Conscious sensations and protective reflexes driven by eye surface nerves in health and disease

The trigeminal primary sensory neurons that innervate the ocular surface, especially the cornea, have been classified in three functional types: polymodal nociceptors, mechano‐nociceptors and cold thermoreceptors. These sensory nerves are responsible for the conscious sensations evoked in response to ocular surface stimulation as well as for the regulation of tearing and blinking, and they are also involved in the trophic maintenance of the ocular tissues. Depending on the transducing channels they express in their membrane, sensory nerves from the ocular surface respond to different types of stimulus and, after this information is processed by the CNS, different conscious sensations are evoked: corneal mechano‐nociceptors' activation led to pricking pain; polymodal nociceptors evoke burning irritation, and cold thermoreceptors' activation may evoke freshness/cold/dryness/pain depending on the subtype of cold thermoreceptor neuron activated by the stimulus. While reflex blinking and tearing are driven by the activation of polymodal nociceptors as the afferent arm of the reflex, basal blinking and tearing rate are under the control of cold thermoreceptors' activity. During inflammation and after injury (such as UV‐induced keratitis, allergic keratoconjunctivitis, corneal surgery, tear‐deficient dry eye) the activity of corneal sensory nerves is modified in both eyes, even when inflammation or damage affects only one eye. The abnormal corneal sensory nerve activity constitutes the basis for the discomfort, dryness and pain sensations experienced under these conditions. Also, protective mechanisms depending on ocular nerve activity such as blinking and tearing become altered. (Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/ 10.13039/50110001103 , and CIPROM/2021/48 from the Generalitat Valenciana, Spain)