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 language | English (US) |
|---|---|
| Pages (from-to) | 133-139 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 518 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Aug 22 2005 |
| Externally published | Yes |
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Keywords
- κ-opioid agonist
- MRL/lpr mouse
- Pruritus
- Scratching behavior
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
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. / Umeuchi, Hideo; Kawashima, Yumi; Aoki, Christopher A.; Kurokawa, Takahiro; Nakao, Kaoru; Itoh, Masatoshi; Kikuchi, Kentaro; Kato, Takashi; Okano, Kiyoshi; Gershwin, M. Eric; Miyakawa, Hiroshi.
In: European Journal of Pharmacology, Vol. 518, No. 2-3, 22.08.2005, p. 133-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Umeuchi, Hideo
AU - Kawashima, Yumi
AU - Aoki, Christopher A.
AU - Kurokawa, Takahiro
AU - Nakao, Kaoru
AU - Itoh, Masatoshi
AU - Kikuchi, Kentaro
AU - Kato, Takashi
AU - Okano, Kiyoshi
AU - Gershwin, M. Eric
AU - Miyakawa, Hiroshi
PY - 2005/8/22
Y1 - 2005/8/22
N2 - 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.
AB - 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.
KW - κ-opioid agonist
KW - MRL/lpr mouse
KW - Pruritus
KW - Scratching behavior
UR - http://www.scopus.com/inward/record.url?scp=23644458759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644458759&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.06.019
DO - 10.1016/j.ejphar.2005.06.019
M3 - Article
C2 - 16055114
AN - SCOPUS:23644458759
VL - 518
SP - 133
EP - 139
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -