Mechanisms of Pain and Photophobia in Migraine and Dry Eye

Project Summary
Ocular pain and photophobia are common and debilitating conditions associated with migraine and dry eye
disease (DED). Persistent pain, dry eye, and/or photophobia are also experienced by nearly 40% of patients
who have received refractive surgery. A common neuroanatomical substrate in migraine, DED, and refractive
surgery is the trigeminal nerve, specifically the ophthalmic branch, which is involved in reflex homeostatic
regulation of the cornea and dura. It is well known that damage to these reflex circuits leads to overt
sensations of pain, yet the underlying mechanisms are poorly understood and effective non-opioid treatments
are lacking. We hypothesize that the trigeminal neurons projecting to the cornea and dura are modulated by
feedback from light-sensing cells in the eye, as well as by interaction with infiltrating immune cells leading to
dysregulation of the reflex pathways and amplification of sensory responses – causing hypersensitivities to
touch and light (photophobia). We will test this hypothesis in rodent models of migraine, DED, and refractive
surgery by identifying molecular mechanisms and neural pathways common to the three pain models, using
neuroanatomical, physiological, and behavioral approaches. Experiments will include investigation of potential
therapeutic targets, including CGRP, TRPM3, and melanopsin, all of which have been previously implicated in
photophobia. These studies will elucidate key cellular and molecular changes underlying the development of
ocular pain and photophobia in migraine, DED, and refractive surgery, and will guide therapeutic development.

Grant Number: 5U01EY034680-04
NIH Institute/Center: NIH
Principal Investigator: SUE AICHER