Fig. 4

Y-25130 dose-dependently reversed the hyperalgesia after delayed REOI but transiently reversed PEOI-induced hyperalgesia. A Schematic diagram of the experimental time course of HWT measurements. The rats received adaption on days 4–6 prior to EOI application. Baseline HWT was obtained by measuring the average HWTs for 3 consecutive days before EOI application. REOI and PEOI models were established from day 0. On days 8–13, rats received consecutive i.t. microinjections of aCSF or 5-HT3 receptor antagonist Y-25130. HWTs related to mechanical stimulation of ipsilateral and contralateral orofacial sides (n = 6 per group) were measured at different time points. B Changes in ipsilateral and contralateral HWTs in REOI rats injected with 48, 24, 4.8 μg Y-25130, or aCSF. Injection of 48, 24, and 4.8 μg Y-25130 dose-dependently reversed the reduced HWTs in REOI rats. Results represent mean ± SD; three-way repeated measures ANOVA, followed by Tukey’s multiple-comparison test. P < 0.001, for days 13, 14, 16, 18, and 21 vs. baseline in the REOI/aCSF group. ** P < 0.01, *** P < 0.001, the REOI/48 μg Y-25130 group vs. the REOI/aCSF group. £ P < 0.05, ££ P < 0.01, the REOI/24 μg Y-25130 group vs. the REOI/aCSF group. && P < 0.01, the REOI/4.8 μg Y-25130 group vs. the REOI/aCSF group. C Changes in ipsilateral and contralateral HWTs in PEOI rats injected with 48 μg Y-25130 or aCSF and sham rats injected with 48 μg Y-25130. Injection of 48 μg Y-25130 only transiently reversed the reduced HWTs in PEOI rats. Results represent mean ± SD; three-way repeated measures ANOVA, followed by Tukey’s multiple-comparison test. P < 0.001, for days 13, 14, 16, 18, and 21 vs. baseline in the PEOI/aCSF group. # P < 0.05, ## P < 0.01, ### P < 0.001, the PEOI/48 μg Y-25130 group vs. the PEOI/aCSF group. BL, baseline. HWT, head withdrawal threshold. Tph2, tryptophan hydroxylase 2