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. 2016 Jun 1;6:26894. doi: 10.1038/srep26894

Figure 7. 16-8 and 16-19 effectively attenuate formalin-evoked trigeminal irritant pain.

Figure 7

(A) Time-course of nocifensive behavior in WT mice following whisker-pad injection of 4% formalin. The mice were pre-injected (i.p., 10 mg/kg; 15 min before formalin) with GSK205, 16-8 or 16-19. Note effective reduction of nocifensive behavior in the late “neural” phase by compounds 16-8, 16-19, not by GSK205. (B) Cumulative response binned into 3 phases: acute phase (0–5 min), interphase (5–15 min), and late “neural” phase (15–45 min). Note significant reduction of nocifensive behavior in the late phase by 16-8, 16-19, not GSK205 (*P < 0.01 vs vehicle and GSK205, one-way ANOVA). (C) As in (A), but also including Trpv4−/− mice. Compounds were applied i.p. 15 min before formalin challenge, at 10 mg/kg except established TRPA1 blocker, A967079 (25 mg/kg). Previously-established attenuated nocifensive behavior in early and late phase in Trpv4−/− mice was recapped, which was reduced further by TRPA1 blocker, A967079. (D) As in (B), plus inclusion of Trpv4−/− mice. Robust effects of TRPA1-blocker, A967079, were mimicked equi-potently by 16-8 and 16-19 for early phase, and by 16-8 for late phase, partially by 16-19 for late phase. (A,C) show averaged behavioral metrics per time-point, bars in (B,D) represent mean ± SEM; for (D) *P < 0.05; #P < 0.005, one-way ANOVA; for all panels n = 5–8 mice/group.