Systemic and molecular analysis on the pathology of newly-developed myopathic chronic pain models

本研究采用我们研制的两种慢性疼痛动物模型（肌伤害性模型和固定模型）。这些模型的特点是：1)没有给出直接的神经损伤；2)形成双侧广泛性持久疼痛行为。本研究的目的是阐明这些模型的慢性疼痛机制。在这些模型的慢性疼痛期，后爪对侧痛觉过敏不受同侧坐骨神经阻滞的影响。这一结果暗示了中枢可塑性的含义。固定模型L4背角取模后早期的小胶质细胞和慢性疼痛期的星形胶质细胞被激活。当足跖痛觉倾向于减弱时，两种类型的脊髓胶质细胞的激活均减少。尾椎脊髓的小胶质细胞活化比L4的慢。该模型提示脊髓胶质细胞的作用。作为初步检查，采用pcr法检测脊髓和肌肉组织中IL-6和BDNF mRNA表达。在固定模型中，通过遥测记录自主神经参数（血压、心率），交感神经活动在固定模型中增强，但在持续疼痛行为中下降到正常水平以下。在慢性疼痛状态下，对冷暴露的自主神经反应高于正常状态。据报道，慢性疼痛患者（如CRPS i型）存在自主神经功能障碍，因此该模型可能是这些致病性疾病的部分解释。在肌-伤害性模型中，治疗到年轻时没有产生慢性疼痛行为。这表明任何触发慢性疼痛的因素都可能是不成熟的。二甲胺四环素注射和跑步机运动都倾向于减少疼痛行为，尽管需要重新检查。

In this study, two types of chronic pain animal models (myo-nociceptive model, cast-immobilization model) we had developed were used. The characteristics of these models are: 1) direct nerve injuries are not given; 2) bilateral wide-spread long-lasting pain behaviors are developed. The purpose of this study is to clarify the chronic pain mechanisms of these models.1. In the chronic pain phase of these models, the contralateral hyperalgesia in the hind-paw was not affected by the ipsilateral sciatic nerve block. This result suggests the implication of central plasticity.2. In the L4 dorsal horn of the cast-immobilization model, the microglias at the early phase after cast-removal and the astrocytes at the chronic pain phase had activated. When the paw hyperalgesia tend to attenuate, the activation of both types of spinal glial cells reduced. In the coccygeal cord, the microglial activation appeared in retard of that in the L4. The implication of spinal glial cells is suggested in this model. As the preliminary examination, IL-6 and BDNF mRNA expressions in spinal cord and muscles were determined by PCR.3. In the cast-immobilization model, the autonomic parameters (blood pressure, heart rate) were telemetrically recorded, The sympathetic activity was augmented during cast-immobilization period and then decreased below the normal level while persisting pain behavior continued. In the chronic pain condition, the autonomic reactivities to cold-exposure were higher than in normal. Autonomic dysfunction in the chronic pain patients (e.g. CRPS type-I) is reported, so this model may be a partial explanation for those pathogenic conditions.4. In the myo-nociceptive model, the treatment to young-age was not produced chronic pain behaviors. It is suggested any factors as a trigger to chronic pain may be immature.5. Both of the minocycline injection and the treadmill exercise tended to decrease pain behaviors, though reexamination should be required.