Article ; Online: Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis.
The Journal of allergy and clinical immunology
2023 Volume 152, Issue 4, Page(s) 927–932
Abstract: Background: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD).: Objective: We sought to ... ...
| Abstract | Background: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD). Objective: We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD. Methods: The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch. Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline). Skin ear thickness, histological analysis, flow cytometry, RNA-sequencing, and differential gene expression analyses of mouse ear skin were used to examine the effect of DFK on skin inflammation. Scratching behavior was quantified to measure itch behavior in mice that were topically treated with MC903 for 6 consecutive days; then, mice received a single injection of either DFK (1.0 mg/kg, intraperitoneal injection) or saline. Calcium imaging and single-cell RNA-sequencing were used in mouse dorsal root ganglia neurons to determine the size of the neurons activated with DFK treatment. Statistical significance was determined by Mann-Whitney test, unless otherwise noted. Results: DFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice. In vitro Ca Conclusions: These studies support a potential neuromodulatory role of DFK for reducing itch associated with AD in mice. |
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| MeSH term(s) | Mice ; Animals ; Dermatitis, Atopic/pathology ; Disease Models, Animal ; Mice, Inbred C57BL ; Pruritus/pathology ; Skin/pathology ; Inflammation/drug therapy ; Inflammation/metabolism ; RNA/metabolism |
| Chemical Substances | difelikefalin (NA1U919MRO) ; RNA (63231-63-0) |
| Language | English |
| Publishing date | 2023-07-13 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 121011-7 |
| ISSN | 1097-6825 ; 1085-8725 ; 0091-6749 |
| ISSN (online) | 1097-6825 ; 1085-8725 |
| ISSN | 0091-6749 |
| DOI | 10.1016/j.jaci.2023.06.022 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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