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bioRxiv · 10.1101/242685

Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

Hegarty, D. M.·Hermes, S. M.·Morgan, M. M.·Aicher, S. A.
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Abstract

Corneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms.

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Hegarty, D. M., Hermes, S. M., Morgan, M. M., Aicher, S. A.. 2018-01-04. Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury. https://doi.org/10.1101/242685

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