244 Efficacy of kappa-opioid receptor agonist and mu-opioid receptor antagonist to treat itch in imiquimod-induced psoriasis-like dermatitis model

The majority of psoriasis patients suffer from antihistamine-resistant itch. However, therapeutic options to reduce such itch are few, and the pathogenesis of pruritus remains unclear. We previously reported that opioid systems may be involved in the pathogenesis of psoriatic itch. Here, we constructed a psoriasis-like model of scratching behavior and investigated the possible mechanism of itch in this model. Psoriasis-like lesions were induced in the skin of C57BL/6J mice by repeated topical application of imiquimod cream (IMQ) for five days (IMQ-mice) inducing scratching bouts. Oral administration of bepotastine besilate, a histamine H1 receptor antagonist, did not affect the number of scratching bouts in IMQ-mice. We next examined mu-opioid receptor (MOR) and kappa-opioid receptor (KOR) protein expression in epidermis, dorsal root ganglion (DRG) and spinal cord by Western blotting. MOR was increased in the epidermis, DRG and spinal cord of IMQ-mice. In contrast, KOR was reduced in DRG and spinal cord of IMQ-mice. Based on these results, we examined the effects of topical application of naloxone (a MOR antagonist), oral administration of asimadoline hydrochloride (a peripheral KOR agonist) and ICI-199,441 (a central KOR agonist) on scratching behavior in IMQ-mice. The numbers of scratching bouts were significantly decreased in both the topical naloxone and oral ICI-199,441-treated mice without affecting locomotor activity. Meanwhile, asimadoline hydrochloride did not affect the number of scratching bouts in IMQ-mice. In conclusion, scratching behavior is induced in an imiquimod-induced psoriasis-like dermatitis model. In this model, histamine H1 receptor was not involved in scratching behavior. In addition, these results suggest that peripheral MOR and central KOR may be promising as therapeutic targets for psoriatic itch.