title: Spontaneous scratching behavior in MRL/lpr mice, a possible model for pruritus in autoimmune diseases, and antipruritic activity of a novel kappa-opioid receptor agonist nalfurafine hydrochloride.
abstract: Pruritus is a common, distressing and difficult to manage complication of many autoimmune diseases. A suitable animal model of autoimmune disease associated pruritus would contribute to a better understanding of the pathophysiology of this symptom and lead to the development of safe and effective antipruritic agents. We noticed spontaneous scratching behavior in aged MRL/lpr mice, a model of autoimmune disease. This scratching behavior was observed in a specific pathogen-free environment and was more frequent in female mice. In contrast to animal models of dermatitis; NC/Nga mice, the serum IgE and IgG1 levels in MRL/lpr mice were not elevated. These features indicate that this scratching behavior is similar to human autoimmune disease associated pruritus. The antipruritic effects of an antihistamine (chlorpheniramine), an opioid receptor antagonist (naltrexone), and a novel kappa-opioid receptor agonist (nalfurafine hydrochloride [TRK-820]) were evaluated. The frequency of scratching was not reduced by oral administration of chlorpheniramine, suggesting that the behavior is antihistamine-resistant. The oral administration of nalfurafine and subcutaneously administered naltrexone inhibited the scratching behavior without causing gross behavioral changes. In conclusion, MRL/lpr mice scratching behavior is a suitable model of pruritus that occurs in autoimmune diseases, and nalfurafine was shown to be efficacious against this behavior suggesting that it may be beneficial in patients with autoimmune disease associated pruritus.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc. 1111 Tebiro, Kamakura-shi, Kanagawa 248-8555, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Umeuchi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Aoki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nakao
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Itoh
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okano
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyakawa
mesh_terms: D000367:Age Factors; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000150:complications*; D001522:Behavior, Animal / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D009019:Morphinans / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D011537:Pruritus / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012737:Sex Factors; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000982:Antipruritics; D007074:Immunoglobulin G; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820; D007073:Immunoglobulin E; D002744:Chlorpheniramine; D009271:Naltrexone