To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch

Background: Strategies to efficiently control itch require a deep understanding of the underlying mechanisms. Several areas in the brain involved in itch and scratching responses have been postulated, but the central mechanisms that drive pruritic responses are still unknown. Histamine is recognized...

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Main Authors: Sarah Ehling, Ashley Butler, Stephanie Thi, H. Troy Ghashghaei, Wolfgang Bäumer
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:IBRO Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S245183011830044X
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spelling doaj-9e3882380eb242ddb5e49621eaed98792020-11-24T23:24:42ZengElsevierIBRO Reports2451-83012018-12-0156773To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itchSarah Ehling0Ashley Butler1Stephanie Thi2H. Troy Ghashghaei3Wolfgang Bäumer4Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USA; Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany; Corresponding author at: Institute for Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Koserstrasse 20, 14195 Berlin, Germany.Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USA; Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, GermanyBackground: Strategies to efficiently control itch require a deep understanding of the underlying mechanisms. Several areas in the brain involved in itch and scratching responses have been postulated, but the central mechanisms that drive pruritic responses are still unknown. Histamine is recognized as a major mediator of itch in humans, and has been the most frequently used stimulus as an experimental pruritogen for brain imaging of itch. Objective: Histaminergic itch via histamine and the selective histamine H4 receptor (H4R) agonist, ST-1006, recruit brain nuclei through c-fos activation and activate specific areas in the brain. Methods: An acute itch model was established in c-fos-EGFP transgenic mice using ST-1006 and histamine. Coronal brain sections were stained for c-fos immunoreactivity and the forebrain was mapped for density of c-fos + nuclei. Results: Histamine and ST-1006 significantly increased scratching response in c-fos-EGFP mice compared to vehicle controls. Mapping c-fos immunostained brain sections revealed neuronal activity in the cortex, striatum, hypothalamus, thalamus, amygdala, and the midbrain. Conclusions: Histaminergic itch and selective H4R activation significantly increased the density of c-fos + nuclei in the medial habenula (MHb). Thus, the MHb may be a new target to investigate and subsequently develop novel mechanism-based strategies to treat itch and possibly provide a locus for pharmacological control of pruritus. Keywords: c-fos, Itch, Brain, Medial habenula, Histamine H4 receptorhttp://www.sciencedirect.com/science/article/pii/S245183011830044X
collection DOAJ
language English
format Article
sources DOAJ
author Sarah Ehling
Ashley Butler
Stephanie Thi
H. Troy Ghashghaei
Wolfgang Bäumer
spellingShingle Sarah Ehling
Ashley Butler
Stephanie Thi
H. Troy Ghashghaei
Wolfgang Bäumer
To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
IBRO Reports
author_facet Sarah Ehling
Ashley Butler
Stephanie Thi
H. Troy Ghashghaei
Wolfgang Bäumer
author_sort Sarah Ehling
title To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
title_short To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
title_full To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
title_fullStr To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
title_full_unstemmed To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch
title_sort to scratch an itch: establishing a mouse model to determine active brain areas involved in acute histaminergic itch
publisher Elsevier
series IBRO Reports
issn 2451-8301
publishDate 2018-12-01
description Background: Strategies to efficiently control itch require a deep understanding of the underlying mechanisms. Several areas in the brain involved in itch and scratching responses have been postulated, but the central mechanisms that drive pruritic responses are still unknown. Histamine is recognized as a major mediator of itch in humans, and has been the most frequently used stimulus as an experimental pruritogen for brain imaging of itch. Objective: Histaminergic itch via histamine and the selective histamine H4 receptor (H4R) agonist, ST-1006, recruit brain nuclei through c-fos activation and activate specific areas in the brain. Methods: An acute itch model was established in c-fos-EGFP transgenic mice using ST-1006 and histamine. Coronal brain sections were stained for c-fos immunoreactivity and the forebrain was mapped for density of c-fos + nuclei. Results: Histamine and ST-1006 significantly increased scratching response in c-fos-EGFP mice compared to vehicle controls. Mapping c-fos immunostained brain sections revealed neuronal activity in the cortex, striatum, hypothalamus, thalamus, amygdala, and the midbrain. Conclusions: Histaminergic itch and selective H4R activation significantly increased the density of c-fos + nuclei in the medial habenula (MHb). Thus, the MHb may be a new target to investigate and subsequently develop novel mechanism-based strategies to treat itch and possibly provide a locus for pharmacological control of pruritus. Keywords: c-fos, Itch, Brain, Medial habenula, Histamine H4 receptor
url http://www.sciencedirect.com/science/article/pii/S245183011830044X
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