背根神经节
伤害
微量注射
神经病理性疼痛
医学
坐骨神经
神经损伤
脊髓
下调和上调
神经科学
麻醉
生物
内科学
受体
基因
生物化学
作者
Luyao Zhang,Xiang Li,Xiaozhou Feng,Tolga Berkman,Ruining Ma,Shouying Du,Shaogen Wu,Chen Huang,Akwasi Amponsah,Alex Bekker,Yuan‐Xiang Tao
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2022-05-04
卷期号:164 (1): 119-131
被引量:6
标识
DOI:10.1097/j.pain.0000000000002673
摘要
Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown. We report here that peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve or unilateral fourth lumbar spinal nerve ligation led to the time-dependent increases in the levels of Elf1 mRNA and ELF1 protein in injured DRG, but not in the spinal cord. Preventing this increase through DRG microinjection of adeno-associated virus 5 expressing Elf1 shRNA attenuated the CCI-induced upregulation of matrix metallopeptidase 9 (MMP9) in injured DRG and induction and maintenance of nociceptive hypersensitivities, without changing locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking this increase through DRG microinjection of AAV5 expressing full-length Elf1 upregulated DRG MMP9 and produced enhanced responses to mechanical, heat, and cold stimuli in naive mice. Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons after CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. E74-like factor 1 may be a new target for management of neuropathic pain.
科研通智能强力驱动
Strongly Powered by AbleSci AI