摘要
目的:研究氯胺酮对神经病理性疼痛大鼠脊髓P2X4受体mRNA表达的影响。方法:雄性SD大鼠45只,体重180-220g,随机分为假手术组(S组)、对照组(C组)和氯胺酮Ⅰ、Ⅱ、Ⅲ组(KⅠ、Ⅱ、Ⅲ组),每组9只。S组大鼠仅分离坐骨神经但不结扎,其余组建立坐骨神经慢性压迫性损伤(CCI)模型,KⅠ、Ⅱ、Ⅲ组分别于CCI后3d开始至取材点每天腹腔注射氯胺酮5mg/kg、10mg/kg、20mg/kg;S组和C组注射相同体积的生理盐水。各组大鼠分别于术前1d,术后3d、7d、14d、21d测定大鼠机械性痛觉过敏(MWT)和热痛觉过敏(TWL)。各组均分别于CCI术后7d、14d、21d取3只大鼠,测定痛阈后处死,取L4~5脊髓组织,用逆转录PCR(RT-PCR)方法测定P2X4受体mR-NA表达水平。结果:与术前及S组比较,C组、KⅠ、Ⅱ、Ⅲ组术后3d开始热痛阈及机械痛阈显著降低(P〈0.05)。与C组比较,KⅠ、Ⅱ、Ⅲ组术后7d,14d,21d热痛阈及机械痛阈显著升高(P〈0.05)。与S组比较,C组、KⅠ、Ⅱ、Ⅲ组大鼠脊髓P2X4受体表达在术后7d、14d、21d均显著增加(P〈0.05);与C组大鼠比较,KⅠ、Ⅱ、Ⅲ组脊髓P2X4受体表达明显减少(P〈0.05)。结论:腹腔注射氯胺酮可抑制慢性神经痛大鼠痛觉过敏,该作用可能是通过作用于P2X4受体介导的。
Objective: To investigate the effects of ketamine on chronic constriction injury(CCI) induced neuropathic pain in rats,and to explore the potential mechanism of P2X4 receptor underlying it.Methods: forty five male SD rats weighing 180~220g were randomly divided into 5 groups as follows(n=9 each): sham operation group(S),CCI group(C) and ketamine groupⅠ,Ⅱ,Ⅲ(KⅠ,Ⅱ,Ⅲ).In group S,the right sciatic nerves were exposed but not ligated,and in other groups four ligatures were placed around the right sciatic nerve according to the methods of Bennett.From the third day after operation,5 mg/kg,10 mg/kg and 20mg/kg ketamine were injection intraperitoneally into group KⅠ,Ⅱ,Ⅲ respectively and the same volume normal saline was injection into S and C group once a day.Mechanical and thermal pain threshold were measured by paw withdrawal latencies to von Frey hair and radiant heat stimulation at 1 d before operation and 3d,7d,14d,21 d after operation.Three animals were killed at 7d,14d and 21 d after the pain threshold was measured in all groups respectively and the L4~5 segment of the spinal cord was removed.Reversal transcript-polymerase chain reaction(RT-PCR) was used to evaluate the transcription of P2X4 receptor.Results: TWL and MWT of group C,KⅠ,Ⅱ,Ⅲ were markedly reduced at 3d after operation than those before operation and group S(P0.05).TWL and MWT of group KⅠ,Ⅱ,Ⅲ at 7d,14d,21d after operation were increased significantly compared with group C(P0.05).The expression of P2X4 mRNA in group C,KⅠ,Ⅱ,Ⅲ at 7d,14d,21d after operation was increased significantly compared with group S(P〈0.05).The expression of P2X4 mRNA in group KⅠ,Ⅱ,Ⅲ was decreased significantly compared with group C(P0.05).Conclusion: Intraperitoneal administration of ketamine reduces hyperalgesia on chronic neuralgia of rats,and the underlying mechanism was correlated with the decreasing expression of P2X4 receptor in the spinal cord dorsal horn.
出处
《中国疼痛医学杂志》
CAS
CSCD
2010年第1期30-33,共4页
Chinese Journal of Pain Medicine