Effect Of Dexmedetomidine And Ketamine On Expression Of P2X₇Purinergic Receptor And P2X₄Purinergic Receptor In Spinal Cord Of Rats With Neuropathic Pain

Objective:To investigate the analgesic effects of combined peritoneal injection of dexmedetomidine with ketamine on the chronic constriction iniury (CCI) in rats and to explore the effects of potential mechanism of neuropathic pain induced by P2X4R and P2X7R mRNA expression,which may provide the new method and basis for treatment.Methods:Ninety adult male Wistar rats weighing180～220g were randomly divided into5groups as follows:sham group(group S)、neuropathic pain group(group CCI)、ketamine group(group KET)、dexmedetomidine group (group DEX) and combined group(group DK). The animals were anesthetized with intraperitoneal10%chloral hydrate350mg/kg. Four ligatures were placed on right sciatic nerve at1mm intervals with4-0silk thread in group CCI、group KET、group DEX and group DK. Rats in group KET、group DEX and group DK were intraperitoneally injected respectively with dexmedetomidine50μg-kg-1、ketamine10mg-kg-1and dexmedetomidine25μg-kg-1+ketamine5mg·kg-1daily after CCI, while the same volume normal saline was in jected into group S and group CCI. Paw withdrawal threshold to mechanical stimulation with von Frey filament(MWT) and paw withdrawal latency to thermal stimulation(TWL) were measured on the1st day before and the3rd,7th and14th day after operation. Animals of three groups were killed at each time points after the measurement of MWT and TWL, Their lumbar segments(L4-6)were removed for measuring the expression of P2X4R and P2X7R mRNA by reverse transcription-polymerase chain reaction(RT-PCR)Results:Compared with group S, MWT and TWL were significantly decreased and the expression of P2X4R and P2X7R mRNA were significantly up-regulated after operation in group CCI、DEX、KET and DK (P<0.05). Compared with group CCI, TWL and MWT were significantly increased and the expression of P2X4R and P2X7RmRNA were significantly down-regulated after operation in group DK、D K(P<0.05). Compared with group DEX and KET, TWL and MWT were significantly increased and the expression of P2X4R and P2X7RmRNA were significantly down-regulated after operation in group DK (P<0.05).Conclusion:Peritoneal injection of dexmedetomidine and ketaraine can inhibit the development of mechanical allodynia and thermal hyperalgesia in the rat model of neuropathic pain, they can reduce the expression of P2X4R and P2X7R mRNA in rat and can also produce synergistic abirritation.