AUTHOR=Xu Zihang , Zhu Yangzhuangzhuang , Shen Jun , Su Lin , Hou Yifei , Liu Mingxi , Jiao Xiaoning , Chen Xiao , Zhu Shiguo , Lu Yechen , Yao Chao , Wang Lixin , Gong Chenyuan , Ma Zhenzhen , Zou Chunpu , Xu Jianguang 

TITLE=Pain Relief Dependent on IL-17–CD4+ T Cell–β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.596780

DOI=10.3389/fnins.2020.596780

ISSN=1662-453X

ABSTRACT=Background and purpose: Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL17-CD4+ T lymphocyte-β-endorphin axis. 
Methods: After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines and the population of lymphocytes associated were investigated.  CD4+T lymphocytes were either isolated, or depleted with anti-CD4 monoclonal antibody. The titers of IL17A, IFN-γ, and β-endorphin were examined. The markers of T lymphocytes, myeloid derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages and natural killer (NK) cells were  assessed. The activation of the NF-κB signaling pathway was tested. 
Results: The pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL17A in CD4+ T lymphocytes. The titer of IL17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted. 
Conclusions: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL17-CD4+T lymphocyte-β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.