Effect of dexmedetomidine on expression of purinergic P2X4 receptor and p38 mitogen-activated protein kinase mRNA in spinal cord in a rat model of neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of dexmedetomidine on the expression of purinergic P2X4 receptor (P2X4R) mRNA and p38 mitogen-activated protein kinase (p38 MAPK) mRNA in spinal cord in a rat model of neuropathic pain (NP).Methods Seventy-two male SD rats weighing 180-220 g were randomly assigned into 3 groups ( n =24 each)sham operation group (group S),group NP and dexmedetomidine group ( group DEX).The animals were anesthetized with intraperitoneal 10％ choral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI).The right sciatic nerve was exposed and 4 ligatures were placed on sciatic nerve at 1 mm intervals with 4-0 silk thread in groups NP and DEX.In group S,the right sciatic nerve was only exposed but not ligated.Dexmedetomidine 50μg/kg was injected intraperitoneally daily staring from the end of operation,while the equal volume of normal saline was injected in groups S and NT.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured on day 1 before operation and on day 1,3,7 and 14 after operation.Six animals were sacrificed after MWT and TWL measurement on day 1,3,7 and 14 after operation in each group,the L4～6 segment of spinal cords was removed for determination of P2X4 R mRNA and p38 MAPK mRNA expression by RT-PCR.Results Compared with group S,MWT and TWL were significantly decreased and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly up-regulated after operation in groups NP and DEX ( P ＜0.05).Compared with group NP,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly down-regulated after operation in group DEX ( P ＜ 0.05 ).TWL and MWT were significantly higher and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly lower on day 1,3 and 14 after operation than on day 7 after operation in groups NiP and DEX ( P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine attenuates NP is related to inhibition of the expression of P2X4 R mRNA and p38 MAPK in rats.