Figure 7.

Graphic summary of the main findings. Corneal cold-sensitive nerves with the cold sensor, transient receptor potential melastatin 8 (TRPM8), are classified into high background activity-low threshold (HB-LT) cold thermoreceptor, and low-background activity-high threshold (LB-HT) cold thermoreceptor. The polymodal nociceptor, TRPV1, is expressed in corneal cold-sensitive nerves characterized by LB-HT cold thermoreceptors that provide dryness sensation, as well as in a part of the corneal cold-insensitive nerves that provide pain. Tear deficiency induced by lacrimal gland excision sensitizes the TRPV1-mediated excitation in corneal nerves, possibly mediated by the increase in activated satellite glial cells around the corneal neurons in the trigeminal ganglion. The changes in the sensitivities of corneal nerves might relate to the induction of dryness and discomfort sensation and pain under chronic tear deficiency.