Corneal sensory nerve function: An overview

Abstract

Somatosensory innervation of the cornea is provided by the peripheral axons of a small number of primary sensory neurons located in the ophthalmic region of the trigeminal ganglion. Corneal sensory nerve fibres are heterogeneous and may express different neurotransmitters and ion channels involved in transduction and coding of the stimuli acting on the tissue. Based on their activation by one or several types of physical and chemical stimuli, corneal nerve fibres are classified as polymodal nociceptors, mechanonociceptors and cold thermoreceptors. Impulse activity originated at corneal sensory nerves reaches second‐order neurons located at the lower brainstem, from where sensory information travels to the contralateral posterior thalamus and, then, to the brain cortex.After processing, the activation of the different classes of corneal neurons results in different sensations that depend on the type of primary sensory neuron initially activated by the stimulus, although pain is the main sensation elicited by corneal stimulation. Sensations originated at the cornea are explored by esthesiometry, allowing to quantify the threshold, intensity and quality of the evoked sensations. Sensitivity of the ocular surface is reduced with age and altered by several pathological processes that affect sensory innervation, either ocular (such as allergic keratoconjunctivitis, infectious keratitis, eye surgery, hereditary corneal dystrophies, dry eye, etc.) or systemic diseases, such as diabetes and peripheral neuropathies.A prominent feature of ocular nociceptors is their sensitization by the inflammatory mediators released after noxious stimulation or tissue injury, while cold thermoreceptor activity is inhibited by inflammatory substances. Both the spontaneous and the stimulus‐evoked activity increases in sensitized nociceptors, which causes sustained pain and hyperalgesia. After corneal sensory nerves damage (produced as a consequence of an ocular or systemic disease, or by accidental or surgical injury), part of sensory nerves degenerates leading to reduced sensitivity to natural stimulation in the affected area. At the same time, axons start to regenerate and to recover the ability to transduce and encode the stimulus. During this regeneration process, cold thermoreceptor and nociceptor nerves may become hyperexcitable due to changes in their expression/activity of ion channels, which give rise to dryness sensation and ocular neuropathic pain.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)