Fn14 Participates in Neuropathic Pain Through NF-κB Pathway in Primary Sensory Neurons

Li Na Huang, Yun Zou, Shao Gen Wu, Hong Hong Zhang, Qing Xiang Mao, Jin Bao Li, Yuan Xiang Tao

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities. Conversely, mimicking this increase produced the increases in the levels of phosphorylated extracellular signal-regulated kinase ½ and glial fibrillary acidic protein in ipsilateral dorsal horn and the enhanced responses to mechanical, thermal, and cold stimuli in the absence of SNL. Mechanistically, the increased Fn14 activated the NF-κB pathway through promoting the translocation of p65 into the nucleus of the injured DRG neurons. Our findings suggest that Fn14 may be a potential target for the therapeutic treatment of peripheral neuropathic pain.

Original languageEnglish (US)
Pages (from-to)7085-7096
Number of pages12
JournalMolecular Neurobiology
Volume56
Issue number10
DOIs
StatePublished - Oct 1 2019

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Keywords

  • Fn14
  • NF-κB pathway
  • Neuropathic pain
  • Primary sensory neurons

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