神经病理性疼痛
痛觉过敏
星形胶质细胞
慢性疼痛
神经科学
医学
MECP2
中枢神经系统
伤害
心理学
内科学
生物
受体
表型
生物化学
基因
作者
Mengchan Ou,Yali Chen,Jin Liu,Donghang Zhang,Yaoxin Yang,Jiefei Shen,Changhong Miao,Shao‐Jun Tang,Xin Liu,Daniel K. Mulkey,Tao Zhu,Cheng Zhou
标识
DOI:10.1016/j.pneurobio.2023.102436
摘要
Astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain, but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.1) is the most important background K+ channel in astrocytes. However, how Kir4.1 is regulated and contributes to behavioral hyperalgesia in chronic pain is unknown. In this study, single-cell RNA sequencing analysis indicated that the expression levels of both Kir4.1 and Methyl-CpG-binding protein 2 (MeCP2) were decreased in spinal astrocytes after chronic constriction injury (CCI) in a mouse model. Conditional knockout of the Kir4.1 channel in spinal astrocytes led to hyperalgesia, and overexpression of the Kir4.1 channel in spinal cord relieved CCI-induced hyperalgesia. Expression of spinal Kir4.1 after CCI was regulated by MeCP2. Electrophysiological recording in spinal slices showed that knockdown of Kir4.1 significantly up-regulated the excitability of astrocytes and then functionally changed the firing patterns of neurons in dorsal spinal cord. Therefore, targeting spinal Kir4.1 may be a therapeutic approach for hyperalgesia in chronic neuropathic pain.
科研通智能强力驱动
Strongly Powered by AbleSci AI