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Study · Animal study (in vivo) · mouse · 2023

3 results

Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis.

Tamari M, Zamidar L, Ver Heul AM, Nograles K, Goncalves J, Guttman-Yassky E, Lebwohl M, Kim BS

The Journal of allergy and clinical immunology13 Jul 2023Cited by 13 (Europe PMC)

PMID37453613 (opens in a new tab)DOI10.1016/j.jaci.2023.06.022 (opens in a new tab)PepBankPUB-37453613
Publisher pagePubMedAsk about this study
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Summary

BackgroundTherapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD).ObjectiveWe sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD.MethodsThe 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.ResultsDFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice. In vitro Ca2+ influx trace of dorsal root ganglia suggested that a major target for DFK is the larger-diameter mechanoreceptors (eg, Aꞵ-fibers), rather than small-diameter pruriceptive C-fibers.ConclusionsThese studies support a potential neuromodulatory role of DFK for reducing itch associated with AD in mice.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with MC903-induced dermatitis, difelikefalin rapidly suppressed itch compared with saline.

    In plain wordsIn mice with dermatitis, difelikefalin rapidly reduced itch compared with saline.

    Peptide
    Difelikefalin
    Outcome
    DecreaseItch and scratching
    Study

    mousen: not reported in source

    MC903-induced atopic dermatitis in C57BL/6 mice
    Comparator
    Saline vehicle
    Outcome group
    Skin and hair · Skin and wound
    Studied dose
    1.0 mg/kg · intraperitoneal · single injectionAs given in this study (mouse).

    Source sentences

    Summary
    DFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice.
    3 context sentences
    Summary · context
    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.
    Summary · context
    The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch.
    Summary · context
    Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline).
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with MC903-induced dermatitis, difelikefalin did not alter AD-like skin inflammation compared with vehicle.

    In plain wordsIn mice with dermatitis, difelikefalin did not change skin inflammation compared with vehicle.

    Peptide
    Difelikefalin
    Outcome
    No significant changeAD-like skin inflammation
    Study

    mousen: not reported in source

    MC903-induced atopic dermatitis in C57BL/6 mice
    Comparator
    Saline vehicle
    Outcome group
    Inflammation markers · Skin and wound
    Studied dose
    0.5 mg/kg twice daily · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    DFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice.
    2 context sentences
    Summary · context
    The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch.
    Summary · context
    Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline).
  3. 03LabIn vitro (cells)Mechanism

    In mouse dorsal root ganglia, calcium influx traces suggested that difelikefalin mainly targeted larger mechanoreceptors rather than small pruriceptive C-fibers.

    In plain wordsIn lab tests with mouse neurons, calcium signals suggested difelikefalin mainly targeted larger mechanoreceptors rather than small itch-sensing fibers.

    Peptide
    Difelikefalin
    Outcome
    Not applicableNeuronal calcium influx target
    Study

    mousen: not reported in source

    Mouse dorsal root ganglia neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro Ca2+ influx trace of dorsal root ganglia suggested that a major target for DFK is the larger-diameter mechanoreceptors (eg, Aꞵ-fibers), rather than small-diameter pruriceptive C-fibers.
    1 context sentence
    Summary · context
    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.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:35 UTC

    First added · source update from Europe PMC

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