Temporal Kinetics of Microgliosis in the Spinal Dorsal Horn after Peripheral Nerve Injury in Rodents
Temporal Kinetics of Microgliosis in the Spinal Dorsal Horn after Peripheral Nerve Injury in Rodents
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DOI：
10.1248/bpb.b18-00278
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发表时间：
2018-07-01
影响因子：
2
通讯作者：
Tsuda, Makoto
中科院分区：
文献类型：
--
作者：
Kohno, Keita;Kitano, Junko;Tsuda, Makoto
神经性疼痛是神经损伤后的一种高度衰弱性慢性疼痛，是病理改变的神经系统功能异常的反映。以往的研究表明，脊髓背角（SDH）中激活的小胶质细胞是神经病理性疼痛的关键细胞中介。小胶质细胞增生是由周围神经损伤（PNI）建立的神经病理性疼痛模型中SDH中发生的显著细胞改变之一，但SDH小胶质细胞增生的详细表征尚未实现。在本研究中，我们用细胞周期S期的标记物乙炔脱氧尿苷（EdU）对增殖细胞进行了短脉冲标记，发现在PNI后32 h很少观察到SDH中的EdU（+）小胶质细胞，但在PNI后40 h迅速增加到峰值水平。许多EdU（+）小胶质细胞持续了接下来的20小时（PNI后60小时），并在第7天降低至基线。这些结果表明，PNI后快速诱导SDH小胶质细胞增殖爆发的时间窗很窄，这些时间限制的小胶质细胞增殖动力学可能有助于识别引起SDH中小胶质细胞活化的分子，这对于理解和管理神经性疼痛至关重要。
Neuropathic pain, a highly debilitating chronic pain following nerve damage, is a reflection of the aberrant functioning of a pathologically altered nervous system. Previous studies have implicated activated microglia in the spinal dorsal horn (SDH) as key cellular intermediaries in neuropathic pain. Microgliosis is among the dramatic cellular alterations that occur in the SDH in models of neuropathic pain established by peripheral nerve injury (PNI), but detailed characterization of SDH microgliosis has yet to be realized. In the present study, we performed a short-pulse labeling of proliferating cells with ethynyldeoxyuridine (EdU), a marker of the cell cycle S-phase, and found that EdU(+) microglia in the SDH were rarely observed 32 h after PNI, but rapidly increased to the peak level at 40 h post-PNI. Numerous EdU(+) microglia persisted for the next 20h (60h post-PNI) and decreased to the baseline on day 7. These results demonstrate a narrow time window for rapidly inducing a proliferation burst of SDH microglia after PNI, and these temporally restricted kinetics of microglial proliferation may help identify the molecule that causes microglial activation in the SDH, which is crucial for understanding and managing neuropathic pain.