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. 2023 May;180(10):1339-1361.
doi: 10.1111/bph.16012. Epub 2023 Jan 8.

Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons

Pei-Yi Sun  1   2 , Hua-Guo Li  1   2 , Qian-Yue Xu  1   2 , Zhen Zhang  1   2 , Jia-Wen Chen  1   2 , Yi-Hang Shen  1   2 , Xin Qi  3 , Jian-Fei Lu  3 , Yi-Dong Tan  1   2 , Xiao-Xiao Wang  1   2 , Chun-Xiao Li  1   2 , Meng-Ying Yang  1   2 , Yu-Zhi Ma  1   2 , Ying Lu  1   2 , Tian-Le Xu  3 , Jin-Wen Shen  1   2 , Wei-Guang Li  3   4 , Yi-Feng Guo  1   2 , Zhi-Rong Yao  1   2
Affiliations
Free article

Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons

Pei-Yi Sun et al. Br J Pharmacol. 2023 May.
Free article

Abstract

Background and purpose: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism.

Experimental approach: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients.

Key results: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model.

Conclusion and implications: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.

Keywords: atopic dermatitis; lidocaine; neurogenic inflammation; pruritus.

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