Corneo‐conjunctival sensory neuron: Types, transduction channels and codification of nerve impulses

Abstract

The cornea and the conjunctiva are innervated by the peripheral projections of a small number of primary sensory neurons whose somata are located at the ophthalmic region of the trigeminal ganglion. Most trigeminal neurons innervating the ocular surface are small and medium size, and contain neuropeptides such as SP and CGRP. Functionally, ocular surface neurons have been classified into five main neuronal types, based on their response to multiple modalities of stimuli (mechanical forces, heat, cold, H+, chemical substances, etc.). Polymodal nociceptors (activated by several modalities of stimulus, mechanical energy, heat, H+, and chemical irritants), mechanonociceptors (activated by mechanical energy), cold thermoreceptors (activated by temperature reductions and hyperosmolarity) are found in the cornea, the sclera and the conjunctiva. Besides, low‐threshold mechanoreceptors (activated by mechanical forces of low intensity) are found in the corneoscleral limbus and the lid border, and pruriceptors (activated by pruritogen substances) have been described in the tarsal conjunctiva, close to the lid margin.The ability to respond to the different modalities of stimulus lies in the types of transducing channels that each type of neuron expresses at its peripheral nerve endings. Sensory transduction involves the conversion of the physical or chemical stimuli acting on the nerve terminal into electrical energy, that is, into a local change of membrane potential that, if it is large enough, will generate action potentials that will travel along the axon to be processed by the CNS. So that, nerve terminals with TRPV1 channels are directly gated by heat, H+, and several chemical irritants such as capsaicin; nerve terminals with Piezo2 channels will be activated by mechanical forces; TRPM8 channels provide nerve terminals sensitivity to cold and osmolarity increases; et cetera.Ocular sensory neurons also express other ion channels that contribute to coding, that is to help the sensory neuron to establish a correspondence between the characteristics of the stimulus (intensity, temporal course, etc.) and specific parameters of the firing it induces. Voltage‐gated Ca2+, Na+ and K+ channels as well as cyclic nucleotide‐gated channels, among others, contribute to define the firing frequency and pattern to encode the traits of the stimulus. Thus, the ion channels present in the nerve terminals of each class of ocular sensory neuron provide the neurons the ability to detect and encode one or several modalities of stimulus, which constitutes the origin of the different sensations evoked on the ocular surface.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)