Spinal-Specific Super Enhancer in Neuropathic Pain

This study investigates the role of super enhancers (SEs) in neuropathic pain, focusing on a spinal-specific SE (SS-SE) that regulates pain by controlling the expression of Ntmt1 and Prrx2 genes. Peripheral nerve injury increases the activity of this SS-SE, leading to higher levels of NTMT1 and PRRX2 in the spinal cord. Blocking SS-SE activity reduces pain hypersensitivity in mice. The findings suggest that targeting SS-SE activity, possibly with BRD4 inhibitors, could offer a new approach for treating neuropathic pain.

• 1
  A spinal-specific super enhancer (SS-SE) was identified that regulates CCI-induced neuropathic pain by driving Ntmt1 and Prrx2 transcription in dorsal horn neurons.
• 2
  Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a BRD4-dependent manner.
• 3
  Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion attenuated nociceptive hypersensitivities in CCI mice.