Papers of the Week

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of 4 opioid receptor ( , , , and the cannabinoid CB1 receptor ( ) genes in the DRG regulate nociception. In this study, we determined the role of REST in the control of their expression in the DRG induced by spared nerve injury (SNI) in both male and female mice. Transcriptomic analyses of male mouse DRGs showed that SNI upregulated expression of and downregulated mRNA levels of all 4 opioid receptor and genes, but was upregulated in female mice. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of and . Chromatin immunoprecipitation analyses indicated differing levels of REST at these promoters in male and female mice. Full-length conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of and in the DRG in both male and female mice. Our results suggest that nerve injury represses the transcription of and via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain.