Fig. 1

MJN110 dose dependently alleviated periorbital allodynia and reduced persistent pain sensitivity in the mTBI mice. The timeline and various experimental procedures were illustrated in Fig. 1A. von Frey (vF) test, mass spectrometry (MS), PCR and immunohistochemistry (IHC) were performed at the times indicated (A). On days 5 and 7 post-injury, the TBI/vehicle group showed a significantly reduced periorbital tactile threshold compared to the sham group (B). Animals treated with low dose of MJN110 (MJN, 1 mg/kg) displayed similar mechanical response as the TBI/vehicle animals. At 2.5 mg/kg, MJN increased mechanical thresholds on day 5 and day 7 post-injury compared to the TBI/vehicle group. **, p < 0.01 was obtained when the MJN treated group was compared to the TBI/vehicle group (n = 15/group). #, p < 0.05, ##, p < 0.01 was obtained when the TBI/vehicle group was compared to the sham group (n = 15/group). The righting reflex latency (RRL) was recorded after each impact (C). Compared to the sham group, both TBI/vehicle and MJN treatment groups showed longer RRL. No difference was found between the TBI/vehicle and MJN treated groups. CGRP (0.01 mg/kg) was given on day 33 and day 45 post-injury to the sham, TBI/vehicle and MJN treated groups and periorbital allodynia was assessed (D). There was no pain sensitivity change in both sham and the MJN treated groups, but the TBI/vehicle group exhibited significantly increased pain sensitivity compared to the sham and the MJN treatment group. *, p < 0.05 was obtained when the MJN treated group was compared to the TBI/vehicle group (n = 12/group). #, p < 0.05, and ##, p < 0.01 were obtained when the TBI/vehicle group was compared to sham group (n = 12/group)