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

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.