Effect of ketamine and cionidine on P2X4 R mRNA expression in spinal cord in a rat model of neuropathic pain

Objective To evaluate the effect of ketamine and elonidine on P2X4R mRNA expression in the spinal cord in a rat model of neuropathic pain.Methods Eighty male SD rats weighing 180-220 g were randomly divided inte 5 groups (n = 16 each): sham operation group (group S),neuropathic pain group (group NP),ketamine group (group K),clonidine group (group CL) and ketamine + clonidine group (group KC).The animals were anesthetized with intraperitoneal chloral hydrate 400 mg/kg.The right sciatic nerve was exposed and four ligatures were placed on the sciatic nerve at 1 mm interval.In group S,the right sciatic nerve was exposed but not ligated,and in the other groups four ligatures were placed around the right sciatic nerve (chronic constrictive injury,CCI) as described by Bennett.The animals were injected intraperitoneally with ketamine 10 mg/kg,clonidine 1 mg/kg,and ketamine 5 mg/kg + clonidine 0.5 mg/kg in normal saline 2 ml in group K,CL and KC respectively,while normal saline 2 ml in group S and NP at 3-21 d after CCI.Mechanical and thermal pain threshold were measured by paw withdrawal latencies to run Frey hair and radiant heat stimulation at 1 d before and 3,7,14,21 d after CCI.Four animals were killed at 1 d before (baseline) and 7,14 and 21 d after CCI following the measurement of pain threshold in each group and the L4.5 segments of the spinal cord were removed for determination of P2X4 R mRNA expression by RT-PCR.Results There was no significant change in thermal and mechanical paln threshold and P2X4 R mRNA expression in the spinal cord after CCI in group S ( P > 0.05),while thermal and mechanical pain threshold was reduced,and P2X4 R mRNA expression was up-regulated in the other four groups as compared with the baseline values (P 0.05).Conclusion Both ketamine and clonidine can alleviate neuropathic pain via down-regulating the expression of P2X4 R mRNA in the spinal cord in a rat model of neuropathic pain. Key words: Ketamine; Clonidine; Neuralgia; Receptors,purinergic P2; Spinal cord