小鼠岛叶皮质5型代谢型谷氨酸受体对神经病理性疼痛的调控作用  

The regulatory effect of metabotropic glutamate receptor 5 in insular cortex to neuropathic pain in mice

作　　者：涂可 邱欣彤 杨日升 侯立朝 陈涛 Tu Ke;Qiu Xintong;Yang Rishertg;Hou Lichao;Chen Tao(Department of Anesthesiology and Perioperative Medicine,Xijing Hospital;Department of Human Anatomy and K.K Leung Brain Research Centre;The Student No.1 Brigade,Academy of Basic Medicine,The Fourth Military Medical University,Xi＇an 710032,China;Xiang＇an Hospital,Xiamen University,Xiamen 361101,China)

机构地区：[1]空军军医大学西京医院麻醉与围术期医学科,西安710032 [2]空军军医大学基础医学院人体解剖学教研室暨梁銶琚脑研究中心,西安710032 [3]空军军医大学基础医学院学员一旅,西安710032 [4]厦门大学附属翔安医院,厦门361101

出　　处：《神经解剖学杂志》2018年第4期427-432,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金项目(81671095;31371126);厦门大学校长基金(20720170106);陕西省科技攻关课题(2016YFJH2-04)

摘　　要：目的:通过保留性神经损伤(SNI)模型,探索神经病理性疼痛发生后,岛叶皮质(IC)中FOS蛋白和5型代谢型谷氨酸受体(m Glu R5)及其下游分子的表达变化,并观察对岛叶皮质局部应用m Glu R5激动剂DHPG和拮抗剂MPEP对动物疼痛行为的影响。方法:将健康成年的雄性C57BL/6小鼠随机分为SNI组和假手术组(Sham组),SNI组采用SNI模型制造神经病理性疼痛模型。造模后通过机械痛行为学检测造模是否成功,通过免疫荧光染色检测岛叶皮质FOS蛋白的表达变化,通过Western Blot检测小鼠IC中m Glu R5和下游分子p-ERK与PI3K的表达变化;通过埋管注射的方式向实验组与假手术组IC内给予m Glu R5拮抗剂MPEP与激动剂DHPG,观察两种药物对小鼠机械性痛行为的影响。结果:SNI术后,小鼠的机械性痛的痛阈出现明显下降,并可维持至术后4周。免疫荧光组织化学染色结果显示:与假手术组相比,SNI组小鼠在术后1、2周IC中FOS蛋白表达增加(P<0.05)。Western Blot检测岛叶皮质m Glu R5及其下游分子p-ERK、PI3K的表达结果显示:术后SNI组m Glu R5表达水平相比假手术组增高(P<0.05),SNI组p-ERK表达水平相比假手术组增高(P<0.05),而PI3K仅在第2周时出现升高(P<0.05)。IC内置管给予MPEP后假手术组小鼠痛阈出现下降(P<0.05),而给予DHPG后SNI组的痛阈出现升高(P<0.05)。结论:小鼠IC中m Glu R5参与神经病理性疼痛的发生或调控,并且IC中m Glu R5表现出抑制性作用。在SNI后m Glu R5出现保护性增高,而m Glu R5激动剂DHPG可起到镇痛作用。Objective：To investigate the change of FOS protein and metabotropic glutamate receptor 5（m Glu R5） and its downstream molecules expression in insular cortex（IC） after spared nerve injury（SNI） induced neuropathic pain.And to observe the influence of application of mGluR5 antagonist MPEP or agonist DHPG into IC to pain behavior.Methods：Healthy adult male C57 BL/6 mice were randomly divided into two groups：SNI group and Sham group.SNI group mice received a spared nerve injury operation.A mechanical pain behavior test was carried out to investigate whether the surgery was succeeded or not.FOS expression in IC was quantified through immunofluorescent staining.And the expression level of mGluR5 and its downstream molecules p-ERK and PI3 K were quantified through Western Blot.Through cannulas inserted in bilateral IC,DHPG or MPEP was injected into IC.Mechanical pain test was then performed to observe the influence of DHPG or MPEP to pain threshold.Results：After SNI,model animal showed a significant decrease in the pain threshold.Immunofluorescent staining showed that FOS-ir neurons in IC were increased after SNI operation（P〈0.05）.Western Blot showed that,compared with Sham group,SNI group IC mGluR5 expression increased after surgery（P〈0.05） and p-ERK expression also increased after surgery（P〈0.05）.However,PI3 K expression only increased in the 2 nd week after SNI surgery（P〈0.05）.Through cannulas inserted in bilateral IC,DHPG or MPEP was injected into IC.The pain threshold of Sham group decreased after injection of MPEP（P〈0.05）,while the pain threshold of SNI group increased after injection of DHPG（P〈0.05）.Conclusion：Mice mGluR5 in IC is involved in the occurring or regulation of neuropathic pain and showed an inhibitory effect.There was a protective increase in mGluR5 after SNI,while mGluR5 agonist DHPG showed an analgesic effect.

关 键 词：神经病理性疼痛 5型代谢型谷氨酸受体 岛叶皮质 DHPG MPEP 小鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]