Manipulation therapy alleviates neuropathic pain via the SOCS1 m6A epigenetic loop
Manipulation therapy alleviates neuropathic pain via the SOCS1 m6A epigenetic loop
Wu Liping(School of Acupuncture-Moxibustion and Tuina, Chengdu University of Chinese Medicine, Chengdu, Sichuan Province, China); Wang Xiang(Department of Medicine, Saines College of New Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Yang Peng(Department of Tuina, Fangchenggang Hospital, Guangxi University of Chinese Medicine, Fangchenggang, Guangxi Zhuang Autonomous Region, China); Wang Xiongjiang(The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Zheng Yujiao(The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Tang Yeni(The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Zheng Haoxin(The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Ning Peng(The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China); Tang Hongliang(Department of Tuina, Fangchenggang Hospital, Guangxi University of Chinese Medicine, Fangchenggang, Guangxi Zhuang Autonomous Region, China)
39권 2호, 191~206쪽
초록
Background: Manipulation therapy (MT) relieves pain in nervous system disorders by reducing inflammation. Although evidence suggests MT is beneficial for neuropathic pain (NP), its molecular mechanisms remain unclear. This study investigated whether MT could reverse NP-related epigenetic changes and elucidated the potential mechanisms of NP. Methods: An NP model was established via spinal nerve ligation (SNL), and MT was administered at acupoints Jumping Round (GB30), Yang Mound Spring (GB34), and Suspended Bell (GB39) for 14 days. Mechanical and thermal pain in rats were evaluated using the mechanical paw withdrawal threshold and thermal paw withdrawal latency tests. Inflammatory cytokine levels in spinal cord neurons were quantified using enzyme-linked immunosorbent assay. Total N6-methyladenosine (m6A) levels were assessed by colorimetric analysis, while target genes were validated using methylated RNA immunoprecipitation succeeded by quantitative polymerase chain reaction, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction. Results: The outcomes indicated that MT significantly attenuated SNL-induced pain hypersensitivity. The therapeutic effects of MT were correlated with global m6A methylation in spinal cord neurons. Moreover, MT affected the toll-like receptor 4 (TLR4) signaling pathway’s expression by modulating suppressor of cytokine signaling 1 protein (SOCS1) mRNA m6A methylation levels, consequently reducing the secretion of neuroinflammatory cytokines interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), thereby alleviating NP. Conclusions: This study provides evidence that MT effectively ameliorates NP by modulating inflammation and RNA m6A methylation in the spinal cord via the SOCS1/TLR4 pathway.
Abstract
Background: Manipulation therapy (MT) relieves pain in nervous system disorders by reducing inflammation. Although evidence suggests MT is beneficial for neuropathic pain (NP), its molecular mechanisms remain unclear. This study investigated whether MT could reverse NP-related epigenetic changes and elucidated the potential mechanisms of NP. Methods: An NP model was established via spinal nerve ligation (SNL), and MT was administered at acupoints Jumping Round (GB30), Yang Mound Spring (GB34), and Suspended Bell (GB39) for 14 days. Mechanical and thermal pain in rats were evaluated using the mechanical paw withdrawal threshold and thermal paw withdrawal latency tests. Inflammatory cytokine levels in spinal cord neurons were quantified using enzyme-linked immunosorbent assay. Total N6-methyladenosine (m6A) levels were assessed by colorimetric analysis, while target genes were validated using methylated RNA immunoprecipitation succeeded by quantitative polymerase chain reaction, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction. Results: The outcomes indicated that MT significantly attenuated SNL-induced pain hypersensitivity. The therapeutic effects of MT were correlated with global m6A methylation in spinal cord neurons. Moreover, MT affected the toll-like receptor 4 (TLR4) signaling pathway’s expression by modulating suppressor of cytokine signaling 1 protein (SOCS1) mRNA m6A methylation levels, consequently reducing the secretion of neuroinflammatory cytokines interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), thereby alleviating NP. Conclusions: This study provides evidence that MT effectively ameliorates NP by modulating inflammation and RNA m6A methylation in the spinal cord via the SOCS1/TLR4 pathway.
- 발행기관:
- 대한통증학회
- 분류:
- 통증학