The anatomical and electrophysiological basis of peripheral nasal trigeminal chemoreception

The trigeminal nerve (TN) provides sensory information from the eyes, nose, and mouth. A subset of trigeminal nerve fibers, particularly those containing the neuropeptides substance P and calcitonin gene-related peptide (CGRP), responds to chemical irritants in the environment. Axons in the ethmoid and nasopalatine branches of the trigeminal nerve innervate the nasal mucosa where they ramify repeatedly. TN endings extend close to the nasal epithelial surface stopping at the line of tight junctions only a few micrometers from the surface. A single ethmoid nerve axon may send branches to the nasal mucosa, olfactory bulb, and the spinal trigeminal complex. Traditionally, irritants are thought to stimulate free TN endings in the nasal epithelium. Recently, however, solitary chemoreceptor cells (SCCs) have been found scattered throughout the nasal cavity. The SCCs are contacted by TN fibers and may express T2R ''bitter-taste'' receptors alpha-gustducin, and TRPM5. Peripheral trigeminal electrophysiological recordings in response to irritants have been obtained from the mucosa (negative mucosal potential, NMP) and the nerve to analyze characteristics of trigeminal stimuli. Responses to a wide variety of irritants have been recorded from the ethmoid nerve. In general, the more lipid soluble the compound, the lower the threshold. Nerve recordings have also suggested several mechanisms by which irritants elicit responses. Bitter substances elicit responses from the ethmoid nerve and cause a change in respiration indicating stimulation via SCCs. SCCs themselves respond to chemical stimuli and may be contributing to the detection of nasal irritants.