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Papers of the Week


Papers: 30 Apr 2022 - 6 May 2022


2022 May 04


Pain

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E74-like factor 1 contributes to nerve trauma-induced nociceptive hypersensitivity via transcriptionally activating matrix metalloprotein-9 in dorsal root ganglion neurons.

Authors

Abstract

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 (ELF1in 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 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 naïve mice. Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons following CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. ELF1 may be a new target for management of neuropathic pain.