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Study on the peripheral mechanism of muscular mechanical hyperalgesia using the delayed onset muscle soreness as a model

以迟发性肌肉酸痛为模型研究肌肉机械性痛觉过敏的外周机制

基本信息

批准号：
18390069
负责人：
MIZUMURA Kazue
金额：
$ 9.6万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390069/
关键词：
muscular mechanical hyperalgesia bradykinin COX2 nerve growth factor (NGF)delayed onset muscle soreness ATP lengthening contraction muscle thin-fiber receptors COX1 筋性疼痛機械痛覚過敏プロスタグランジン

项目摘要

To clarify the mechanism for the muscular mechanical hyperalgesia, following three points were examined using a rat model of delayed onset muscle soreness that was induced by loading lengthening contraction (LC). 1. Change of sensitizing substances in the muscle that is released by compression of the muscle or during contraction, and sensitization of muscle C-fiber receptors by these substances. 2. Change in ion channels and reception expressed in muscle C-fiber sensory receptor neurons. 3. Change in physical (mechanical) environment of muscle sensory receptors in edematous muscle after LC. We found: 1. ATP was released by compression of the muscle, but its amount was not different between the muscles before and 2 days after LC. ATP 0.1-100 μM rather suppressed the response of muscle C-fiber receptors to the mechanical stimulation. Administration of bradykinin receptor antagonists, Cox inhibitors and anti-NGF (nerve growth factor) antibody at different time points around LC revealed that bradykinin through B2 receptors and Cox-2 were involved in triggering the process to mechanical hyperalgesia, and that NGF was involved in maintenance of mechanical hyperalgesia. Corresponding to these observations expression of Cox-2 mRNA and protein increased during 0 12 hr after LC whereas NGF mRNA increased during 12 hr 2 days after LC. NGF facilitated the mechanical response of muscle thin-fiber receptors recorded in vitro, supporting the role of NGF in mechanical hyperalgesia after LC. 2. Suppression subtractive hybridization analysis of mRNA in DRGs after exercise revealed upregulation of RNAs of 65 substances. RTPCR of two of them, pain-related annexin A2 and calbindin 1, showed significant increase 2 days after LC. 3. The muscle 2 days after LC was by about 5% heavier, suggesting existence of edema after I.C. Immunohistochemistry of aquaporin 1 and 4 in muscle showed no consistent change after LC.

为了阐明肌肉机械痛觉过敏的机制，使用由负荷延长收缩（LC）诱导的延迟性肌肉酸痛大鼠模型检查了以下三点。 1.肌肉受压或收缩时释放的致敏物质发生变化，这些物质对肌肉C纤维受体的致敏作用。 2.肌肉C纤维感觉受体神经元表达的离子通道和接收的变化。 3. LC后水肿肌中肌肉感觉受体物理（机械）环境的变化。我们发现： 1. ATP 通过肌肉受压而释放，但 LC 前和 2 天后肌肉之间其量没有差异。 ATP 0.1-100 μM 相当抑制肌肉 C 纤维受体对机械刺激的反应。在 LC 前后的不同时间点给予缓激肽受体拮抗剂、Cox 抑制剂和抗 NGF（神经生长因子）抗体表明，缓激肽通过 B2 受体和 Cox-2 参与触发机械痛觉过敏过程，而 NGF 参与机械痛觉过敏的维持。与这些观察相对应，Cox-2 mRNA和蛋白质的表达在LC后0-12小时内增加，而NGF mRNA在LC后12小时2天内增加。 NGF 促进体外记录的肌肉细纤维受体的机械反应，支持 NGF 在 LC 后机械痛觉过敏中的作用。 2.运动后DRGs中mRNA的抑制消减杂交分析显示65种物质的RNA上调。其中两个（与疼痛相关的膜联蛋白 A2 和钙结合蛋白 1）的 RTPCR 在 LC 后 2 天显示显着增加。 3. LC后2天肌肉重约5%，提示I.C后存在水肿。 LC 后肌肉中水通道蛋白 1 和 4 的免疫组织化学未显示一致的变化。