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 significan 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.
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