Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury.
Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury.
复制标题
周围神经损伤后的疼痛超敏反应需要由常驻小胶质细胞增殖引起的脊髓小胶质细胞增生
DOI：
10.1016/j.celrep.2016.06.018
复制
发表时间：
2016-07-19
期刊：
影响因子：
8.8
通讯作者：
Wu LJ
中科院分区：
文献类型：
--
作者：
Gu N;Peng J;Murugan M;Wang X;Eyo UB;Sun D;Ren Y;DiCicco-Bloom E;Young W;Dong H;Wu LJ
周围神经损伤引起神经性疼痛，并伴有脊髓背角明显的小胶质细胞增生。然而，浸润的单核细胞是否有助于损伤诱导的小胶质细胞群的扩张仍然存在争议。在这里，我们使用两种遗传小鼠模型（CCR2RFP/+:CX3CR1GFP/+和CX3CR1creER/+:R26tdTomato/+小鼠）以及小胶质细胞和巨噬细胞的特异性染色，发现脊髓小胶质细胞增生主要是由驻留小胶质细胞的局部增殖引起的，而不是由浸润的单核细胞引起的。snt诱导的小胶质细胞增殖的药理抑制与神经性疼痛超敏反应的减轻相关。由于CX3CR1−/−和P2Y12−/−小鼠显示脊髓小胶质细胞增殖减少和神经性疼痛，小胶质细胞增殖部分受嘌呤能和fractalkine信号控制。这些结果表明，局部小胶质细胞增殖是脊髓小胶质增生的唯一来源，它代表了神经性疼痛管理的潜在治疗靶点。
Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT), using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice) as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.