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Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Spinal Cord Stimulation Attenuates Itch-Like Behavior and Dermatitis: Contribution of a Spinal Inhibitory Neuronal
Zi Wang1, Sihan Chen2, Huimin Zhu2
1Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China; Yangzhou University Medical College, Yangzhou, Jiangsu, China.
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:
Using acute pruritogen-evoked itch and DNFB-induced chronic dermatitis models in mice, we examined the effects of low- and high-frequency spinal cord stimulation on itch-like behavior, skin inflammation, spinal GRPR-associated neuronal activation, and sympathetic-associated neuroimmune changes. Activity-dependent FosTRAP2 labeling combined with chemogenetic activation or inhibition was used to test the functional contribution of the HF-SCS/TRAP-defined neuronal ensemble.
Results:
Spinal cord stimulation reduced pruritogen-evoked licking/biting and chronic DNFB-associated itch-like behavior, accompanied by decreased epidermal hyperplasia, T-cell infiltration, and IL-1β/TNF-α-associated inflammatory signals in lesional skin. HF-SCS increased c-Fos activity within a prominent Pax2+ 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:
These findings identify spinal cord stimulation as a preclinical neuromodulatory approach that attenuates dermatitis-associated itch and cutaneous neuroinflammation. The data support a functional contribution of the HF-SCS/TRAP-defined neuronal ensemble, which is enriched in Pax2+ inhibitory neurons, while the reductions in GRPR-related activity and sympathetic-associated signaling remain associative findings.
