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<p>Chronic pain caused by peripheral nerve injury involves altered spinal pain transduction, where enhanced excitatory and/or reduced inhibitory pathways can drive pain. The cellular transcriptional changes that sustain entrenched neuropathic pain remain poorly understood. Here we use single-nucleus and spatial transcriptomic approaches in male mice to investigate spinal cellular and molecular programs associated with entrenched and treated neuropathic pain. We show that nerve injury leads to broad upregulation of synaptic and excitatory pathways in dorsal neuronal and glial populations. We confirm that these core populations are conserved in the human spinal cord, and show that an effective pain therapy dampens neuropathic transcriptional programs. These data identify spinal cell populations and pathways associated with neuropathic pain states and therapeutic reversal.</p>

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Spinal signatures of entrenched and treated neuropathic pain in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月15日

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  • Lipin Loo,
  • Kazuma Fujikake,
  • Bryony L. Winters,
  • Grace Cunliffe,
  • Sasha Saad,
  • Teleri Clark,
  • Zina Hamoudi,
  • John Manion,
  • Leslie Caron,
  • Olivia C. Davis,
  • Diana Tavares-Ferreira,
  • Stephanie Shiers,
  • Joseph E. Powell,
  • Theodore J. Price,
  • G. Gregory Neely

摘要

Chronic pain caused by peripheral nerve injury involves altered spinal pain transduction, where enhanced excitatory and/or reduced inhibitory pathways can drive pain. The cellular transcriptional changes that sustain entrenched neuropathic pain remain poorly understood. Here we use single-nucleus and spatial transcriptomic approaches in male mice to investigate spinal cellular and molecular programs associated with entrenched and treated neuropathic pain. We show that nerve injury leads to broad upregulation of synaptic and excitatory pathways in dorsal neuronal and glial populations. We confirm that these core populations are conserved in the human spinal cord, and show that an effective pain therapy dampens neuropathic transcriptional programs. These data identify spinal cell populations and pathways associated with neuropathic pain states and therapeutic reversal.