神经病理性疼痛
下调和上调
医学
神经科学
麻醉
生物
基因
遗传学
作者
Huimin Zhou,Hengjun Xu,Run-Hang Sun,Ming Zhang,Xiaotong Li,Ya-Xuan Zhao,Kehui Yang,Runa Wei,Qiaoqiao Liu,Siyuan Li,Zhouya Xue,Ling-Yun Hao,Jing Wang,Qihui Wang,Hongjun Wang,Fang Gao,Jun‐Li Cao,Zhiqiang Pan
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2023-08-25
卷期号:165 (1): 75-91
标识
DOI:10.1097/j.pain.0000000000002986
摘要
Abstract Nerve injury–induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6 . Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury–induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain–like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.
科研通智能强力驱动
Strongly Powered by AbleSci AI