AUTHOR=Chen Wei , Zhang Xiao-Ning , Su Yang-Shuai , Wang Xiao-Yu , Li Heng-Cong , Liu Yi-Han , Wan Hong-Ye , Qu Zheng-Yang , Jing Xiang-Hong , He Wei 

TITLE=Electroacupuncture activated local sympathetic noradrenergic signaling to relieve synovitis and referred pain behaviors in knee osteoarthritis rats

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 16 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1069965

DOI=10.3389/fnmol.2023.1069965

ISSN=1662-5099

ABSTRACT=Recent experimental efforts focus on the local control of articular inflammation by neuronal stimulation to avoid the systemic side-effects of conventional pharmacological therapies. Electroacupuncture (EA) has been proved to be useful for inflammation suppressing and pain reduction in knee osteoarthritis (KOA) patients, yet its mechanism remains unclear. In the present study, the KOA model was established by intra-articular injection of sodium monoiodoacetate (MIA)（1 mg/ 50ul）into the knee cavity. EA was delivered at the ipsilateral ST36-GB34 acupoints. The result showed that EA intervention at the mid-term phase of the articular inflammation but not at the early phase alleviated the inflammatory pain behaviors and cartilage damage. Mid-term EA suppressed the levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 in the synovium on day 9 after MIA via elevating the level of sympathetic neurotransmitters Norepinephrine (NE) in the synovium but not systematic NE or systematic adrenaline. Selective blocking of the sympathetic function (6-OHDA) and β2-adrenergic receptor (ICI 118,551) prevented the anti-inflammatory effects of EA. EA-induced increment of the NE in the synovium inhibited CXCL1-CXCR2 dependent overexpression of IL-6 in the synovial macrophages in a β2-adrenergic receptor-mediated manner. These results revealed that EA activated sympathetic noradrenergic signaling to control local inflammation in KOA rats and helped to design novel therapeutic neurostimulation strategies for inflammatory diseases.