CoREST1 in primary sensory neurons regulates neuropathic pain in male mice.

Epigenetic regulation is implicated in the neurogenesis of neuropathic pain. The repressor element 1 (RE1) silencing transcription factor (REST) corepressor (CoREST) proteins function as corepressors in the REST complex and/or LSD1 epigenetic complex. In the current study, we aimed to find the expression profile of CoREST1 in the dorsal root ganglion (DRG) and investigate whether it plays a role in neuropathic pain. The evoked pain behaviors in mice were examined by the von Frey test and thermal test in a spinal nerve ligation (SNL)-induced neuropathic pain mice model. CoREST1 siRNA or virus was administered by DRG microinjection or intrathecal injection. The CoREST1 expression in DRGs was examined by immunofluorescence, quantitative PCR, Western blotting, and co-immunoprecipitation. CoREST1 was non-selectively expressed in large, medium, and small DRG neurons, and it exclusively colocalized with LSD1. In neuropathic pain models, peripheral nerve injury induced the upregulation of CoREST1 and increased binding of CoREST1 with LSD1 in injured DRGs in male mice. Furthermore, CoREST1 siRNA prevented the development of SNL-induced pain hypersensitivity as well as led to the reduction of established pain hypersensitivity during the maintenance period in SNL mice. Conversely, the overexpression of CoREST1 in DRGs by in vivo transfection of virus-induced pain hypersensitivity in naive mice. Our study demonstrated that CoREST1, along with LSD1, was expressed in primary sensory neurons specifically in response to nerve injury, and promoted nociceptive pain hypersensitivity in mice. Thus, CoREST1 might serve as a potential target for treating neuropathic pain. In summary, CoREST1, along with LSD1, expressed in primary sensory neurons, was specifically in responses to nerve injury and further promotes the nociceptive pain hypersensitivity in mice. Knockdown of CoREST1 by siRNA could serve as a potential analgesic strategy for neuropathic pain. [Display omitted] • CoREST1 was expressed in the nuclei of DRG neurons, and it colocalized with LSD1. • Peripheral nerve injury increased CoREST1 expression and the binding of CoREST1 with LSD1 in injured DRGs in male mice. • Knockdown of CoREST1 in DRGs relieved SNL-induced neuropathic pain. [ABSTRACT FROM AUTHOR]