CNS myeloid cells critically regulate heat hyperalgesia
CNS myeloid cells critically regulate heat hyperalgesia
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DOI：
10.1172/jci95305
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发表时间：
2018-07-02
影响因子：
15.9
通讯作者：
Heppner, Frank L.
中科院分区：
文献类型：
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作者：
Kalin, Stefanie;Miller, Kelly R.;Heppner, Frank L.
非神经元小胶质细胞的激活被认为在神经性疼痛的脊髓加工中起因果作用。为了专门研究小胶质细胞在神经性疼痛模型中的介导作用，并克服以往探索小胶质细胞在神经损伤中的功能方法的局限性，我们通过向cd11b - hsvtk转基因雄性小鼠脑室内注入更昔洛韦，选择性地消融了小胶质细胞，随后外周髓细胞快速、完整、持续（23周）地再生中枢神经系统。在接受坐骨神经损伤的小鼠中，我们观察到对机械刺激的正常反应，但在损伤神经的同侧没有热超敏反应。此外，我们发现再生小鼠脊髓背角中降钙素基因相关肽（CGRP）的神经元表达减少，CGRP是热反应必需的神经元标志物。这些发现确定了热和机械超敏反应的不同机制，并强调了中枢神经系统髓样细胞在促进有害热方面的重要贡献。
Activation of non-neuronal microglia is thought to play a causal role in spinal processing of neuropathic pain. To specifically investigate microglia-mediated effects in a model of neuropathic pain and overcome the methodological limitations of previous approaches exploring microglia function upon nerve injury, we selectively ablated resident microglia by intracerebroventricular ganciclovir infusion into male CD11b-HSVTK-transgenic mice, which was followed by a rapid, complete, and persistent (23 weeks) repopulation of the CNS by peripheral myeloid cells. In repopulated mice that underwent sciatic nerve injury, we observed a normal response to mechanical stimuli, but an absence of thermal hypersensitivity ipsilateral to the injured nerve. Furthermore, we found that neuronal expression of calcitonin gene-related peptide (CGRP), which is a marker of neurons essential for heat responses, was diminished in the dorsal horn of the spinal cord in repopulated mice. These findings identify distinct mechanisms for heat and mechanical hypersensitivity and highlight a crucial contribution of CNS myeloid cells in the facilitation of noxious heat.