肌肉痛及其慢性化中枢调控作用失衡及P2X受体机制研究

Due to abnormal posture and improper use of muscle, muscle pain is common and prevalent disease, which may seriously influence human health. Despite the theory of the peripheral “ATP energy crisis” widely accepted in the initiation and development of the myofascial trigger point and muscle pain, the functions of ATP and its receptor (P2X receptor) in development and chronicity of muscle pain within the central nervous system (CNS) remain unclear. Our previous series of studies showed that subtypes of P2X receptors were involved in thalamic MD/VM mediated endogenous descending modulation of pain, and expressions of different subtypes of P2X receptors were increased or decreased during different processes of muscle pain. Accordingly, the applicant proposes here that the enhanced or decreased expression of P2X receptor subunits in thalamic MD/VM nuclei may be one of the critical factors to provoke strengthening of descending facilitatory and weakening of descending inhibitory modulations, resulting in initiating the ‘potential’ myofascial trigger points to be active, and cause chronicity of muscle pain. Based on the simultaneous recording model: spinal dorsal horn nociceptive neuron-thalamic MD/VM nuclei-gastrocnemius electromyogram (EMG), combing behavioral, morphological immunochemical, and molecular biological methods, the present study will explore and reveal the roles of central P2X receptor in development and chronicity of muscle pain and its treatment by means of warm-needle stimulation. The current application has important theoretical significance in providing new evidence in exploration of mechanisms and clinical rehabilitation for muscle pain.

由于不正常的姿势以及肌肉使用不当，近年来肌肉痛已经成为危害人类健康的常见、多发病。已知“ATP能量危机”在外周“肌筋膜触发点”的形成和肌肉痛的发生中起重要作用，但中枢ATP及其P2X受体在肌肉痛及慢性化中的作用尚未被阐明。课题组前期实验表明：P2X受体参与丘脑MD/VM核团介导的痛觉内源性易化和抑制调控作用，并在肌肉痛不同阶段出现表达增强和减弱现象。据此，申请者推测丘脑MD/VM核团内P2X受体不同亚型的表达增强或减弱导致痛觉内源性下行易化作用持续增强和下行抑制作用减弱，可能是促使“肌筋膜触发点”活化和肌肉痛慢性化的重要因素之一。基于电生理同步记录（脊髓背角伤害感受性神经元-丘脑MD/VM核团-腓肠肌肌电），联合行为学，免疫组化及分子生物学等方法，本课题将阐明P2X受体在肌肉痛及其慢性化中枢调控作用失衡及温针治疗中的作用，为肌肉痛的机制探索和临床康复提供科研新证据。

近年来，由于不正常的姿势以及肌肉使用不当等原因造成的肌肉软组织痛已成为危害人类健康的常见、多发病，而上述疾病慢性化后临床更是缺乏行之有效的治疗手段，这为个人和社会造成严重的精神和经济负担。本研究采用行为学、电生理学、免疫组织化学等多研究手段，从外周和中枢，离体和在体等多层面上分别探讨了生理性痛及病理性肌肉痛（弗氏佐剂炎性肌肉痛，帕金森神经病理性肌肉痛，糖尿病神经病理性肌肉痛）状态下的丘脑背内侧核（MD核）和丘脑腹内侧核（VM）核团介导的痛觉内源性调控作用的可塑性变化，及“非痛性”43℃温热刺激对上述病理性痛的调控影响及P2X受体及其他相关受体中枢药理学机制。课题组依次开展系列相关研究工作，完成了基金项目中的实/试验。课题组的研究在肌肉痛“疼痛-康复”研究领域取得新的研究成果，创新性提出：（1）急、慢性肌肉痛状态下的痛觉内源性调控作用呈现可塑性变化。具体表现为：急性肌肉痛状态下的痛觉内源性易化和抑制调控作用无显著改变；而在慢性肌肉痛状态下，痛觉内源性易化作用增强，而抑制作用显著减弱；（2）慢性肌肉痛状态下的痛觉内源性特异双调控通路的核心启动子“丘脑MD核和VM核团”功能状态亦出现显著改变：MD核团活动显著增强，而VM核团活动明显减弱；（3）肌肉内43℃温热刺激显著抑制肌肉痛程度，并阻断肌肉痛慢性化；同时，上述治疗手段不仅改善痛觉异常情况，也显著改善相关运动症状；（4）丘脑MD核团P2X3受体参与内源性下行易化，而VM核团P2X3受体参与痛觉下行抑制作用。本课题研究及相关成果初步揭示了肌肉痛及其慢性化的相关表现，并为43C温热刺激治疗肌肉痛提供了科研证据和治疗新思路，也为揭示嘌呤能受体在痛觉下行易化和抑制中的不同作用提供了科研新证据。

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