1. A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression
- Author
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Du, Shibin, Wu, Shaogen, Feng, Xiaozhou, Wang, Bing, Xia, Shangzhou, Liang, Lingli, Zhang, Li, Govindarajalu, Gokulapriya, Bunk, Alexander, Kadakia, Feni, Mao, Qingxiang, Guo, Xinying, Zhao, Hui, Berkman, Tolga, Liu, Tong, Li, Hong, Stillman, Jordan, Bekker, Alex, Davidson, Steve, and Tao, Yuan-Xiang
- Subjects
Neuralgia -- Development and progression -- Genetic aspects ,RNA -- Physiological aspects -- Health aspects ,Soft tissue injuries -- Genetic aspects -- Complications and side effects ,Chemokines -- Genetic aspects -- Health aspects ,Health care industry - Abstract
Maladaptive changes of nerve injury-associated genes in dorsal root ganglia (DRGs) are critical for neuropathic pain genesis. Emerging evidence supports the role of long noncoding RNAs (lncRNAs) in regulating gene transcription. Here we identified a conserved lncRNA, named nerve injury-specific lncRNA (NIS-lncRNA) for its upregulation in injured DRGs exclusively in response to nerve injury. This upregulation was triggered by nerve injury-induced increase in DRG ELF1, a transcription factor that bound to the NIS-lncRNA promoter. Blocking this upregulation attenuated nerve injury-induced CCL2 increase in injured DRGs and nociceptive hypersensitivity during the development and maintenance periods of neuropathic pain. Mimicking NIS-lncRNA upregulation elevated CCL2 expression, increased CCL2-mediated excitability in DRG neurons, and produced neuropathic pain symptoms. Mechanistically, NIS-lncRNA recruited more binding of the RNA-interacting protein FUS to the Ccl2 promoter and augmented Ccl2 transcription in injured DRGs. Thus, NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathic pain management., Introduction Peripheral neuropathic pain caused by primary damage or injury to the peripheral nervous system is a complex and debilitating major health problem. It impacts the quality of life of [...]
- Published
- 2022
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