Journal of Inflammation Research
·
2024
·
IF 4.2
Kaifang Yao,Zhihan Chen,Yanwei Li,Baomin Dou,Zhifang Xu,Yajing Ma,Simin Du,Jiangshan Wang,Jiangjiang Fu,Qi Liu,Zezhi Fan,Yangyang Liu,Xiaowei Lin,Yuan Xu,Yuxin Fang,Shenjun Wang,Yi Guo
Purpose Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods We injected complete Freund’s adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1−/− mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1−/− ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.
研究领域:
疼痛研究
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神经科学
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免疫学
·
中医
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 5.9
Jiangjiang Fu,Gangchen Cheng,Zhongxi Lyu,Zezhi Fan,Feiyang Li,Zhifang Xu,Bo Chen,Yongming Guo,Yuhan Liu,Hui Zhang,Yuan Xu,Yi Guo
Introduction: The acupuncture acupoint is the critical initial site for the therapeutic efficacy of electroacupuncture (EA). Previous studies have confirmed that the NF-κB pathway within the acupoint region mediates the therapeutic effects of acupuncture. Therefore, this study focuses on an in-depth investigation of the MD2/TLR4/NF-κB axis. Methods: The mouse model of adjuvant-induced arthritis (AIA) was established via intraplantar injection of Complete Freund’s Adjuvant (CFA). EA intervention was applied bilaterally to the Zusanli (ST36) acupoints, and behavioral, molecular, and immunological approaches were integrated to investigate the role of MD2 in EA-mediated analgesia. Results: EA increased paw thermal withdrawal thresholds (PTWTs) in AIA mice (P < 0.05), accompanied by higher levels of MD2, TLR4, p65, and the phosphorylated form of p65 (p-p65) at the acupoint. Co-immunoprecipitation (Co-IP) confirmed binding between MD2 and TLR4 in ST36 acupoint, while immunofluorescence (IF) revealed co-localization of TLR4 with fibroblasts and mast cells in ST36, suggesting these immune cells are critical targets for signal activation. Lentivirus-mediated knockdown of MD2 in the acupoint partially reversed EA’s analgesic effects and suppressed downstream TLR4/NF-κB pathway activation, whereas MD2 overexpression elicited a partial analgesic effect and promoted pathway activation. Together with spinal cord proteomics data, these findings indicate that modulating MD2 in the acupoint can regulate spinal cord-related signaling pathways. Mechanistically, EA dynamically regulates the equilibrium of the Grem1/BMP4/COX2 axis in the spinal dorsal horn via activation of the MD2/TLR4/NF-κB pathway cascade, achieving systemic analgesia. Conclusion: This study provides molecular evidence supporting the "acupoint priming" theory in acupuncture and highlights MD2 as a potential therapeutic target for pain management.
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PubMed
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Xiujuan Li,Zehao Chen,Songgen Chen,Han Wang,Lin Fu,Ban Feng,Hui Chen,Lize Xiong
Pain represents a significant public health challenge with substantial clinical and economic burdens. While pharmacotherapy remains a mainstay of pain management, its utility is limited by adverse side effects and the potential for dependency. Acupuncture has shown great potential in pain management through its ability to induce analgesic effects via acupoint stimulation. However, its poor specificity and ill-defined stimulation parameters compromise therapeutic specificity and reproducibility. Herein, we developed a biomaterial-based acupoint activation strategy for pain management. Adhesive polydopamine-coated hydrogel microspheres were fabricated using microfluidic techniques for accurate attachment and activation of acupoints. Adhesive hydrogel microspheres loaded with adenosine can slowly release exogenous adenosine at the ST36 acupoint to simulate the analgesic effect of acupuncture. In vitro and in vivo studies demonstrated that single-dose administration of adhesive microspheres can effectively target acupoints, elevate mechanical pain thresholds, and provide systemic anti-inflammatory effects for up to 7 days. Overall, the proposed adhesive hydrogel microsphere system offers a new perspective on acupuncture practice and pain management.
研究领域:
生物医学工程
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疼痛医学
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生物材料
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药物递送系统
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针灸研究
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高影响因子
Journal of Traditional Chinese Medicine
·
2026
·Vol. 46
·期 3
·594
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IF 2.6
Feng HAO,Jiajia SANG,Chuanyu PENG,Jun HU,Zijian WU,Ling HU,Yihuang GU
OBJECTIVE: To investigate the effects of moxibustion at Zusanli (ST36) on ferroptosis-related proteins in synovial inflammation of rats with rheumatoid arthritis (RA) and verify the mechanism by cell experiments. METHODS: A RA rat model was established using a "disease-syndrome integration" modeling method. The rats were randomly divided into a blank control group (Control group) and a model replication group. Rats with successfully replicated RA models were further divided into a model control group (RA group) and a moxibustion treatment group (RA + Mox group). After intervention, the rats' ankle swelling degree and small animal ultrasound examination were conducted and synovial tissue was examined for pathology, lipid reactive oxygen species (ROS) detection, ferrous ion Fe 2+ double staining, and immunohistochemistry analysis. Serum from three groups of rats were extracted and used for cellular assays, cell counting kit-8 and Western blot validation. RESULTS: (a) Compared to Control group rats, RA rats showed significantly increased footpad swelling ( P < 0.01) and joint inflammation levels ( P < 0.001); compared to RA group, the RA + Mox rats showed significantly decreased footpad swelling ( P < 0.05) and joint inflammation levels ( P < 0.01). (b) There was no difference in lipid ROS levels in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but the lipid ROS levels in the synovial tissue of RA + Mox rats were significantly increased ( P < 0.01). Compared to Control group rats, RA rats had significantly lower Fe 2+ levels ( P < 0.05); compared to RA rats, the Fe 2+ levels in RA+Mox rats were significantly increased ( P < 0.01). There was no significant difference in beclin 1(BECN1) expression in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but BECN1 expression in the synovial tissue of RA + Mox rats was significantly increased ( P < 0.01) compared to RA rats. Compared to Control group rats, RA rats had significantly higher Solute Carrier Family 7 Member 11 Gene (SLC7A11) levels in synovial tissue ( P < 0.05); compared to RA rats, the SLC7A11 levels in RA + Mox rats were significantly decreased ( P < 0.05). (c) In the lipopolysaccharides (10 ng/mL) model, 50% concentration of RA rats serum promoted human RA fibroblast-like synovial cell line (MH7A) proliferation (48 h) ( P < 0.05) and 50% concentration of RA + Mox rat serum inhibited MH7A proliferation (48, 72 h) ( P < 0.001). Both 25% and 50% concentrations of RA + Mox rat serum upregulated BECN1 and downregulated SLC7A11 expression in MH7A. CONCLUSION: Moxibustion at Zusanli (ST36) suggests a potential to relieve footpad swelling and synovial inflammation in RA rats, alleviate synovial tissue hyperplasia and thickening. It may induce lipid ROS accumulation in synovial tissue, upregulating Fe 2+ levels, upregulating BECN1 expression, and downregulating SLC7A11 expression in RA rats. Moreover, 50% concentration of rat serum after moxibustion inhibited the proliferation of synovial fibroblasts and regulated the expression of ferroptosis-related proteins.
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高影响因子
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