电针通过调节小鼠腹外侧眶皮层中谷氨酸能神经元缓解神经病理性疼痛诱发的焦虑和抑郁样行为  

Electroacupuncture relieves neuropathic pain-induced anxio-depression-like behaviors by regulating glutamatergic neurons in the ventrolateral orbital cortex of mice

作　　者：高佳佳 刁志君 袁伟 薛思梦 杨晓航 吴宇蔚 乔海法 GAO Jia-jia;DIAO Zhi-jun;YUAN Wei;XUE Si-meng;YANG Xiao-hang;WU Yu-wei;QIAO Hai-fa(College of Acupuncture-moxibustion and Tuina,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi Province,China;Traditional Chinese Medicine Master Research Institute,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi Province;Xianyang Key Laboratory of Neurobiology(Acupuncture),Xianyang 712046,Shaanxi Province)

机构地区：[1]陕西中医药大学针灸推拿学院,陕西咸阳712046 [2]陕西中医药大学国医大师研究院,陕西咸阳712046 [3]陕西省咸阳市神经生物学(针灸)重点实验室,陕西咸阳712046

出　　处：《针刺研究》2025年第1期3-13,共11页Acupuncture Research

基　　金：国家自然科学基金项目(No.82205263);陕西省科技厅自然科学基础研究计划项目(No.2019JM-399)。

摘　　要：目的:探讨电针“阳陵泉”“悬钟”能否缓解神经病理性疼痛诱发的焦虑和抑郁样行为,以及其机制是否与腹外侧眶皮层(VLO)中谷氨酸能神经元有关。方法:用腓总神经结扎(CPNL)法建立神经病理性疼痛小鼠模型。选取“阳陵泉”“悬钟”进行电针干预,每次15 min,每日1次,共7 d。VLO注射rAAVVGLUT1-CRE-WPREs和rAAV-Ef1a-DIO-hM3Dq-mCherry-WPREs或rAAV-Ef1a-DIO-hM4Di-mCherry-WPREs化学遗传病毒,腹腔注射氯氮平-N-氧化物(CNO)以特异调节VLO中谷氨酸能神经元的活动水平。使用足底触觉测痛仪和足底热痛觉测痛仪分别检测小鼠的机械缩足阈值(MWT)和热缩足潜伏期(PWL);通过旷场、高架十字迷宫、强迫游泳及悬尾等行为学实验检测小鼠的焦虑和抑郁样行为;免疫荧光染色法观察神经元激活与抑制水平。结果:与假手术组相比,CPNL组小鼠术后第3天的MWT和PWL显著降低(P<0.001),一直持续到第28天;与假手术组相比,CPNL组小鼠旷场实验中央区域停留时间显著减少(P<0.001),高架十字迷宫实验进入开臂次数和进入开臂时间显著减少(P<0.01,P<0.05),强迫游泳实验和悬尾实验不动时间显著增加(P<0.01,P<0.05);与CPNL组相比,CPNL+电针组小鼠焦虑和抑郁样行为均减轻(P<0.05,P<0.01,P<0.001)。与激活病毒+盐水组相比,激活病毒+CNO组小鼠的焦虑和抑郁样行为均减轻(P<0.05,P<0.01)。与抑制病毒+电针+盐水组相比,抑制病毒+电针+CNO组小鼠的焦虑和抑郁样行为均较严重(P<0.001,P<0.01,P<0.05)。结论:电针“阳陵泉”“悬钟”可能通过激活VLO中谷氨酸能神经元缓解神经病理性疼痛诱发的焦虑和抑郁样行为。Objective To investigate whether electroacupuncture(EA)at"Yanglingquan"(GV34)and"Xuanzhong"(GB34)canalleviateanxio-depression-likebehaviorsinducedby neuropathic painandwhethertheeffect of EA is in connection with the activity of glutamatergic neurons in the ventrolateral orbital cortex(VLO).Methods The neuropathic pain model was established by common peroneal nerve ligation(CPNL).GV34 and GB34 were selected in EA treatment(2 Hz/15 Hz,1 mA),15 min each time,once a day for 7 d.Chemogenetic mixture viruses rAAV-VGLUT1-CRE-WPREs and rAAV-Ef1a-DIO-hM3Dq-mCherry-WPREs or rAAV-Ef1a-DIO-hM4Di-mCherry-WPREs were injected into the VLO,respectively.Clozapine-N-oxide(CNO)wasinjectedintraperitoneally toregulatetheactivity of glutamatergic neurons in the VLO precisely.Mechanical withdrawal threshold(MWT)and paw withdrawal latency(PwL)were measured by dynamic plantar tactile instruments and plantar thermal nociceptor instruments.Anxio-depression-like behaviors were measured by behavioral tests,including open field test,elevated plus maze test,forced swimming test,and tail suspension test.The activation and inhibition levels of neurons were observed by immunofluorescence staining.Results Compared with the sham group,the MWT and PWL of CPNL mice were significantly decreased(P<0.001)on the 3rd day after surgery and lasted until the 28th day.After CPNL,the activity time spent in the central area of open field test reduced(P<0.001),the percentage of entries and activity time in the open arm of elevated plus maze test were significantly reduced(P<0.001,P<0.05);the immobile duration of forced swimming test and tail suspension test were remarkably prolonged(P<0.01,P<0.05)of mice in the CPNL group.However,after EA treatment,compared with the CPNL group,the anxio-depression-like behaviors of the mice were alleviated(P<0.05,P<0.01,P<0.001).Activating glutamatergic neurons of VLO produced an anti-anxio-depression effect(P<0.05,P<0.01)in neuropathic pain mice.Compared with the inhibited+EA+saline group,inhibiting glutamatergic neurons of VL

关 键 词：腹外侧眶皮层 神经病理性疼痛 谷氨酸能神经元 电针 焦虑和抑郁样行为 

分 类 号：R245.97[医药卫生—针灸推拿学]