Mast Cell-5-HT-HTR2A Axis Involvement in Chronic Itch Induced by SADBE
December 2025
in “
Molecular Pain
”
mast cell 5-hydroxytryptamine 5-HT 5-HT2A HTR2A chronic pruritus squaric acid dibutyl ester SADBE allergic contact dermatitis ACD mast cell stabilizer HTR2A antagonist FcεRIα-KO mice IgE-dependent 5-HT release single-cell RNA sequencing in situ hybridization sensory neurons serotonin itch antihistamine allergy RNA sequencing
TLDR Targeting the MC-5-HT-HTR2A axis may help treat chronic itching.
This study investigates the role of the mast cell-derived 5-hydroxytryptamine (5-HT) and its receptor 5-HT2A (HTR2A) in chronic pruritus induced by squaric acid dibutyl ester (SADBE) in a mouse model of allergic contact dermatitis (ACD). The research demonstrates that SADBE triggers mast cell recruitment and 5-HT release, leading to persistent itching. Pharmacological interventions using a mast cell stabilizer and HTR2A antagonist, as well as experiments with FcεRIα-KO mice, confirmed the involvement of mast cell/IgE-dependent 5-HT release in pruritus. Single-cell RNA sequencing and in situ hybridization showed that HTR2A is expressed in specific subsets of sensory neurons. The study concludes that the MC-5-HT-HTR2A axis plays a crucial role in chronic pruritus in SADBE-induced ACD, suggesting that targeting this axis could be an effective therapeutic strategy.
