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Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41467-019-13839-2 Xiaobing Yu 1 , Hongju Liu 1, 2 , Katherine A Hamel 3 , Maelig G Morvan 4 , Stephen Yu 3 , Jacqueline Leff 1 , Zhonghui Guan 1 , Joao M Braz 3 , Allan I Basbaum 3
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41467-019-13839-2 Xiaobing Yu 1 , Hongju Liu 1, 2 , Katherine A Hamel 3 , Maelig G Morvan 4 , Stephen Yu 3 , Jacqueline Leff 1 , Zhonghui Guan 1 , Joao M Braz 3 , Allan I Basbaum 3
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Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.
中文翻译：
背根神经节巨噬细胞有助于神经性疼痛的发生和持续。
周围神经损伤后平行激活背角小胶质细胞是背根神经节（DRG）中受损感觉神经元周围巨噬细胞的显着扩展和增殖。在这里，我们证明了DRG巨噬细胞对表征神经性疼痛表型的机械性超敏反应的引发和维持的关键贡献，但不是神经损伤部位的巨噬细胞。与小胶质细胞对神经性疼痛的贡献有关的性二态性不同，DRG巨噬细胞的耗竭减少了雄性和雌性小鼠中神经损伤引起的机械性超敏反应和DRG巨噬细胞的扩增。但是，雌性小鼠中诱导的巨噬细胞较少，并且感觉神经元中的集落刺激因子1缺失，它可以防止神经损伤引起的小胶质细胞活化和增殖，仅能减少雄性小鼠的巨噬细胞扩增。最后，我们证明了轴突切除的感觉神经元和巨噬细胞之间的分子串扰，揭示了神经病性疼痛管理的潜在外周DRG目标。
更新日期：2020-01-14
中文翻译：
背根神经节巨噬细胞有助于神经性疼痛的发生和持续。
周围神经损伤后平行激活背角小胶质细胞是背根神经节（DRG）中受损感觉神经元周围巨噬细胞的显着扩展和增殖。在这里，我们证明了DRG巨噬细胞对表征神经性疼痛表型的机械性超敏反应的引发和维持的关键贡献，但不是神经损伤部位的巨噬细胞。与小胶质细胞对神经性疼痛的贡献有关的性二态性不同，DRG巨噬细胞的耗竭减少了雄性和雌性小鼠中神经损伤引起的机械性超敏反应和DRG巨噬细胞的扩增。但是，雌性小鼠中诱导的巨噬细胞较少，并且感觉神经元中的集落刺激因子1缺失，它可以防止神经损伤引起的小胶质细胞活化和增殖，仅能减少雄性小鼠的巨噬细胞扩增。最后，我们证明了轴突切除的感觉神经元和巨噬细胞之间的分子串扰，揭示了神经病性疼痛管理的潜在外周DRG目标。
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