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

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.

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.

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).

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.

These results suggest that BAY-776 may be a promising option for managing chronic ocular pain.