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Chris Schaumburg, Katherine Held, Euikyun Oh, Sveti Ugarte, Larry Wheeler, Margarita Calonge, Jerry Niederkorn, Stephen Pflugfelder, Robert Fox, Michael Stern; Mice with Desiccating Stress-Induced Dry Eye Develop Trigeminal Neuralgia, Despite Decreased Corneal Sensitivity and Nerve Fiber Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2194.
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Pain is a major symptom of patients suffering from chronic Dry Eye disease. To begin to understand if the immunopathogenesis of desiccating stress (DS)-induced Dry Eye is associated with a pain response, corneal sensitivity, corneal nerve fiber density, neuropeptides and trigeminal neuralgia were evaluated over the course of disease.
Dry Eye disease was induced by exposing female C57BL/6 mice to desiccating stress (DS: subcutaneous scopolamine (1.0mg/0.2ml) TID; humidity <40%; sustained airflow). At various time points mice were evaluated for corneal sensitivity using von Frey filaments (Dixon up-down method), corneal nerve fibers with immunohistochemistry, neuropeptides using ELISA and trigeminal neuralgia with behavorial testing.
IHC on flat mount whole corneas revealed a significant decrease (p<0.01) corneal nerve fiber density at Day 10, 15 and 20 of DS using neuronal class III beta-tubulin (Tuj1+) staining. Mice with Dry Eye disease also developed decreased corneal sensitivity very early, at Day 1 (0.21±0.10 gram force) and Day 3 (0.41±0.14 gram force; p=0.05) of DS compared to baseline (0.04±0.006 gram force). Mice with Dry Eye disease also developed robust trigeminal neuralgia by Day 15 (pain behavorial score = 4.67±.39 out of a maximum of 6.0; p<0.001), which was associated with upregulation of neuropeptides in the trigeminal ganglia; calcitonin gene related peptide (CGRP) and substance P were significantly (p=0.05) upregulated in the trigeminal ganglia by Day 15 of DS.
These data suggest that DS mice develop trigeminal neuralgia, despite decreased corneal sensitivity and nerve fiber degeneration during the progression of experimental Dry Eye disease.
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