathetic nerves. These play carefully coordinated roles in regulating glandular, vascular and other processes. These functions are vital for cleaning and humidifying ambient air before it is inhaled into the lungs. The recent recognition of distinct classes of nociceptive nerves with unique patterns of sensory receptors that include seven transmembrane G-protein coupled receptors, new families of transient receptor potential and voltage and calcium gated ion channels, and combinations of neurotransmitters that can be modulated during inflammation by neurotrophic factors has revolutionized our understanding of the complexity and subtlety of nasal innervation. These findings may provide a rational basis for responses to air temperature changes, culinary and botanical odorants ("aromatherapy"), and inhaled irritants in conditions as diverse as idiopathic nonallergic rhinitis, occupational rhinitis, hyposmia, and multiple chemical sensitivity.

Fig. 1

Axon response. Hypertonic saline (HTS) stimulates as yet unknown mechanisms in the nasal mucosa that lead to nociceptive nerve depolarization. This leads to central nervous system perceptions of pain, blockage or drip, and the local mucosal release of substance P (SP), neurokinin A (NKA) and potentially other neurotransmitters. Receptors for these tachykinins are localized to glands. This suggests that tachykinins released by the axon response mechanism near submucosal glands stimulate exocytosis of serous and mucous cell products. No changes in vascular permeability or vasodilation were detected indicating the absence of a vascular component to human airway axon responses.

Fig. 2

Schematic nerve depolarization curve. Resting membrane potential is maintained at about −40 mV by potassium channels (K_ir, K_2P). Sensory and regulatory channels initiate depolarization. Voltage gated sodium channels (Na_v) and calcium channels (Ca_v) induce full depolarization to 0 mV. The cell is repolarized by voltage and calcium activated potassium channels (K_v and K_Ca). The numbers of recognized members for each type of channel are in brackets. Used with permission of the copyright holder.

Fig. 3

Schematic TRPV1 protein with 6 transmembrane regions and the intramembrane loop that forms the cation pore. Various ligands are shown. Bradykinin binds to its B2 receptor and activates 12- and 15-lipoxygenase (12-LO, 125-LO) and phospholipase C (PLC) and protein kinase A (PKA) that phosphorylates the carboxy-terminus of the protein. Used with permission of the copyright holder.

Fig. 4

TRP thermometer and aromatherapy in the trigeminal chemosensory nervous system. Used with permission of the copyright holder.