Spinal signatures of entrenched and treated neuropathic pain in male mice

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.