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Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2023 May; Vol. 180 (10), pp. 1339-1361. Date of Electronic Publication: 2023 Jan 08. - Publication Year :
- 2023
-
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.<br />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.<br />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 Na <subscript>V</subscript> 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 Na <subscript>V</subscript> 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.<br />Conclusion and Implications: Na <subscript>V</subscript> 1.8 <superscript>+</superscript> 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.<br /> (© 2022 British Pharmacological Society.)
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 180
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 36521846
- Full Text :
- https://doi.org/10.1111/bph.16012