调控内侧前额叶皮质向丘脑室旁核投射通路对小鼠痛信息传递的影响  

Effect of modulating the pathway from the medial prefrontal cortex to the thalamic paraventricular nucleus on pain transmission in mice

作　　者：朱柯桦 吴凤玲 孙寒雪 洪洁 陈思海 史娟 李云庆 ZHU Ke-hua;WU Feng-ling;SUN Han-xue;HONG Jie;CHEN Si-hai;SHI Juan;LI Yun-qing(Institute of Medical Research,Northwestern Polytechnical University,Xi’an 710072,China;Department of Anatomy,Histology and Embryology,K.K.Leung Brain Research Centre,School of Basic Medicine,Air Force Military Medical University,Xi’an 710032,China)

机构地区：[1]西北工业大学医学研究院,西安710072 [2]空军军医大学基础医学院人体解剖学与组织学胚胎学教研室,暨梁銶琚脑研究中心,西安710032

出　　处：《解剖学报》2024年第4期430-436,共7页Acta Anatomica Sinica

基　　金：国家自然科学基金(82130034,82221001,82071253)。

摘　　要：目的探讨小鼠内侧前额叶皮质(mPFC)-丘脑室旁核(PVT)通路的投射神经元的性质及调控该通路对生理痛和急性痛的影响。方法谷氨酸脱羧酶67-绿色荧光蛋白(GAD67-GFP)基因敲入小鼠3只,用于形态学追踪实验,C57小鼠27只,用于行为学观察实验。将霍乱毒素B亚基(CTB)注入GAD67-GFP转基因小鼠的PVT内,观察向PVT投射的mPFC神经元的性质,使用化学遗传学方法调控mPFC-PVT通路,观察其对小鼠机械痛、热痛、冷痛以及辣椒素诱导的急性炎性痛的影响。结果mPFC内CTB标记神经元主要分布于Ⅴ层和Ⅵ层,且与GAD67-GFP不共标;化学遗传学方法激活mPFC-PVT通路可显著降低小鼠的机械痛阈值(P<0.0001),缩小热痛潜伏期(P<0.001),对冷痛无明显的影响;抑制此通路则可显著提高动物的机械性痛阈(P<0.05);辣椒素诱导急性炎性痛模型下激活此通路引起小鼠舔爪时间增加(P<0.05)。结论mPFC-PVT通路为非γ-氨基丁酸(GABA)能的神经通路,激活该通路可促进小鼠的机械痛、热痛和急性炎性痛反应。Objective To explore the property of projection neurons in the pathway from the medial prefrontal cortex(mPFC)to the thalamic paraventricular nucleus(PVT)and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice.Methods Three knock-in mice with glutamate decarboxylase 67-green fluorescent protein(GAD67-GFP)were used in morphological tracing experiments,and twenty-seven C57 mice were used for behavioral observation experiments.Cholera toxin subunit B(CTB)was injected into the PVT of GAD67-GFP transgenic mice,and the properties of mPFC neurons projected to PVT were observed.The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain,such as mechanical pain,thermal pain,cold pain,and on acute inflammatory pain induced by capsaicin in mice.Results CTB-labeled neurons in the mPFC were mainly distributed in layerⅤand layerⅥand not double-labeled with GAD67-GFP.Chemogenetic activation of the mPFC-PVT pathway decreased the mechanical pain threshold significantly(P<0.0001)and shortened the thermal pain latency(P<0.001),but had no obvious effects on cold pain.Inhibition of this pathway increased the mechanical pain threshold significantly(P<0.05).Activation of the pathway increased the paw licking time(P<0.05)in acute inflammatory pain induced by capsaicin.Conclusion mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain,thermal pain,and acute inflammatory pain induced by capsaicin in mice.

关 键 词：内侧前额叶皮质 丘脑室旁核 生理痛 急性炎性痛 化学遗传学 小鼠 

分 类 号：R322[医药卫生—人体解剖和组织胚胎学]