Department of Neuropathology and.
Department of Plastic Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
J Clin Invest. 2018 Jul 2;128(7):2774-2786. doi: 10.1172/JCI95305. Epub 2018 May 21.
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.
非神经元小胶质细胞的激活被认为在神经性疼痛的脊髓处理中起因果作用。为了在神经性疼痛模型中专门研究小胶质细胞介导的影响，并克服以前研究神经损伤时小胶质细胞功能的方法学限制，我们通过向雄性 CD11b-HSVTK 转基因小鼠脑室内给予更昔洛韦来选择性地耗竭驻留小胶质细胞，随后外周髓样细胞迅速、完全且持续（23 周）重新填充中枢神经系统。在经历坐骨神经损伤的再殖小鼠中，我们观察到对机械刺激的正常反应，但对损伤神经同侧的热敏感性缺失。此外，我们发现，降钙素基因相关肽（CGRP）的神经元表达减少，CGRP 是热反应所必需的神经元标志物，在再殖小鼠的脊髓背角中减少。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。
