Effects of intrathecal injection of different dose of protein kinase B inhibitor IV on hyperalgesia induced by remifentanil

Abstract

Objective To investigate the role and mechanism of protein kinase B (Akt) in opioid-induced hyperalgesia (OIH) with an incisional pain model.Methods Sixty C57BL/6 male mice were randomly divided into 5 groups (n=12):incision pain+ dimethyl sulfoxide(DMSO) group(group Ⅰ),incision pain+remifentanil+DMSO group(group R),Akt inhibitor Ⅳ 0.08 μg/10 μl group(group A1),Akt inhibitor Ⅳ 0.16 μg/10 μl group(group A2) and Akt inhibitor Ⅳ 0.32 μg/10 μl group(group A3).DMSO was the solvent of Akt inhibitor Ⅳ.Incisional pain model was made in the right paw of all the mice.In group R and group A1,A2,A3,subcutaneous remifentanil(0.04 mg/kg) was infused for 30 min while the surgery was being performed and intrathecal 10 μl DMSO(10％) with corresponding concentration of the Akt inhibitor Ⅳ 10 μl was injected respectively.The paw mechanical withdrawal threshold (PMWT) and the paw withdrawal thermal latency(PWTL) was tested at 1 d(T0) before and 6 h(T1),1(T2),2(T3),3(T4),5(T5),7 d(T6) after surgery.Results Compared with group Ⅰ and the baseline value,PMWT and PWTL were significantly decreased after surgery except 7 d in group R and all group A(P＜0.05).Compared with group R,PMWT[(5.03±0.62),(6.10±0.86),(5.92±0.88),(6.01±1.02) g.(4.07±0.79),(4.73±0.48),(4.77±0.59),(4.86±0.56) g.(5.05±0.75),(5.99±0.63),(5.99±0.71),(6.00±0.81) g] and PWTL[(0.48±0.06),(0.60±0.08),(0.61±0.07),(0.58±0.04) s.(0.38±0.07),(0.50±0.08),(0.48±0.06),(0.45±0.08) s.(0.37±0.09),(0.52±0.09),(0.49±0.12),(0.58±0.21) s] were significantly increased after surgery except 7 d in groups A1,A2,A3 (P＜0.05).While there was no significant difference among group A1,A2 and A3 (P＞0.05).Conclusions Intrathecal injection of different doses of Akt inhibitor Ⅳ effectively alleviates hyperalgesia induced by remifentanil in non-dose-dependent way. Key words: Protein kinase B; Protein kinase B inhibitor Ⅳ; Remifentanil; Hyperalgesia