“感觉-交感”耦联在肌筋膜触发点活化中的作用及中枢机制研究

With the changes of the working and modern life style, muscle pain is common and prevalent disease, and seriously influences human health. It has been well accepted that muscle pain is usually due to active myofascial trigger points which are caused by abnormal posture and improper use of muscle. Effectively control of activation of myofascial trigger points is scientific issue in treating muscle pain. It has been reported that sympathetic fibers sprout in formulating peripheral “sensory-sympathetic” coupling in pathological pain, and promoted the process and chronicity of pathological pain. Our series of studies further reported the abnormal “sensory-sympathetic” coupling exposed to the acute muscle pain, during which thalamus MD/VM nuclei induced descending inhibition and facilitation were decreased and increased, and activities of sympathetic nervous system were significantly enhanced. Accordingly, the applicant hypothesizes that imbalanced homeostasis of thalamic MD/VM nuclei might be the critical factors in enhancement of sympathetic activities and the development of muscle pain. Combing behavioral, electrophysiological, morphological immunochemical, and molecular biological methods, the present research will explore and reveal the roles of thalamus and warm-heating stimulation in modulation of central “sensory-sympathetic” coupling in activation and development of acute and chronic muscle pain. It has important theoretical significance and provides new policy in clinical medicine for the prevention of activation of myofascial trigger points and treatment of chronic muscle pain.

随着现代工作及生活方式的改变，肌肉痛已成为危害人类健康的常见、多发病。已知，“潜在”的肌筋膜触发点出现“活化”，可诱发持续时间长短不一的肌肉痛。如何有效抑制肌筋膜触发点“活化”已成为治疗肌肉痛的关键科学问题。有研究指出外周交感神经在病理性痛中出现异常芽生，形成“感觉-交感”结构耦联，加重并促进疼痛慢性化。课题组研究则发现，肌肉痛早期即出现中枢“感觉-交感”异常耦联现象，表现为丘脑MD/VM核团介导的痛觉易化作用增强，抑制作用减弱，及交感活动异常增强。据此，申请者推测丘脑功能稳态失衡，可通过“感觉-交感”中枢耦联，促进肌筋膜触发点“活化”及肌肉痛慢性化。本课题联合电生理、行为学、免疫组化及分子生物学方法，冀望通过明晰急、慢性肌肉痛状态下的丘脑及温热刺激对“感觉-交感”中枢耦联的调控作用及机制，为预防肌筋膜触发点“活化”及防治肌肉痛慢性化提供新策略。

随着现代工作及生活方式的改变，肌肉痛已成为危害人类健康的常见、多发病。现已证实“活化”的肌筋膜触发点可以诱发持续时间长短不一的肌肉痛，而外周交感神经在病理性痛中出现异常芽生，形成“感觉-交感”结构耦联，能进一步促进疼痛慢性化。然而，“活化”肌筋膜触发点-肌肉痛-“感觉-交感”耦联，三者之间的联系仍缺乏足够的科研证据支持。基于申请者课题组提出的丘脑是痛觉内源性调控“启动子”关键核心假说，申请者推测丘脑功能稳态失衡可通过“感觉-交感”中枢耦联，促进肌筋膜触发点“活化”及肌肉痛慢性化。在本研究中，申请者及课题组详细开展了肌筋膜触发点模型大鼠慢性肌肉痛状态下的交感神经活动变化及痛觉内源性调控作用的可塑性变化研究，并在完全弗氏佐剂诱发的炎性肌肉痛、帕金森病状态下的高渗盐诱发的持续性肌肉痛及福尔马林肌肉注射诱发的炎性肌肉痛中对痛觉内源性调控作用的可塑性变化，丘脑背内侧核（Mediodorsal nucleus，MD核）和丘脑腹内侧核（Ventromedial nucleus，VM核）的作用，及交感神经活动变化给予了详细研究。研究成果如下：（1）“活化”的肌筋膜触发点通过增强痛觉内源性易化作用及交感神经活动在肌肉痛慢性化过程中发挥重要作用，而上述易化作用的增强和交感神经活动增强均由丘脑MD核团活动所介导；（2）慢性肌肉痛状态下及病理性痛状态下，痛觉内源性调控作用出现可塑性变化，表现为丘脑MD核团介导的痛觉内源性易化作用增强，而VM核团介导的痛觉抑制作用显著减弱；（3）丘脑MD和VM核团内的P2X受体和多巴胺受体在痛觉内源性调控中的作用不同；MD核团P2X3受体参与下行易化，D3受体抑制下行易化，而VM核团P2X3，D2及D3受体均参与下行抑制作用；（4）肌肉给予43℃温热刺激能选择性激活丘脑VM核团功能，增强痛觉下行抑制作用，进而抑制肌肉痛发生，并阻断肌肉痛慢性化。本课题研究成果为“活化”的肌筋膜触发点及“感觉-交感”耦联在肌肉痛及其慢性化中的重要作用提供了科研资料，并初步揭示丘脑多巴胺能受体在急、慢性肌肉痛和帕金森病病理性痛中的痛觉内源性下行易化和抑制中的不同作用。同时，本课题为“非痛性”43℃温热刺激治疗肌肉痛提供了补充资料。