Trigeminal Function in Sino-Nasal Health and Disease

Abstract

The upper airway (nasal passages, paranasal sinuses, pharynx, and glottis) provides the sentinel portion of the human respiratory tract, with the combined senses of olfaction (cranial nerve I) and trigeminal sensation (cranial nerve V) signaling the quality of inspired air. Trigeminal function also complements the sense of taste (in turn mediated by cranial nerves VII, IX and X), and participates in the genesis of taste aversions. The ability of trigeminal stimulation in the upper aero-digestive tract to trigger a variety of respiratory and behavioral reflexes has long been recognized. In this context, the last three decades has seen a proliferation of observations at a molecular level regarding the mechanisms of olfaction, irritation, and gustation. Concurrently, an ever-widening network of physiological interactions between olfaction, taste, and trigeminal function has been uncovered. The objective of this review is to summarize the relatively recent expansion of research in this sub-field of sensory science, and to explore the clinical and therapeutic implications thereof.

Keywords: airflow; cough; glossopharyngeal nerve; headache; irritation; larynx; meninges; nose; paranasal sinuses; receptors; reflexes; rhinitis; sinusitis; stimulation; trigeminal nerve.

Figure 1

Surface innervation by the fifth (trigeminal) cranial nerve. From reference [1].

Figure 2

Subsurface distribution of the trigeminal nerve (CrN V) in humans. Branches: Ophthalmic (V1 red), maxillary (V2 green), and mandibular (V3 blue). From reference [1].

Figure 3

Nerve fiber sub-populations, arranged from largest diameter and myelinated (fastest) to smallest diameter/unmyelinated (slowest). From reference [20].

Figure 4

Mucosal “free” nerve endings (terminating below “tight junctions”) and solitary chemosensory cells (in contact with the mucosal lumen). With permission from reference [21].

Figure 5

Two major classes of membrane receptors: (A) ion channels and (B) GPCRs. Most nociceptors (e.g., TRPV1, TRPM8, TRPA1, ASIC, nAChR, and P2X) are ion channels. With permission from reference [25].

Figure 6

Thermal response spectra of common human TRP (‘thermoTRP’) channels. Adapted from reference [31].

Figure 7

Procedure for obtaining human trigeminal irritation thresholds by lateralization. Active stimulus and “control” were presented with laterality randomized. Both active stimulus and diluent are colorless and transparent, thereby avoiding cueing. Source: Author.

Figure 8

Innervation of (and reflex effects within) the trigeminal nerve distribution. n. Arrows indicated the direction of nerve impulse conduction (green) and biochemical diffusion (red). With permission from reference [21].

Figure 9

Parallel excitation of trigeminal nerve fibers by free nerve endings (invested with TRP nociceptors) and solitary chemosensory cells or “SCCs” (invested with bitter taste receptors). SCCs make direct contact with the airway lumen and respond to bitter substances that cannot diffuse beyond tight junctions to reach free nerve endings. With permission from reference [120].