Abstract: Abstract: Objective To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2)-autophagy pathway on the incisional pain-remifentanil-induced hyperalgesia of rat model. Methods Twenty-four male Sprague-Dawley rats were randomly allocated into three groups: saline+incisional pain group (group I), remifentanil+incisional pain group (group RI) and Nrf2 agonist t-BHQ group (group tBHQ), with 8 rats in each group. In group I and RI, normal saline at 0.1 mL/(kg· min) and remifentanilat 1 μg/(kg·min) were respectively infused into caudal vein for 60 min. Rats in group t-BHQ were injected intraperitoneally with Nrf2 agonist t-BHQ (15 mg/kg), the first time at 0.5 h before remifentanil infusion, per 12 h once, 4 times in a row, the rest management was the same as group RI. Brennan incision pain model rats were constructed along with the infusions in the three groups. The thermal paw withdraw latency (PWL) and mechanical paw withdraw threshold (PWT) were measured at 24 h before the infusion (T0) and at 2 h (T1), 6 h (T2), 24 h (T3), 48 h (T4) after the infusion. Rats were sacrificed after the tests, then the L4-6 segments of signal cord were removed and the expression levels of autophagy-related proteins, microtubule associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ), Beclin 1, Nrf2 and Nrf2 downstream molecular hemeoxygenase-1 (HO-1) were detected by Western blot assay. Results The PWT and PWL values were decreased significantly with the prolongation of the processing time in the three groups. Compared with group I, PWL and PWT values were decreased at T1-4, the expression levels of LC3Ⅱ and Beclin-1 were increased while Nrf2 and HO-1 were decreased at T in group RI ( 0.05). While compared with group RI, PWL and PWT values were increased, and the expressions of Nrf2 and HO-1 were increased, LC3Ⅱ and Beclin-1 protein were upregulated in group tBHQ (P＜0.05). Conclusion The activation of Nrf2-autophagy pathway can improve the incisional pain- remifentanil induced hyperalgesia.

Key words: Key words: remifentanil, hyperalgesia, spinal cord, autophagy, incisional pain, Nrf2, t-BHQ