Spontaneous scratching behavior in MRL/lpr mice, a possible model for pruritus in autoimmune diseases, and antipruritic activity of a novel κ-opioid receptor agonist nalfurafine hydrochloride

Hideo Umeuchi, Yumi Kawashima, Christopher A. Aoki, Takahiro Kurokawa, Kaoru Nakao, Masatoshi Itoh, Kentaro Kikuchi, Takashi Kato, Kiyoshi Okano, M. Eric Gershwin, Hiroshi Miyakawa

Research output: Contribution to journalArticle

27 Scopus citations

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 κ-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.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalEuropean Journal of Pharmacology
Volume518
Issue number2-3
DOIs
StatePublished - Aug 22 2005
Externally publishedYes

Keywords

  • κ-opioid agonist
  • MRL/lpr mouse
  • Pruritus
  • Scratching behavior

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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