2. Academic Validation
  3. Lidocaine Ameliorates Psoriasis by Obstructing Pathogenic CGRP Signaling‒Mediated Sensory Neuron‒Dendritic Cell Communication

Lidocaine Ameliorates Psoriasis by Obstructing Pathogenic CGRP Signaling‒Mediated Sensory Neuron‒Dendritic Cell Communication

  • J Invest Dermatol. 2022 Aug;142(8):2173-2183.e6. doi: 10.1016/j.jid.2022.01.002.
Qianqian Yin 1,  Libo Sun 1,  Xiaojie Cai 1,  Fangzhou Lou 1,  Yang Sun 1,  Bin Wang 2,  Bowen Jiang 2,  Lan Bao 2,  Xia Li 3,  Ningjing Song 4,  Sibei Tang 1,  Jing Bai 1,  Zhikai Wang 1,  Yue Wu 1,  Hong Zhou 1,  Hong Wang 1,  Buwei Yu 5,  Qifang Li 5,  Honglin Wang 6
Affiliations

Affiliations

  • 1 Shanghai Institute of Immunology, Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
  • 3 Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Dermatology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of Anesthesiology, Ruijin Hospital and Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Shanghai Institute of Immunology, Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: honglin.wang@sjtu.edu.cn.
PMID: 35032503 DOI: 10.1016/j.jid.2022.01.002
Abstract

Psoriasis is a chronic immune-mediated skin disorder with the nervous system contributing to its pathology. The neurogenic mediators of psoriasis are elusive, and whether the intervention of the cutaneous nervous system can treat psoriasis remains to be determined. In this study, we conducted a pilot study using an epidural injection of lidocaine to treat patients with psoriasis. Lidocaine treatment markedly reduced patients' clinical scores and improved an imiquimod-induced rat model of psoriasis as competent as systemic delivery of a TNF-α antibody. Imiquimod application elicited aberrant cutaneous nerve outgrowth and excessive generation of neuropeptide Calcitonin gene-related peptide from dorsal root ganglion neurons, both of which were inhibited by epidural lidocaine treatment. Single-cell RNA Sequencing unveiled the overrepresentation of Calcitonin gene-related peptide receptors in dermal dendritic cell populations of patients with psoriasis. Through disturbing Calcitonin gene-related peptide signaling, lidocaine inhibited IL-23 production by dendritic cells cocultured with dorsal root ganglion neurons. Thus, epidural nerve block with lidocaine demonstrates an effective therapy for psoriasis, which suppresses both inordinate sensory nerve growth in the inflamed skin and Calcitonin gene-related peptide-mediated IL-23 production from psoriatic dendritic cells.

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