The contribution of spinal dorsal horn astrocytes in neuropathic pain at the early stage of EAE

The contribution of spinal dorsal horn astrocytes in neuropathic pain at the early stage of EAE
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DOI:
10.1016/j.nbd.2022.105914
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发表时间:
2022-11-03
影响因子:
6.1
通讯作者:
Yang, Fei
Yang, Fei
中科院分区:
医学1区
文献类型:
--
作者:
Ding, Yumeng;Hu, Liye;Yang, Fei

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反应性星形胶质细胞在多发性硬化中起着复杂的作用,星形胶质细胞的反应性是疼痛发病机制中的重要因素。探讨多发性硬化(MS)早期疼痛的发生发展机制,对该病的早期干预具有重要意义。本研究旨在探讨星形胶质细胞在实验性自身免疫性脑脊髓炎(EAE)模型不同阶段的反应性,以及星形胶质细胞在EAE早期疼痛中的作用。在这项研究中,我们证明了脊髓背角星形胶质细胞在EAE小鼠的临床前阶段被激活,并且脊髓星形胶质细胞反应性的抑制有效地减轻了EAE小鼠的疼痛症状。另一方面,脊髓小胶质细胞不直接参与EAE早期疼痛。此外,离子通道LRRC8A通过调节STAT3通路介导脊髓背角星形胶质细胞的反应性,因此在EAE的早期疼痛中发挥作用。
Reactive astrocytes play a complex role in multiple sclerosis, and the astrocytes reactivity is an important factor in the pathogenesis of pain. It is of great significance to explore the genesis and development mechanism of pain in the early stage of multiple sclerosis (MS) for early intervention of the disease. This study aims to explore astrocyte reactivity at different stages of the experimental autoimmune encephalomyelitis (EAE) model, a mouse model of MS, and the role of astrocytes in the pain in the early stage of the EAE. In this study, we demonstrated that spinal dorsal horn astrocytes were activated in the pre-clinical stage of EAE mice, and the inhibition of spinal cord astrocyte reactivity effectively alleviates pain symptoms in EAE mice. On the other hand, spinal cord microglia were not directly participated in the early EAE pain. Moreover, the ion channel LRRC8A mediated the reactivity of spinal dorsal horn astrocytes by regulating the STAT3 pathway, therefore playing a role in the early pain of EAE.