Spinal Cord Stimulation Attenuates Itch-Like Behavior and Dermatitis: Contribution of a Spinal Inhibitory Neuronal Ensemble and Associated Reductions in GRPR and Sympathetic Signaling

BACKGROUND: Chronic inflammatory itch is sustained by reciprocal interactions among pruriceptive circuits, scratching-induced skin injury, immune-cell infiltration, and autonomic neuroimmune signaling. Spinal cord stimulation is known to reshape dorsal horn sensory processing, but whether it modulates neuroimmune inflammation during dermatitis-associated itch remains unclear. METHODS: labeling combined with chemogenetic activation or inhibition was used to test the functional contribution of the HF-SCS/TRAP-defined neuronal ensemble. RESULTS: inhibitory neuronal component in the dorsal horn. Chemogenetic reactivation of the HF-SCS/TRAP-defined neuronal ensemble recapitulated the behavioral and cutaneous effects associated with SCS, whereas chemogenetic inhibition impaired the protective efficacy of stimulation. Spinal cord stimulation was also associated with reduced GRPR-related neuronal activation and Grpr expression. Anatomical tracing indicated an association between the HF-SCS/TRAP-defined neuronal ensemble and ChAT+ sympathetic preganglionic neurons, while HF-SCS was accompanied by reduced sympathetic-associated markers in skin and the spinal intermediolateral region. CONCLUSION: inhibitory neurons, while the reductions in GRPR-related activity and sympathetic-associated signaling remain associative findings.