Upregulation of the mu‐opioid receptor in the cornea and trigeminal ganglion following corneal inflammatory pain

Abstract

AbstractOcular pain following corneal injury is frequently observed in clinic, but its management remains as therapeutic challenge. The innervation of the cornea is provided by sensitive neurons located in the ophthalmic branch of trigeminal ganglion (TG). We recently reported that increasing endogenous enkephalin levels reduced ocular pain in a opioid receptor‐mediated manner (Reaux‐Le Goazigo et al., 2019). As the expression of the mu opioid receptor (MOR) in the cornea and TG is not known, this work aims to study MOR distribution both in control and under inflammatory pain conditions.MethodologyAdult male mice were submitted to a corneal scraping followed by 10 μL of lipopolysaccharide (LPS) at day 1 and day 3. Mechanical corneal sensitivity was measured by Von Frey filaments and corneal integrity was evaluated with in vivo confocal microscopy (IVCM). At D5, animals were perfused with 4% PFA to study the MOR expression by immunofluorescence (IF) and in situ hybridization (RNAscope method) in the ipsilateral cornea and TG. Images were captured with a confocal microscope and staining was quantified using imageJ.ResultsA corneal scraping and LPS instillation induced a mechanical corneal hypersensitivity compared to control mice. IVCM images showed a superficial epithelium alteration and inflammatory cells. IF experiments highlight the presence of MOR in corneal nerve fibers in both groups of animals but an increase of MOR immunoreactivity was noted in scraping + LPS mice. At the level of the ophthalmic branch of TG, MOR (protein and mRNA) was detected in a large population of primary sensory neurons. Quantification of MOR mRNA signal revealed a significant (+60%) increase of the receptor following corneal pain.ConclusionThis study provides novel information about the distribution of MOR in the cornea and TG in control and under corneal pain condition. Altogether, these results suggest that MOR could constitute a new therapeutic target for inflammatory ocular pain.