Peripheral BDNF Regulates Somatosensory–Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain

作     者：Hang Xian Huan Guo Yuan-Ying Liu Jian-Lei Zhang Wen-Chao Hu Ming-Jun Yu Rui Zhao Rou-Gang Xie Hang Zhang Rui Cong 

作者机构：Department of OrthopedicsXijing HospitalThe Air Force Medical UniversityXi’an710032China Pain and Related Diseases Research LaboratoryMedical College of Shantou UniversityShantou515041China School of Life Science and Research Center for Resource Peptide DrugsShaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological ResourcesYanan UniversityYanan716000China Department of NeurobiologySchool of Basic MedicineThe Air Force Medical UniversityXi’an710032China The Sixth RegimentSchool of Basic MedicineThe Air Force Medical UniversityXi’an710032China The Tenth Squadron of the Third RegimentSchool of Basic MedicineThe Air Force Medical UniversityXi’an710032China 

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

年 卷 期：2023年第39卷第12期

页      面：1789-1806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)] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(82072526 82171212 and 81870867). 

主　　题：Brachial plexus avulsion Neuropathic pain Sympathetic nervous system Brain-derived neurotrophic factor Peripheral sensitization Mechanical allodynia 

摘      要：Brachial plexus avulsion(BPA)is a combined injury involving the central and peripheral nervous systems.Patients with BPA often experience severe neuropathic pain(NP)in the affected limb.NP is insensitive to the existing treatments,which makes it a challenge to researchers and clinicians.Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction,which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP.However,the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear.In this study,through using a novel BPA C7 root avulsion mouse model,we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased,and the markers of sympathetic nervous system activity includingα1 andα2 adrenergic receptors(α1-AR andα2-AR)also increased after BPA.The phenomenon of superexcitation of the sympathetic nervous system,including hypothermia and edema of the affected extremity,was also observed in BPA mice by using CatWalk gait analysis,an infrared thermometer,and an edema evaluation.Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice.Further,intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice.In another branch experiment,we also found the elevated expression of BDNF,TrκB,TH,α1-AR,andα2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry.Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP.This study also opens a novel analgesic target(BDNF)in the treatment of this pain with fewer complications,which has great potential for clinical transformation.