Neuropathic Pain-Like Responses in a Chronic CNS Injury Model Are Mediated by Corticospinal-Targeted Spinal Interneurons. Academic Article uri icon

Overview

abstract

  • Chronic neuropathic pain is a persistent and debilitating outcome of traumatic central nervous system injury, affecting up to 80% of individuals. Postinjury pain is refractory to treatments due to the limited understanding of the brain-spinal cord circuits that underlie pain signal processing. The corticospinal tract (CST) plays critical roles in sensory modulation during skilled movements and tactile sensation; however, a direct role for the CST in injury-associated neuropathic pain is unclear. Here we show that complete, selective CST transection at the medullary pyramids leads to hyperexcitability within lumbar deep dorsal horn and hindlimb allodynia-like behavior in chronically injured adult male and female mice. Chemogenetic regulation of CST-targeted lumbar spinal interneurons demonstrates that dysregulation of activity in this circuit underlies the development of tactile allodynia in chronic injury. Our findings shed light on an unrecognized circuit mechanism implicated in CNS injury-induced neuropathic pain and provide a novel target for therapeutic intervention.

publication date

  • July 16, 2025

Research

keywords

  • Interneurons
  • Neuralgia
  • Pyramidal Tracts
  • Spinal Cord
  • Spinal Cord Injuries

Identity

PubMed Central ID

  • PMC12268975

Scopus Document Identifier

  • 105011291653

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.1264-24.2025

PubMed ID

  • 40550694

Additional Document Info

volume

  • 45

issue

  • 29