102) Corneal hyperalgesia after abrasion injury

Corneal nerve injury resulting from systemic diseases or damage to the ocular surface can cause either hyperalgesia or hypoalgesia. We tested the hypothesis that neuropathic changes in corneal nerve fibers underlie changes in ocular sensation using a corneal abrasion injury in rats. A unilateral central corneal injury was made using topical application of heptanol in Sprague-Dawley rats. At time points after corneal abrasion injury, stereotypic nociceptive eye wipe responses to ocular application of noxious menthol were measured in either the abraded eye or the non-abraded control eye. At the conclusion of behavioral testing, rats were euthanized and perfused with aldehydes. The corneas were removed and processed for immunohistochemistry for beta-tubulin and nociceptive molecular markers. Corneal fibers were visualized with confocal microscopy and analyzed using Imaris software. Rats tested on their injured eye 24 hours after abrasion showed significantly more eye wipe responses to ocular application of menthol than rats tested on their uninjured eye. Paradoxically, abraded corneas from the 24 hour time point had dramatically reduced corneal fiber density. One week post-injury, rats tested on the injured eye had similar numbers of eye wipes to noxious menthol stimulation as control rats. While corneal fiber density showed evidence of recovery at one week, it was reduced compared to uninjured corneas. Abrasion injury reduces corneal fiber density; however, this reduction does not appear to be correlated with behavioral responses to noxious corneal stimulation. Our results suggest that the neurochemical content or pathological changes in corneal fibers will be a better predictor of pain sensitivity at the corneal surface than overall nerve fiber density. Recent studies have also shown that chemical stimulation with TRP channel agonists can alter corneal nerve morphology as well. Further studies are needed to fully understand the neuropathic changes that occur in corneal nerve fibers after injury.