神经病理性痛伴发负性情绪时内侧前额叶皮质NR1的表达及磷酸化改变  

Alterations of NR1 expression and phosphorylation in the medial prefrontal cortex during neuropathic pain accompanied by negative emotions

作　　者：田志成 曹紫萱 李娟 王菲 刘可欣[2,3] 徐蕾 李海涛 罗鹏 罗层 蒋晓帆 TIAN Zhicheng;CAO Zixuan;LI Juan;WANG Fei;LIU Kexin;XU Lei;LI Haitao;LUO Peng;LUO Ceng;JIANG Xiaofan(Department of Neurosurgery,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;Department of Neurobiology,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China;No.6 Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China;No.4 Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学西京医院神经外科,陕西西安710032 [2]空军军医大学基础医学院神经生物学教研室,陕西西安710032 [3]空军军医大学基础医学院学员六大队,陕西西安710032 [4]陕西中医药大学,陕西咸阳712046 [5]空军军医大学基础医学院学员四大队,陕西西安710032

出　　处：《空军军医大学学报》2023年第11期1027-1033,共7页Journal of Air Force Medical University

基　　金：国家自然科学基金(82171363,82171458,32071002);国家自然科学基金青年科学基金(82201370);陕西省创新能力支撑计划项目(2022TD-49);陕西省创新人才推进计划青年科技新星项目(2021KJXX-19)。

摘　　要：目的研究在神经病理性痛伴发负性情绪的条件下,内侧前额叶皮质(mPFC)脑区中N甲基D天冬氨酸受体(NMDARs)的NR1亚基的表达和磷酸化的变化,为探究NR1参与慢性痛伴发负性情绪的发生发展提供理论依据。方法采用C57BL/6雄性小鼠进行选择性坐骨神经损伤造模(SNI组)或假手术处理(Sham组),造模7、28 d分别进行痛行为检测,造模后28 d进行旷场实验、高架十字迷宫实验和悬尾实验。随后取小鼠mPFC脑区蛋白,采用Western blotting、免疫荧光染色对NR1表达和磷酸化进行测定。结果与Sham组相比,SNI组小鼠在7 d和28 d的机械和热痛阈均下降,且在28 d出现焦虑样和抑郁样行为,以及NR1磷酸化水平显著上调。结论在神经病理性痛伴发负性情绪的条件下,mPFC脑区中NMDARs的NR1亚基磷酸化显著上调,提示mPFC脑区的NR1可能参与到慢性痛伴发负性情绪的发生发展中。Objective To study alterations of the NR1 subunit of N-methyl-D-aspartate receptors(NMDARs)in the expression and phosphorylation in medial prefrontal cortex(mPFC)brain region under the condition of neuropathic pain accompanied by negative emotions,and to provide a theoretical basis for exploring the involvement of NR1 in the occurrence and development of chronic pain accompanied by negative emotions.Methods Spared nerve injury modeling(SNI group)or Sham group were performed in C57BL/6 male mice.Pain behaviors were detected at 7 and 28 d after modeling,and open field test,elevated plus maze test,and tail suspension test were detected at 28 d after modeling.Subsequently,proteins in mPFC brain region of mice were taken for the determination of NR1 expression and phosphorylation by Western blotting and immunofluorescence staining.Results Compared with the Sham group,SNI mice had decreased mechanical and thermal pain thresholds at 7 and 28 d and showed anxiety-and depression-like behaviors at 28 d,as well as significant upregulation of NR1 phosphorylation.Conclusion Under the condition of neuropathic pain accompanied by negative emotions,the phosphorylation of NR1 subunit of NMDARs in mPFC brain region was significantly upregulated,suggesting that NR1 in mPFC brain region may be involved in the occurrence and development of chronic pain accompanied by negative emotions.

关 键 词：神经病理性痛 痛觉敏化 焦虑 抑郁 NMDA受体 

分 类 号：R741[医药卫生—神经病学与精神病学]