Abstract
Purpose :
Hypersensitivity and hyperalgesia are problematic symptoms of chronic pain induced by dry eye. Ocular neuropathic pain was previously reported to involve activation of neurons and glial cells at the level of the trigeminal nucleus. However, the pathomechanism in the trigeminal ganglion is unknown. We hypothesize that dry eye induces hypersensitivity and hyperalgesia through activation of neurons and satellite glial cells in the trigeminal ganglion.
Methods :
We created and tested VDT user dry eye model using Sprague-Dawley rats.
The right eye was compared as the dry eye and the left eye as the control eye with ocular protection (N=6). We performed phenotypic analysis of tear volume, corneal epithelial damage score, hypersensitivity (blink frequency), and hyperalgesia (hypertonic saline eye drop stress test). We analyzed the localization of neurons and satellite glial cells in the trigeminal ganglion by immunohistochemistry. In addition, gene expression related to neuropathic pain was analyzed by qRT-PCR. Two-tailed Student's t-test was used for statistical analysis.
Results :
In dry eyes, decreased tear fluid, corneal epithelial damage, hypersensitivity and hyperalgesia were observed. Satellite glial cells were present enveloping the neurons in the trigeminal ganglion. There was increased mRNA expression indicating neural hyperactivity (Fos: 3.313±0.447, p=0.0018) and satellite glial cell activation (Kcnn3: 2.449±0.479, p=0.0069). Interestingly, mRNA expression of neuropeptides such as CGRP (calcitonin gene-related peptide Calca: 3.733±1.320, p=0.0475) and inflammatory cytokines such as IL-1β (Il1b: 5.324±0.969, p=0.0053) were also increased.
Conclusions :
Our results support the hypothesis that dry eye induces hypersensitivity and hyperalgesia through activation of neurons and satellite glial cells in the trigeminal ganglion. In addition, gene expression levels of neuropeptides that activate peripheral cells and inflammatory cytokines that activate neurons were increased, suggesting the possibility of neuropathic pain development in the trigeminal ganglion due to neuron-glia Interactions. Further analysis of the protein-level localization and expression of neuropeptides and inflammatory cytokines will be needed to understand the pathomechanism.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.