Imiquimod-induced pruritus in female wild-type and knockin Wistar rats: underscoring behavioral scratching in a rat model for antipruritic treatments.


Journal

BMC research notes
ISSN: 1756-0500
Titre abrégé: BMC Res Notes
Pays: England
ID NLM: 101462768

Informations de publication

Date de publication:
25 Nov 2023
Historique:
received: 26 05 2023
accepted: 16 11 2023
medline: 27 11 2023
pubmed: 26 11 2023
entrez: 25 11 2023
Statut: epublish

Résumé

Animal models of skin disease are used to evaluate therapeutics to alleviate disease. One common clinical dermatological complaint is pruritus (itch), but there is a lack of standardization in the characterization of pre-clinical models and scratching behavior, a key itch endpoint, is often neglected. One such model is the widely used imiquimod (IMQ) mouse model of psoriasis. However, it lacks characterized behavioral attributes like scratching, nor has widely expanded to other species like rats. Given these important attributes, this study was designed to broaden the characterization beyond the expected IMQ-induced psoriasis-like skin inflammatory skin changes and to validate the role of a potential therapeutic agent for pruritus in our genetic rat model. The study included female Wistar rats and genetically modified knockin (humanized proteinase-activated receptor 2 (F2RL1) female rats, with the widely used C57BL/6 J mice as a methodology control for typical IMQ dosing. We demonstrate that the IMQ model can be reproduced in rats, including their genetically modified derivatives, and how scratching can be used as a key behavioral endpoint. We systemically delivered an anti-PAR2 antibody (P24E1102) which reversed scratching bouts-validating this behavioral methodology and have shown its feasibility and value in identifying effective antipruritic drugs.

Identifiants

pubmed: 38007440
doi: 10.1186/s13104-023-06627-1
pii: 10.1186/s13104-023-06627-1
pmc: PMC10675923
doi:

Substances chimiques

Antipruritics 0
Imiquimod P1QW714R7M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

348

Informations de copyright

© 2023. The Author(s).

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Auteurs

Karen Lariosa-Willingham (K)

Teva Pharmaceutical Industries Ltd, Redwood City, CA, 94063, USA. lariosawillingham@gmail.com.

Dmitri Leonoudakis (D)

Teva Pharmaceutical Industries Ltd, Redwood City, CA, 94063, USA.

Florian Simon (F)

Porsolt SAS, ZA de Glatigné, 53940, Le Genest-Saint-Isle, France.

Kendall Walker (K)

Porsolt SAS, ZA de Glatigné, 53940, Le Genest-Saint-Isle, France.

Philippe Guillaume (P)

Porsolt SAS, ZA de Glatigné, 53940, Le Genest-Saint-Isle, France.

Liling Warren (L)

Teva Pharmaceutical Industries Ltd, Redwood City, CA, 94063, USA.

Jennifer Stratton (J)

Teva Pharmaceutical Industries Ltd, Redwood City, CA, 94063, USA.

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Classifications MeSH