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

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.

• Authors: Qianqian Yin, Libo Sun, Xiaojie Cai, Fangzhou Lou, Yang Sun, Bin Wang, Bowen Jiang, Lan Bao, Xia Li, Ningjing Song, Sibei Tang, Jing Bai, Zhikai Wang, Yue Wu, Hong Zhou, Hong Wang, Buwei Yu, Qifang Li, Honglin Wang
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 142 Issue 8 Pg. 2173-2183.e6 (08 2022) ISSN: 1523-1747 [Electronic] United States
• PMID: 35032503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-23
• Lidocaine
• Calcitonin Gene-Related Peptide
• Imiquimod

Topics

• Animals
• Calcitonin Gene-Related Peptide (metabolism)
• Cell Communication
• Dendritic Cells
• Imiquimod (adverse effects)
• Interleukin-23
• Lidocaine (therapeutic use)
• Pilot Projects
• Psoriasis (chemically induced, drug therapy)
• Rats
• Sensory Receptor Cells