大鼠脊髓背角内吗啡肽2的表达与骨癌痛的相关性  

Relationship between the expression of endomorphin-2 in spinal dorsal horn in rats and bone cancer pain

作　　者：牛乐 岳江涛 冯凯隆 梅江涛 贾晓康 戴先文 NIU Le;YUE Jiangtao;FENG Kailong;MEI Jiangtao;JIA Xiaokang;DAI Xianwen(Department of Orthopaedics, Xi'an Chang'an Hospital, Xi'an 710000, China)

机构地区：[1]西安市长安医院骨科,陕西西安710016

出　　处：《西部医学》2021年第12期1742-1746,共5页Medical Journal of West China

基　　金：国家自然科学基金(81400991)。

摘　　要：目的观察骨癌痛大鼠脊髓背角内吗啡肽2(EM2)的表达变化及其与痛行为的相关性。方法30只SD大鼠随机分为骨癌痛(BCP)组、假手术(sham)组和空白对照组,每组各10只。BCP组在大鼠胫骨上端骨髓腔内注入Walker256癌细胞造模,sham组在胫骨相同部位注射等量生理盐水,空白对照组未经任何处理。每组在造模前和造模后3、5、7、10、14、17、21 d先进行痛觉行为检测,然后利用高效液相色谱法和免疫组化染色检测脊髓EM2的表达变化。在BCP大鼠痛觉阈值最低的时间点进行行为药理学检测,即经脊髓鞘内注入不同剂量的吗啡、EM2或μ型阿片受体拮抗剂β-FNA,然后记录痛觉阈值的变化。结果与sham组和空白对照组对比,BCP组在造模后5天痛觉阈值显著降低,14天时痛觉阈值达到最低点(P<0.05),BCP组脊髓背角EM2表达量和染色密度显著减少(P<0.05),EM2的表达减少与痛觉阈值的降低呈显著正相关(P<0.001,r=0.963);BCP组鞘内给予吗啡和EM2均能剂量依赖地镇痛,但EM2镇痛作用比吗啡强,而鞘内给予β-FNA易化疼痛。结论脊髓背角EM2的表达下调导致了BCP大鼠痛敏状态的形成,从全新的角度诠释BCP形成的病理生理机制,为BCP诊疗提供了新的理论依据。Objective To observe the expression of endomorphin-2(EM2)in spinal dorsal horn of bone cancer pain(BCP)rat model and explore its relationship with pain behavior.Methods Adult male SD rats were randomly divided into BCP group,sham operation group and naive group.While Walker-256 cancer cells were injected into the bone marrow cavity of the upper tibia in BCP group.The sham group were treated with the same amount of normal saline.At different time points after cancer cell injection(0d,3d,5d,7d,10d,14d,17d and 21d),the pain behavior of each group was detected,and then EM2 was analyzed by immunohistochemistry and high performance liquid chromatography.In BCP group,the mu-opioid receptor antagonistβ-FNA,morphin or EM2 was injected intrathecally when the threshold of paw withdrawal reached the lowest value.Pain behavior was measured immediately after injection.Results Compared with the sham group and naive group,the paw withdrawal threshold of BCP group decreased significantly on the 5th day after injection and reached the lowest value on the 14th day(n=10/group;P<0.05).In BCP group,the immunohistochemical staining and the expression of EM2 in spinal dorsal horn were significantly decreased(P<0.05).The decrease of EM2 expression level in BCP group was significantly correlated with the decrease of paw withdrawal threshold(P<0.001,r=0.963).The analgesic effect of intrathecal injection of EM2 was stronger than that of morphine in BCP group.However,intrathecal injection ofβ-FNA promoted pain behavior.Conclusion Our findings suggest that the decrease of spinal EM2 contributes to the loss of endogenous analgesia and the enhancement of pain transmission in BCP.

关 键 词：骨肿瘤 骨癌痛 阿片肽 内吗啡肽2 

分 类 号：R730.6[医药卫生—肿瘤] R738[医药卫生—临床医学]