Fig 2: Continuous injection of cyclotraxin‐B into the insular cortex reduced chronic corneal pain‐induced corneal hypersensitivity and inhibited descending inflammatory factor upregulation. (A) Diagram and timeline schema of the experimental design. Gray arrows mark the local infusion of cyclotraxin‐B or saline into the insular cortex. Bilateral extraorbital glands were excised on day 0. Insular cortex cannula was inserted on day 21 after surgery. Dark gray circles mark behavior test including chemical and mechanical corneal sensitivity test. Black circles mark open field test. Light gray circles mark tissue sampling with qRT‐PCR. (B–E) The protein expression of TNFα, IL‐6, IL‐10, and IL‐1β in DE mice after consecutive administration of cyclotraxin‐B (10 μg/μL, 0.05 μL per side for 5 days) (n = 4, *p < 0.05 and **p < 0.01 vs. DE group). (F–L) Effect of treatment with BDNF antagonist cyclotraxin‐B induces a statistically significant antinociceptive effect in chemical and mechanical corneal sensitivity, whereas during anxiolytic effect is unremarkable. The DE + cyclotraxin‐B group represents that of dry eye mice receiving an intra‐insular cortical microinjection of cyclotraxin‐B (10 and 0.05 μL per side; MCE). (F–I) The chemical and mechanical thresholds after administration of cyclotraxin‐B in DE mice (n = 8, **p < 0.01, ***p < 0.001 and ****p < 0.0001 vs. DE + saline group). (J) Representative activity tracking OFT in Sham, DE, DE + cyclotraxin‐B, DE + saline mice. (K,L) Time in center region (K) and total distance traveled (L) during OFT (n = 6, ****p < 0.0001 vs. Sham group). CTB, cyclotraxin‐B; DE, dry eye; IL‐10, interleukin‐10; IL‐1β, interleukin‐1β; IL‐6, interleukin‐6; NS, normal saline; ns, not significant; OFT, open field test; QPCR, quantitative polymerase chain reaction; TNFα, tumor necrosis factor α.