Zihang Xu1, Yangzhuangzhuang Zhu1, Jun Shen2,3, Lin Su1, Yifei Hou1, Mingxi Liu1, Xiaoning Jiao1, Xiao Chen1, Shiguo Zhu1, Yechen Lu4, Chao Yao1, Lixin Wang1, Chenyuan Gong1, Zhenzhen Ma4, Chunpu Zou1, Jianguang Xu4,5. 1. School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2. Department of Orthopedics, Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai, China. 3. Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 4. School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 5. Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China.
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 IL-17-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 IL-17A, interferon-γ (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 nuclear transcription factor κB (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 IL-17A in CD4+ T lymphocytes. The titer of IL-17A 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. CONCLUSION: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4+ T lymphocyte-β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.
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 IL-17-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 IL-17A, interferon-γ (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 nuclear transcription factor κB (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 IL-17A in CD4+ T lymphocytes. The titer of IL-17A 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. CONCLUSION: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4+ T lymphocyte-β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.
Authors: José María G Ruiz de Morales; Lluís Puig; Esteban Daudén; Juan D Cañete; José Luis Pablos; Antonio Olveira Martín; Carlos González Juanatey; Alfredo Adán; Xavier Montalbán; Natalia Borruel; Guillermo Ortí; Esther Holgado-Martín; Carolina García-Vidal; Cynthia Vizcaya-Morales; Víctor Martín-Vázquez; Miguel Ángel González-Gay Journal: Autoimmun Rev Date: 2019-11-15 Impact factor: 9.754
Authors: Patrick A Hughes; Andrea M Harrington; Joel Castro; Tobias Liebregts; Birgit Adam; Dallas J Grasby; Nicole J Isaacs; Lochana Maldeniya; Chris M Martin; Jenny Persson; Jane M Andrews; Gerald Holtmann; L Ashley Blackshaw; Stuart M Brierley Journal: Gut Date: 2012-07-05 Impact factor: 23.059