Nasal Trigeminal Chemoreceptors May Have Affector and Effector Functions

Abstract

The nasal cavity embraces a wide variety of chemoreceptors, including those of the olfactory, vomeronasal, and trigeminal systems. Chemical stimulation of nasal trigeminal receptors is usually associated with pain or irritation. Accordingly, trigeminal fibers sensitive to chemical irritants have been considered part of the common chemical sense [1], although, more recently, this trigeminal “chemosense” has been called chemesthesis [2,3]. The nasal cavity is innervated by the ethmoid and nasopalatine branches of the trigeminal nerve. Ethmoid nerve endings in the nasal cavity respond to a wide variety of chemical stimuli [3]. Ethmoid nerve fibers which respond to chemical stimuli appear to be capsaicin-sensitive, containing calcitonin gene-related peptide (CGRP) and substance P [4]. For the present report, experiments were performed on rats injected with capsaicin (50 mg/kg) on the 2nd day postnatally and examined at least 40 days later. Systemic capsaicin treatment in neonatal animals produces a long-lasting insensitivity to noxious chemicals (for review, see [5]). In our experiments, neonatal capsaicin administration eliminated ethmoid nerve responses to chemical stimuli, while leaving responses to mechanical stimuli intact. In addition, neonatal capsaicin administration decreased the number of CGRP-containing fibers in the ethmoid nerve by 90% or more. These were primarily unmyelinated, or fine myelinated fibers. Such immunoreactive fibers reach to within 1 p.m of the surface of the nasal epithelium [6]. Capsaicin-sensitive, CGRP-immunoreactive fibers course alongside olfactory receptor axons within the olfactory nerve to terminate within glomeruli of the olfactory bulb. Removal of the trigeminal ganglion eliminated such CGRPimmunoreactive fibers from the olfactory nerve and bulb. Double-label experiments, in which different fluorescent retrograde tracers were injected into the olfactory bulb and nasal epithelium, revealed that single trigeminal ganglion cells have a sensory arborization with branches in both the nasal epithelium and olfactory bulb. We suggest that trigeminal nerve fibers in the nasal cavity have both an affector and effector function. Capsaicin-sensitive, peptidergic sensory neurons in other systems are known to release, via an axon reflex, neuropeptide mediators which have an effector function on surrounding tissues [7]. Accordingly, nasal trigeminal sensory fibers may not only transmit sensory information centripetally, but may act via an axon reflex to release neuroactive peptides into the nasal mucosa and olfactory bulbar neuropil, thereby affecting processing of simultaneous or subsequent olfactory stimuli. Thus, trigeminal chemoreception should not be viewed as a simple sensory system that can be studied in isolation, but as a potential modulator of olfactory processes.