Role of spinal glucocorticoid receptor in PI3K/Akt signaling pathway in rats with morphine tolerance / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of spinal glucocorticoid receptors (GR) in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signal pathway in rats with morphine tolerance.Methods Forty healthy male SD rats aged 8-10 weeks weighing 300-350 g in which intrathecal (IT) catheters were successfully implanted without complication were randomly divided into 4 groups (n =10 each)control group(group C) received IT injection of normal saline 10 μl twice a day for 7 consecutive days; morphine tolerance group(group M) received IT injection of morphine 10 μg twice a day for 7 consecutive days; dexamethasone (a GR agonist) group( group DEX)received IT injection of dexamethasone 4 μg 30 min before IT injection of morphine,twice a day for 7 consecutive days;RU38486(a GR blocker)group (group R) received IT injection of RU38486 2 μg 30 min before IT injection of morphine,twice a day for 7 consecutive days.Tail-flick test was measured once a day after first IT administration and 1 d after the end of IT administration,and the percentage of maximum possible antinociceptive effect (MPAE)was caculated.After the last measurem of tail-flick test,the spinal dorsal horns were removed for determination of PI3K,Caspase-3 expression and Akt activity.Results Morphine tolerance developed in groups M,DEX and R,but did not develop in group C.Compared with group C,Akt activity was decreased,PI3K expression was downregulated and Caspase-3 expression was up-regulated in group M (P ＜ 0.05).Compared with group M,MPAE and Akt activity were decreased,PI3K expression was down-regulated and Caspase-3 expression was up-regulated in group DEX,and MPAE and Akt activity were inecreased,PI3K expression was up-regulated and Caspase-3 expression was down-regulated in group R (P ＜ 0.05).Conclusion Spinal cord GR is involved in morphine tolerance by inhibiting PI3K/Akt signal pathway.