• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2
【24h】

Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2

机译：缺乏趋化因子受体CCR2的小鼠的神经性疼痛反应受损

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mice lacking the chemokine receptor chemotactic cytokine receptor 2 (CCR2) have a marked attenuation of monocyte recruitment in response to various inflammatory stimuli and a reduction of inflammatory lesions in models of demyelinating disease. In the present study, we compared nociceptive responses in inflammatory and neuropathic models of pain in CCR2 knockout and wildtype mice. In acute pain tests, responses were equivalent in CCR2 knockout and wild-type mice. In models of inflammatory pain, CCR2 knockout mice showed a 70% reduction in phase 2 of the intraplantar formalin-evoked pain response but only a modest (20-30%) and nonsignificant reduction of mechanical allodynia after intraplantar Freund's adjuvant (CFA). In a model of neuropathic pain, the development of mechanical allodynia was totally abrogated in CCR2 knockout mice. CFA administration induced marked up-regulation of CCR2 mRNA in the skin and a moderate increase in the sciatic nerve and dorsal root ganglia (DRG). In response to nerve ligation, persistent and marked up-regulation of CCR2 mRNA was evident in the nerve and DRG. Disruption of Schwann cells in response to nerve lesion resulted in infiltration of CCR2-positive monocytes/macrophages not only to the neuroma but also to the DRG. Chronic pain also resulted in the appearance of activated CCR2-positive microglia in the spinal cord. Collectively, these data suggest that the recruitment and activation of macrophages and microglia peripherally and in neural tissue may contribute to both inflammatory and neuropathic pain states. Accordingly, blockade of the CCR2 receptor may provide a novel therapeutic modality for the treatment of chronic pain. [References: 32]
机译：在脱髓鞘疾病模型中，缺乏趋化因子受体趋化性细胞因子受体2（CCR2）的小鼠对单核细胞募集有明显的减弱，以响应各种炎症刺激，并减轻了炎症损伤。在本研究中，我们比较了CCR2基因敲除和野生型小鼠疼痛的炎症和神经病理模型的伤害感受反应。在急性疼痛试验中，CCR2基因敲除小鼠和野生型小鼠的反应相当。在炎性疼痛模型中，CCR2基因敲除小鼠的足底福尔马林引起的疼痛反应的第2阶段减少了70％，但仅在足底内使用弗氏佐剂（CFA）后机械性异常性疼痛减轻了适度（20-30％），并且无明显减少。在神经性疼痛模型中，CCR2基因敲除小鼠完全消除了机械性异常性疼痛的发生。给予CFA会引起皮肤中CCR2 mRNA的明显上调，并且坐骨神经和背根神经节（DRG）会适度增加。响应神经结扎，在神经和DRG中CCR2 mRNA持续且明显上调。雪旺细胞对神经损伤的反应破坏不仅导致CCR2阳性单核细胞/巨噬细胞浸润到神经瘤，还浸润到DRG。慢性疼痛还导致脊髓中出现活化的CCR2阳性小胶质细胞。总体而言，这些数据表明，巨噬细胞和小胶质细胞在周围和神经组织中的募集和激活可能导致炎性和神经性疼痛状态。因此，CCR2受体的阻断可以为慢性疼痛的治疗提供新的治疗方式。 [参考：32]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号