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Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and bone destruction at the joints, causing pain and motor disturbance. Despite the better control of inflammation and joint deformity afforded by modern disease-modifying anti-rheumatic drugs, many pat...

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Autores principales: Oto, Yohsuke, Takahashi, Yukari, Kurosaka, Daitaro, Kato, Fusao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909634/
https://www.ncbi.nlm.nih.gov/pubmed/31831067
http://dx.doi.org/10.1186/s13075-019-2071-z
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author Oto, Yohsuke
Takahashi, Yukari
Kurosaka, Daitaro
Kato, Fusao
author_facet Oto, Yohsuke
Takahashi, Yukari
Kurosaka, Daitaro
Kato, Fusao
author_sort Oto, Yohsuke
collection PubMed
description BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and bone destruction at the joints, causing pain and motor disturbance. Despite the better control of inflammation and joint deformity afforded by modern disease-modifying anti-rheumatic drugs, many patients with RA remain dissatisfied with their treatment, primarily because of sensory-emotional distress. Pre-clinical tests that can evaluate not only the symptoms of arthritis but also the associated pain as sensory-emotional experience are urgently needed. METHODS: Here, we introduce two types of novel methods for evaluation of voluntary behavior in a commonly used model of RA (collagen-induced arthritis; CIA) in male mice. First, spontaneous motor activity was assessed with a running wheel placed in home cages and the number of rotations was continuously recorded in a 12:12-h light environment. Second, temperature preference was assessed by measuring the time spent in either of the floor plates with augmenting (25 to 49 °C) or fixed temperature (25 °C). We also evaluated the effects of tofacitinib on CIA-associated changes in voluntary wheel running and temperature preference. RESULTS: We detected a significant decrease in voluntary wheel running, a significant shift in the distribution of movement in the dark phase, and a significant increase in the time spent in warmer environments than the room temperature in the mice with CIA. These alterations in voluntary behavior have never been described with conventional methods. We also revealed tofacitinib-resistant significant changes in the voluntary behavior and choice of temperature despite significant mitigation of the symptoms of arthritis. CONCLUSIONS: We described for the first time significant alterations of the voluntary behavior of the mice with CIA during the clinical periods, indicating that the overall physical/motivational states and its circadian variation, as well as the specific preference to a certain environmental temperature, are modified in the mice with CIA, as observed in human patients. Some of these did not parallel with the conventional arthritis scores, particularly during the pharmacotherapy suggesting that mice with CIA show not only the peripheral symptoms but also the central consequences. The use of these approaches would also help clarify the biological mechanisms underlying physician-patient discordance in the assessment of RA.
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spelling pubmed-69096342019-12-30 Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis Oto, Yohsuke Takahashi, Yukari Kurosaka, Daitaro Kato, Fusao Arthritis Res Ther Research Article BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and bone destruction at the joints, causing pain and motor disturbance. Despite the better control of inflammation and joint deformity afforded by modern disease-modifying anti-rheumatic drugs, many patients with RA remain dissatisfied with their treatment, primarily because of sensory-emotional distress. Pre-clinical tests that can evaluate not only the symptoms of arthritis but also the associated pain as sensory-emotional experience are urgently needed. METHODS: Here, we introduce two types of novel methods for evaluation of voluntary behavior in a commonly used model of RA (collagen-induced arthritis; CIA) in male mice. First, spontaneous motor activity was assessed with a running wheel placed in home cages and the number of rotations was continuously recorded in a 12:12-h light environment. Second, temperature preference was assessed by measuring the time spent in either of the floor plates with augmenting (25 to 49 °C) or fixed temperature (25 °C). We also evaluated the effects of tofacitinib on CIA-associated changes in voluntary wheel running and temperature preference. RESULTS: We detected a significant decrease in voluntary wheel running, a significant shift in the distribution of movement in the dark phase, and a significant increase in the time spent in warmer environments than the room temperature in the mice with CIA. These alterations in voluntary behavior have never been described with conventional methods. We also revealed tofacitinib-resistant significant changes in the voluntary behavior and choice of temperature despite significant mitigation of the symptoms of arthritis. CONCLUSIONS: We described for the first time significant alterations of the voluntary behavior of the mice with CIA during the clinical periods, indicating that the overall physical/motivational states and its circadian variation, as well as the specific preference to a certain environmental temperature, are modified in the mice with CIA, as observed in human patients. Some of these did not parallel with the conventional arthritis scores, particularly during the pharmacotherapy suggesting that mice with CIA show not only the peripheral symptoms but also the central consequences. The use of these approaches would also help clarify the biological mechanisms underlying physician-patient discordance in the assessment of RA. BioMed Central 2019-12-12 2019 /pmc/articles/PMC6909634/ /pubmed/31831067 http://dx.doi.org/10.1186/s13075-019-2071-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Oto, Yohsuke
Takahashi, Yukari
Kurosaka, Daitaro
Kato, Fusao
Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title_full Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title_fullStr Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title_full_unstemmed Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title_short Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
title_sort alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909634/
https://www.ncbi.nlm.nih.gov/pubmed/31831067
http://dx.doi.org/10.1186/s13075-019-2071-z
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