4.7 Article

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

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BRITISH JOURNAL OF PHARMACOLOGY
卷 180, 期 10, 页码 1339-1361

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WILEY
DOI: 10.1111/bph.16012

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atopic dermatitis; lidocaine; neurogenic inflammation; pruritus

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This study found that lidocaine can alleviate itch and skin lesions in atopic dermatitis by blocking certain subpopulations of sensory neurons. It also suggests that lidocaine may be a potential treatment for atopic dermatitis.
Background and PurposeAtopic 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 ApproachPharmacological 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 ResultsLidocaine 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-V 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(V)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 ImplicationsNa(V)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.

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