Spinal signatures of entrenched and treated neuropathic pain in male mice [scRNA-seq]

For chronic pain caused by peripheral nerve injury, sensory neuron damage leads to changes in spinal pain transduction, where enhanced excitatory and/or loss of inhibitory pathways can drive pain diseases. At the cellular level, the transcriptional changes occurring in entrenched chronic pain are largely unknown.

Here we use single nuclei and spatial transcriptomic approaches to investigate the cellular and molecular causes of entrenched and treated neuropathic pain. Our data show that nerve injury leads to broad upregulation of spinal synaptic and excitatory pathways in dorsal neuronal and glial populations. We confirm these core populations are conserved in the human spinal cord, and show an effective pain therapy acts by dampening these neuropathic transcriptional programs.