Nrf2 Activation Attenuates Chronic Constriction Injury-Induced Neuropathic Pain via Induction of PGC-1α-Mediated Mitochondrial Biogenesis in the Spinal Cord

Figure 1

Effect of RTA-408 on the treatment and prevention of mechanical pain and hyperalgesia after chronic constriction injury (CCI). (a, b) Mechanical allodynia and thermal hyperalgesia were used to detect the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL). PWL and PWT were conducted before CCI (day 0) and at day 1, day 3, day 7, and day 14 after surgery (, , and compared with the sham group, per group). (c, d) A single injection of RTA-408 (RTA, 1 μg, 5 μg, and 10 μg/5 μL, i.t.) or vehicle (5 μL) was given on day 7 following CCI (, , and compared with the CCI+vehicle group, ^### compared with the group treated with RTA-408 (5 μg)). In contrast, the CCI+vehicle group had no significant change in PWT and TWL (^### compared with the sham+vehicle group). No significant difference in the baseline thresholds was observed among all groups ( per group). (e, f) RTA-408 (1 μg, 5 μg, and 10 μg/5 μL, i.t.) or vehicle (5 μL) was given for 5 consecutive days from day 7 to day 11 ( compared with the CCI+vehicle group, ^#, ^##, and ^### compared with the group treated with RTA-408 (5 μg)). In contrast, the CCI+vehicle group had no significant change in PWT and TWL (^### compared with the sham+vehicle group) ( per group). (g, h) Preventive effect of RTA-408 on the development of pain hypersensitivity following CCI. RTA-408 (10 μg, i.t.) was given once daily from day 0 to day 2 after CCI. The pain behavioral tests were performed before CCI and on day 1, day 3, day 7, and day 14 after CCI. Two-way ANOVA with repeated measures was performed, followed by the Bonferroni post hoc test ( compared with CCI+vehicle mice, per group).

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