2023 HARVARD OPHTHALMOLOGY ANNUAL MEETING AND ALUMNI REUNION Candidate: Amir Naderi Poster #: C8 Effect of Neurokinin 1 Receptor Antagonist on Pain Response in Corneal Alkali Burn Amirreza Naderi, Hideaki Someya, Aytan Musayeva, Shudan Wang, Francesca Kahale, Akitomo Narimatsu, Yihe Chen, Reza Dana Purpose: Patients with ocular chemical burns have been reported to experience significantly lower quality of life compared to other ocular diseases. Chronic ocular pain is a significant morbidity even in well-healed eyes or cases with only corneal injury. Substance P (SP) is a well-known modulator of pain and was shown to modulate nociception in murine cornea. The purpose of this study was to determine whether the inhibition of SP can reduce ocular pain following chemical injury to the cornea by local antagonism of SP’s preferred receptor, neurokinin 1 receptor (NK1R). Methods: Corneal alkali burn was induced in C57BL/6 mice by means of a paper disc (2-mm diameter) soaked in 1 N NaOH for 10 seconds. 6 mice with 1:1 gender ratio were used for each experiment. SP levels in the cornea and trigeminal ganglion (TG) were measured by ELISA at 4, 7, 14, 21, and 28 days after alkali burn induction. Animals were randomized into two groups receiving L-733,060 (1μg/μl) or phosphate-buffered (PBS), topically twice a day for 4 weeks after alkali burn induction. On day 4, 7, 14, 21 and 28, eye wiping test (EWT) was performed to evaluate hyperalgesia after applying hypertonic saline (2M NaCl) as noxious stimulus. Following EWT, allodynia was assessed by quantifying palpebral ratio (PR) via an automated video analysis of the animals’ eye after instillation of a saline solution isoosmolar to tears (0.9 % NaCl) as neutral stimulus. Results: The SP protein levels in the corneas at 4, 7, 14, 21, and 28 days after alkali burn were 4732 ± 812, 6360 ± 1044, 6268 ± 425, 6238 ± 1701, and 5572 ± 323 pg/mg, respectively. Compared with the SP level of naive corneas (4077 ± 241 pg/mg), there were significant increases in the SP levels of the corneas on days 7, 14, 21, and 28 after alkali burn (P < 0.001, P < 0.001, P < 0.001, P < 0.01, respectively). Eye wipe behavior was significantly higher in PBS group compared to normal mice at 4, 7, 14, 21, and 28 days after alkali burn. L-733,060 group showed significant decreases in the behavior compared to PBS group at day 4, 14, 21, 28 (P < 0.01, P < 0.01, P < 0.01, P < 0.05, respectively). PR was significantly lower in PBS group compared to normal mice at 4, 7, 14, 21, and 28 days after alkali burn. L-733,060 group showed significant increases in PR at day 4, 14, 21, 28 (P < 0.01, P < 0.01, P < 0.01, P < 0.05, respectively). Conclusions: Our data demonstrate that NK1R antagonist reduces ocular pain response in a murine alkali burn model, suggesting SP blockade as a new therapeutic strategy in the management of ocular pain.