鞘内注射MK-801对骨癌痛小鼠的镇痛作用及脊髓NR2B蛋白表达的影响

目的探讨MK-801连续鞘内注射对骨癌痛小鼠的镇痛作用及脊髓背角N-甲基2-天冬氨酸亚基（NR2B）蛋白表达的影响。方法C3H／HeJ小鼠32只，随机分为4组（n=8）：正常对照组、假手术组、骨癌组＋生理盐水组、骨癌组＋MK-801组。分别测定术后9、12、15、18、21d小鼠机械缩腿阈值（MWT）和热缩腿潜伏期（TwL）；骨癌组＋生理盐水组、骨癌组＋MK-801组分别在肿瘤细胞种植后第10日鞘内给予MK-80110nmol／5μl和生理盐水5μl，每日1次，连续7日，采用免疫组织化学法检测各组脊髓背角NR2B蛋白表达的变化。结果骨癌组＋生理盐水组MWT与TwL显著下降，脊髓背角有大量NR2B阳性表达（P〈0．01）；骨癌组＋MK-801组仅出现轻度痛敏症状，NR2BmRNA表达受到明显抑制（P 〈0．01）。结论NR2B表达上调可能是骨癌痛的发病机制之一，MR-801组可抑制其表达从而发挥一定程度的镇痛作用。

Effects of analgesia and spinal NR2B express in murine model of bone cancer pain after MK-801 intrathecal injections

Objective To investigate the effect of MK-801,a NMDA receptor inhibitor,injected intratheeally （IT）on tactile allodynia and thermal hyperalgesia, and NR2B express in the spinal cord. Methods 32 C3H/HeJ mices were randomly divided into four groups （n=8）：normal, sham operation,bone cancer and NS group or MK-801 group, mechanical withdrawal threshold （MWT） and thermal withdrawal lantency （TWL） were determined with von Frey filaments and thermal radiation apparatus at 9,12,15,18,21 d respectively. NCTC2472 cells and NS was given respectively one time daily,in seven days at 10d after operation. NR2B was also detected using immunohistochemical methods. Results MWT and TWL in group of bone cancer and NS decreased significantly（P〈0.05 or P〈0.01）, NR2B protein expression in spinal dorsal horn were increased in the bone cancer group and NS group （P〈0.01） . MWT and TWI. did not change in MK-801 group,NR2B protein expression in spinal dorsal horn were significantly inhibited compared to NS group and bone cancer group. Conclusion NR2B receptor of the spinal is up-regulated in the neuropathic pain induced by intra-femur linoculations of osteolytic sarcoma cells. Intrathecal injection of MK-801 can alleviate tactile allodynia and thermal hyperalgesia induced by intra-femur linoculations of osteolytie sarcoma cells.