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Papers of the Week

Papers: 2 Jul 2022 - 8 Jul 2022

Animal Studies, Pharmacology/Drug Development

2022 Jul 01

J Clin Invest



Editor's Pick

A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression.


Du S, Wu S, Feng X, Wang B, Xia S, Liang L, Zhang L, Govindarajalu G, Bunk A, Kadakia F, Mao Q, Guo X, Zhao H, Berkman T, Liu T, Li H, Stillman J, Bekker A, Davidson S, Tao Y-X
J Clin Invest. 2022 Jul 01; 132(13).
PMID: 35775484.


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.