PURPOSE: Transient receptor potential subfamily V member 1 (TRPV1) is a non-selective cation channel that acts as a polymodal receptor and is highly expressed in corneal sensory neurons and corneal epithelial cells. TRPV1 responds to mechanical, thermal, and chemical stimuli and plays a key role in nociception and pain signaling. In this study, we tested the hypothesis that BL1332, a novel TRPV1 antagonist, suppresses acute pain behavior in a rat model of capsaicin-induced ocular pain in order to assess in vivo TRPV1 target engagement.

METHODS: Sprague Dawley rats received a corneal epithelial injury in the right eye (OD) using an Algerbrush. Capsaicin, a potent TRPV1 agonist, was then applied topically OD, and the number of eye wipes was recorded for 60 seconds. Thirty minutes after topical capsaicin application, rats received a topical dose of vehicle, 0.5% proparacaine, or BL1332 at one of four doses: 0.02%, 0.06%, 0.15%, or 0.3%. At 15 minutes, 30 minutes, or 6 hours post-treatment, rats received a second topical application of capsaicin OD, and the number of eye wipes was recorded for 60 seconds to assess pain suppression and duration of observed effect.

RESULTS: Across all BL1332 concentrations tested, a single instillation significantly suppressed capsaicin-induced pain behavior (number of eye wipes) at 30 minutes post-administration compared with vehicle (p<0.01). in contrast 0.5 proparacaine produced a significant reduction only at 15 minutes post-administration p><0.001). notably 0.3 bl1332 demonstrated pain suppression for 6 hours p="0.0004)," whereas 0.02 did not indicating a dose-dependent duration of action.>

CONCLUSIONS: Our study demonstrates that BL1332 robustly inhibits acute capsaicin-induced ocular pain response, with efficacy lasting at least 6 hours at sufficient concentration. These findings help confirm pharmacological activity and in vivo TRPV1 target engagement of BL1332 and support its development for ocular surface pain indications.