P2X4 Receptor Antagonist Ameliorates Ocular Pain in Rats After Lacrimal Gland Removal

PURPOSE: The purinergic receptor P2X4 is critical to transduction of ocular pain. The aim of this study was to investigate the therapeutic potential of the P2X4 receptor antagonist BAY-776 in alleviating chronic ocular pain. METHODS: Chronic ocular pain was induced in male rats (8-9 weeks old; n = 12 per group) via double lacrimal gland removal (DLGR). Rats were randomly assigned to receive vehicle control, 1.0 mg/mL BAY-776, or 2.5 mg/mL BAY-776 eyedrops after DLGR. Treatment efficacy was assessed with blink tests, wipe tests, and in vivo confocal microscopy (IVCM) at pre- and postsurgical baselines and 2 and 4 weeks of treatment. Corneal subbasal nerve plexus (SNP) density and inflammatory cells were quantified by IVCM image analysis and immunohistochemical staining. Efficacies of 2.5 mg/mL BAY-776 and 0.05% cyclosporine were also compared. RESULTS: Compared with vehicle control, BAY-776 at both concentrations significantly reduced wipe and blink responses (P < 0.01). BAY-776 mitigated the increases in corneal SNP and inflammatory cell density after DLGR (P < 0.01). Notably, BAY-776 at 2.5 mg/mL reduced wipe test scores and inflammatory cell density at levels comparable to those of 0.05% cyclosporine (P < 0.001). Although cyclosporine did not significantly affect the blink test compared with vehicle, it reduced SNP density compared with BAY-776 (P < 0.05). CONCLUSIONS: The results indicate that BAY-776 effectively reduced chronic ocular pain in rats, showing efficacy similar to that of cyclosporine and underscoring its therapeutic potential for managing ocular pain. TRANSLATIONAL RELEVANCE: These results suggest that BAY-776 may be a promising option for managing chronic ocular pain.