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

J Clin Invest. 2022 Jul 1;132(13):e153563. doi: 10.1172/JCI153563.


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.

Keywords: Cell Biology; Epigenetics; Neurological disorders; Neuroscience.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Humans
  • Neuralgia* / genetics
  • Neuralgia* / metabolism
  • Neuralgia* / pathology
  • Peripheral Nerve Injuries* / genetics
  • Peripheral Nerve Injuries* / metabolism
  • Peripheral Nerve Injuries* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism


  • CCL2 protein, human
  • Chemokine CCL2
  • RNA, Long Noncoding