基于5-HT/5-HT2A受体/PLC/TRPV1信号通路探讨银质针治疗肌筋膜疼痛综合征的机制研究
批准号:
82060811
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
王林
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
王林
中文摘要
肌筋膜疼痛综合征(MPS)是临床常见而难治性痛疾,发病机制仍不清晰。临床证实银质针导热治疗MPS具有较好的长期缓解疼痛疗效,但机制不明。研究表明5-HT作用于5-HT2A受体(5-HT2AR)后可通过PLC介导TRPV1脱敏;另TRPV1可被热效应激活,TRPV1持续激活后可脱敏而降低脊髓SP、CGRP等表达发挥镇痛效应。我们前期研究发现银质针导热可增加MPS大鼠脊髓5-HT和5-HT2AR的表达,据此推测银质针导热可能是通过5-HT/5-HT2AR/PLC/TRPV1信号通路发挥镇痛作用。因此本项目拟以MPS大鼠和原代培养的脊髓神经细胞为研究对象,采用行为学、电生理学、组织形态学和分子生物学等手段,探讨5-HT/5-HT2AR/PLC/TRPV1通路在MPS病理过程中的机制,明确银质针导热治疗MPS是否通过该通路发挥针刺与热效应双重镇痛效应,为临床采用银质针导热治疗MPS提供理论依据。
英文摘要
MPS myofascial pain syndrome (MPS) is a common and refractory pain disease in clinic. The pathogenesis of MPS is still unclear. Clinical studies have confirmed that silver needle heat conduction therapy for MPS has a prefect long-term pain relief effect, but the mechanism is unknown. Studies have shown that 5-HT acting on the 5-HT2A receptor can desensitize TRPV1 through PLC-mediated. In addition, TRPV1 can be activated by thermal effects. TRPV1 can be desensitized after sustain activation. The desensitization of TRPV1 can reduce the expression of SP and CGRP in spinal cord to exert an analgesic effect. Our previous research found that silver needle heat conduction can increase the expression of 5-HT and 5-HT2AR in the spinal cord of MPS rats. It is speculated that silver needle heat conduction may play analgesic effect through the 5-HT/ 5-HT2AR/PLC/TRPV1 signaling pathway. Therefore, our study intends to use MPS rats and primary cultured spinal nerve cells as the research object, applying behavioral, electrophysiology, histomorphology and molecular biology to explore the pathological mechanism of 5-HT/5-HT2AR/ PLC/TRPV1 pathway in MPS and whether the silver needle heat conduction therapy for MPS can exert the dual analgesic effect with combined acupuncture and heat action through this pathway, which might provide a theoretical basis on the clinical use of silver needle thermal conduction therapy for MPS.
本课题以肌筋膜疼痛综合征(MPS)大鼠为研究对象,深入探讨了银质针导热疗法的镇痛机制。通过体内和体外实验,课题组取得了以下重要成果:1.银质针导热疗法的疗效验证及银质针导热疗法双重镇痛机制的揭示:成功建立了MPS大鼠模型,并证实银质针导热疗法能够显著提高大鼠的热痛阈和机械痛阈,恢复异常肌电信号,修复肌组织病理形态。银质针导热疗法的针刺效应和热效应均可通过调节脊髓5-HT2A受体和TRPV1表达,减少SP表达,发挥镇痛作用。这一发现为优化临床治疗方案提供了理论支持。2.阐明脊髓星形胶质细胞通过5-HT2A/PKC/ GAT-1信号通路调节星形胶质细胞对GABA的重摄取,发挥对MPS的镇痛作用。通过体内和体外实验,课题组揭示了银质针导热疗法通过调节脊髓5-HT2A受体激活PKC,进而抑制GAT-1表达,增加GABA浓度,发挥镇痛作用。3.脊髓代谢组学分析:基于LC-MS/MS的非靶向代谢组学检测发现,银质针导热疗法可能通过调节2-氧代羧酸代谢、细胞色素P450代谢异生素、淀粉和蔗糖代谢等途径发挥镇痛作用。这一发现为从代谢层面理解银质针导热疗法的机制提供了新的视角。4.此外,还发现银质针导热疗法可影响脊髓5-HT3受体的表达,进一步丰富了其多靶点镇痛机制。5.探索了银质针导热疗法对大鼠肌肉硬度、筋膜纤维化的影响,证实MPS大鼠筋膜出现纤维化,局部硬度增加,银质针导热可改善MPS大鼠局部纤维化及硬度。本项目对银质针导热疗法的作用机制进行了较深入的探索,所得结论为临床治疗提供更全面的理论支持。
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