Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis

Experimental research using canine itch models advanced the development of novel medications that inhibit different itch-induced pathways. This study aimed to investigate the immediate/delayed pruritus responses/behaviors observed after the intradermal administration of recombinant canine interleukin-31 (IL-31) to healthy dogs (intradermal IL-31-induced pruritic model) and the reversal of the induced pruritic behaviors in the same dogs using oral oclacitinib (JAK inhibitor). The itch behaviors were video-recorded for 300 consecutive min, and two blinded investigators reviewed all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in pruritic behaviors, which were significantly reduced after oral oclacitinib administration. Significant delayed pruritic responses at 150-300 min after IL-31 injections were observed, whereas intradermal IL-31 failed to induce acute itch in the dogs within the first 30 min. Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor. Pruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the natural itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic behaviors observed in an intradermal IL-31-induced pruritic model of healthy dogs and the anti-pruritic effect of oclacitinib on said model. In Phase 1, all the dogs were randomized and video-recorded for 300 min after intradermal canine recombinant IL-31 injections (1.75 mu g/kg) and vehicle (phosphate-buffered saline) injections. In Phase 2, all the dogs received oral oclacitinib (0.4-0.6 mg/kg, twice daily for 4 consecutive days and once daily on day 5), with the intradermal IL-31 injection performed on day 5. Two blinded investigators reviewed the pruritic behaviors in all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in the total (p = 0.0052) and local (p = 0.0003) seconds of pruritic behavior compared to the vehicle control. Oral oclacitinib administration significantly reduced the total (p = 0.0011) and local (p = 0.0156) intradermal IL-31-induced pruritic seconds; there was no significant difference in pruritic seconds between the vehicle and oclacitinib within the IL-31 groups. Significant delayed pruritic responses at 150-300 min after IL-31 injections were observed, and intradermal IL-31 failed to induce acute itch (first 30 min). Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor.

Automated summary

Intradermal administration of IL-31 to healthy dogs caused delayed itch responses, which were reduced by oclacitinib, an oral JAK inhibitor.