Mechanisms of ocular surface pain

Abstract

Ocular pain is evoked upon activation of a small number of nociceptive neurons located at the trigeminal ganglion whose peripheral projections profusely innervate the cornea and conjunctiva. In healthy conditions, nerve impulse activity originated at peripheral nerve endings of these primary sensory neurons in response to noxious or potentially noxious stimuli acting on the ocular surface travels centrally and reaches second‐order neurons located at the trigeminal brain stem complex. In turn, these brainstem neurons send their axons to the contralateral posterior thalamic nuclei, where the third neurons along the ocular nociceptive pathway are found. Thalamic neurons send their axons to the primary somatosensory area of the brain cortex and, after brain cortex processing if this sensory inflow, nociceptive pain sensation is experienced.The activity of ocular nociceptor neurons is modified under inflammation. Inflammatory mediators released at the ocular surface increase the excitability of the nerve terminals. As a result, the impulse response of primary nociceptor neurons to noxious stimuli is increased, which constitutes the basis of hyperalgesia and leads to pain and other sensations such as gritty eyes, foreign body sensation, etc. experienced under ocular inflammation.After a lesion (including surgery) or disease that affects any nerve or neuron of the ocular somatosensory pathway, the activity and connectivity of the neurons involved in ocular pain is altered, sometimes permanently. The excitability of damaged neurons is long‐lasting increased, leading to ocular dysesthesia and development of neuropathic pain referred to the eye.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)