Topical κ‐opioid receptor agonist asimadoline improves dermatitis in a canine model of atopic dermatitis

Abstract

This prospective, 4‐week, placebo‐controlled, cross‐over study aimed to investigate the efficacy of 1% topical κ‐opioid agonist, asimadoline, in a model of canine atopic dermatitis (AD). Fourteen beagles were challenged with house dust mites every 3–4 days for a total of 9 challenges. Severity of dermatitis was assessed, and pruritus was monitored using GoPro HERO cameras. Pruritus scoring was evaluated at 10 time periods; baseline, 4 h post allergen challenge and the last day of the study on Day 28. Scoring was done blindly by personnel using BORIS software. A global subjective score was also given using a visual analogue scale (VAS). A 4‐week washout period occurred and dogs were crossed‐over, the study was repeated, and the results were analysed using combined data. Gel was applied once daily on inguinal area (0.6 ml/dog). ANOVA showed significant effect of time (p < 0.0001) and group (p = 0.0001) on dermatitis scores. Overall, no statistically significant effect on pruritus was found due to a crossing of scores on Day 17. Overtime the placebo scores increased while the active ingredient showed decrease after first 3 weeks. It is concluded that this approach is promising in dogs with AD and longer studies with more frequent application may be beneficial.

Opioidergic Signaling—A Neglected, Yet Potentially Important Player in Atopic Dermatitis

“…Importantly, by the end of the experiment (day 28), asimadoline significantly improved the Canine Atopic Dermatitis Extent and Severity Index (CADESI) as compared to the placebo control. Interestingly, however, no improvement in the pruritus score was noted [154].…”

Role of kappa‐opioid and mu‐opioid receptors in pruritus: Peripheral and central itch circuits

“…The peripherally restricted KOR agonist HSK21542 significantly reduced itch intensity in a compound 48/80‐induced scratching test in mice; this compound also demonstrated substantial antinociceptive and antiallodynic effects 34 . In a canine AD model employing house dust mite antigen, topical application of the KOR agonist asimadoline substantially reduced dermatitis severity but not pruritus severity, suggesting that its effects may be mediated peripherally at least in part via suppression of inflammation 35 …”

“… 34 In a canine AD model employing house dust mite antigen, topical application of the KOR agonist asimadoline substantially reduced dermatitis severity but not pruritus severity, suggesting that its effects may be mediated peripherally at least in part via suppression of inflammation. 35 …”

New Treatments and Validations for Atopic Dermatitis in Humans After Comparative Approach With Canine Models

“…Similarly, an agonist of K-opioid receptor, asimadoline, has shown promises in a canine study [79] and just recently a synthetic peptide agonist of the kappa opioid receptor has been approved [80]. This medication is for intravenous use, whereas the agonist studied in the canine study was a topical product.…”