Summary
Background
It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear.
Objective
To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action.
Methods
In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis‐like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow‐derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application.
Results
Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL‐12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre‐incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl.
Conclusions and Clinical Relevance
These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.
Disclosure of potential conflict of interest: W. Janssen's institution received a grant from Baralta. J. van Montfrans's institution has received a grant for the work under consideration from Shire, The Netherlands and consultancy fees as well as payment for lectures for other works from Shire. The rest of the authors declare that they have no relevant conflicts of interest.
IntroductionRodent primary sensory neurons are commonly used for studying itch and pain neurophysiology, but translation from rodents to larger mammals and humans is not direct and requires further validation to make correlations.MethodsThis study developed a primary canine sensory neuron culture from dorsal root ganglia (DRG) excised from cadaver dogs. Additionally, the canine DRG cell cultures developed were used for single‐cell ratiometric calcium imaging, with the activation of neurons to the following pruritogenic and algogenic substances: histamine, chloroquine, canine protease‐activated receptor 2 (PAR2) activating peptide (SLIGKT), compound 48/80, 5‐hydroxytryptamine receptor agonist (5‐HT), bovine adrenal medulla peptide (BAM8‐22), substance P, allyl isothiocyanate (AITC), and capsaicin.ResultsThis study demonstrates a simple dissection and rapid processing of DRG collected from canine cadavers used to create viable primary sensory neuron cultures to measure responses to pruritogens and algogens.ConclusionRatiometric calcium imaging demonstrated that small‐diameter canine sensory neurons can be activated by multiple stimuli, and a single neuron can react to both a pruritogenic stimulation and an algogenic stimulation.
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