Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation

作     者：Ming Zhang Cong Li Qian Xue Chang-Bo Lu Huan Zhao Fan-Cheng Meng Ying Zhang Sheng-Xi Wu Yan Zhang Hui Xu 

作者机构：Department of Neurobiology and Collaborative Innovation Center for Brain ScienceSchool of Basic MedicineThe Fourth Military Medical UniversityXi’an710032China Department of AnesthesiologyHeze Municipal HospitalHeze274031China Department of Cardiovascular SurgeryXi’an International Medical Center HospitalXi’an710100China Department of Basic Medical LaboratoryThe General Hospital of Western Theater CommandChengdu610083China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2023年第39卷第9期

页      面：1348-1362页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(32271056,81671081,and 81701095) University Science and Technology Fund Planning Projects(2022XC002 and 2019XB006). 

主　　题：Rostral agranular insular cortex:Cannabinoid receptor 1-Neuropathic pain Dorsolateral fasciculus:GABAergic neuron 

摘      要：The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain state.Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve(CPN)ligation.The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral methods.The E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice.Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice.The analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the RAIC.Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.