脊髓背角星形胶质细胞在实验性自身免疫性脑脊髓炎早期神经性疼痛中的作用。
The contribution of spinal dorsal horn astrocytes in neuropathic pain at the early stage of EAE.
作者信息
Ding Yumeng, Hu Liye, Wang Xiaotong, Sun Qingyu, Hu Tingting, Liu Jing, Shen Danmin, Zhang Yurui, Chen Wen, Wei Chao, Liu Meng, Liu Dianxin, Wang Peipei, Zhang Chenguang, Zhang Jiannan, Li Qian, Yang Fei
机构信息
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
出版信息
Neurobiol Dis. 2022 Dec;175:105914. doi: 10.1016/j.nbd.2022.105914. Epub 2022 Nov 1.
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.
反应性星形胶质细胞在多发性硬化中发挥着复杂的作用，且星形胶质细胞的反应性是疼痛发病机制中的一个重要因素。探索多发性硬化（MS）早期疼痛的发生发展机制对于该疾病的早期干预具有重要意义。本研究旨在探讨实验性自身免疫性脑脊髓炎（EAE）模型（一种MS小鼠模型）不同阶段的星形胶质细胞反应性，以及星形胶质细胞在EAE早期疼痛中的作用。在本研究中，我们证明EAE小鼠临床前期脊髓背角星形胶质细胞被激活，抑制脊髓星形胶质细胞反应性可有效减轻EAE小鼠的疼痛症状。另一方面，脊髓小胶质细胞未直接参与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，从而在EAE早期疼痛中发挥作用。
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