Persistent pain signaling and stress response in a mouse model of inflammatory low back pain

Abstract. Introduction:. Chronic low back pain (LBP) is linked to dysfunction in both peripheral and central nervous systems and is a risk factor of psychiatric disorders such as depression. However, pain-related signaling in sensory and central neurons during chronic LBP, and its impact on stress-i...

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Main Authors: Hiroaki Motohashi, Yasuhito Yamaji, Kazunari Mori, Sena Washizu, Oki Hoshino, Kotone Fujimoto, Seiji Kanazawa, Yoshihiko Minegishi, Noriyasu Ota, Takuya Mori, Eri Segi-Nishida
Format: Article
Language:English
Published: Wolters Kluwer 2025-08-01
Series:PAIN Reports
Online Access:http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001300
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author Hiroaki Motohashi
Yasuhito Yamaji
Kazunari Mori
Sena Washizu
Oki Hoshino
Kotone Fujimoto
Seiji Kanazawa
Yoshihiko Minegishi
Noriyasu Ota
Takuya Mori
Eri Segi-Nishida
author_facet Hiroaki Motohashi
Yasuhito Yamaji
Kazunari Mori
Sena Washizu
Oki Hoshino
Kotone Fujimoto
Seiji Kanazawa
Yoshihiko Minegishi
Noriyasu Ota
Takuya Mori
Eri Segi-Nishida
author_sort Hiroaki Motohashi
collection DOAJ
description Abstract. Introduction:. Chronic low back pain (LBP) is linked to dysfunction in both peripheral and central nervous systems and is a risk factor of psychiatric disorders such as depression. However, pain-related signaling in sensory and central neurons during chronic LBP, and its impact on stress-induced emotional behaviors, remains poorly understood. Objectives:. The aim of this study was to investigate persistent changes in pain-related and inflammation-related signaling in an inflammatory LBP mouse model and assess its influence on stress-related behaviors. Methods:. An LBP-like condition was induced by administering complete Freund adjuvant to the lumbar region in mice. Behavioral assessments included gait analysis and mechanical sensitivity testing. Gene expression and immunohistological changes in the dorsal root ganglia (DRG), spinal cord, and brain regions were examined. Chronic social defeat stress (CSDS) was used to evaluate stress susceptibility and emotion-related behavior. Results:. Complete Freund adjuvant–induced lumbar inflammation led to delayed onset of LBP-like behaviors, including impaired gait and hindpaw hypersensitivity, persisting into the chronic phase. Expression of inflammatory and pain-related genes was significantly elevated in the DRG and spinal cord in the lumbar region. Increased microglial activation and reduced Bdnf expression in the hippocampus were observed, accompanied by impaired hippocampal neurogenic process. Mice with LBP-like conditions exhibited heightened avoidance behavior following CSDS and an exaggerated hippocampal stress response. Conclusion:. Chronic inflammation–induced LBP disrupts both peripheral and central neural function and may contribute to increased stress susceptibility and depression-like behaviors.
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spelling doaj-art-368575b593ea4e418cee7c26c44cd8812025-08-20T02:48:16ZengWolters KluwerPAIN Reports2471-25312025-08-01104e130010.1097/PR9.0000000000001300PR90000000000001300Persistent pain signaling and stress response in a mouse model of inflammatory low back painHiroaki Motohashi0Yasuhito Yamaji1Kazunari Mori2Sena Washizu3Oki Hoshino4Kotone Fujimoto5Seiji Kanazawa6Yoshihiko Minegishi7Noriyasu Ota8Takuya Mori9Eri Segi-Nishida10a Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japana Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, Japana Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, Japana Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, Japanb Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanAbstract. Introduction:. Chronic low back pain (LBP) is linked to dysfunction in both peripheral and central nervous systems and is a risk factor of psychiatric disorders such as depression. However, pain-related signaling in sensory and central neurons during chronic LBP, and its impact on stress-induced emotional behaviors, remains poorly understood. Objectives:. The aim of this study was to investigate persistent changes in pain-related and inflammation-related signaling in an inflammatory LBP mouse model and assess its influence on stress-related behaviors. Methods:. An LBP-like condition was induced by administering complete Freund adjuvant to the lumbar region in mice. Behavioral assessments included gait analysis and mechanical sensitivity testing. Gene expression and immunohistological changes in the dorsal root ganglia (DRG), spinal cord, and brain regions were examined. Chronic social defeat stress (CSDS) was used to evaluate stress susceptibility and emotion-related behavior. Results:. Complete Freund adjuvant–induced lumbar inflammation led to delayed onset of LBP-like behaviors, including impaired gait and hindpaw hypersensitivity, persisting into the chronic phase. Expression of inflammatory and pain-related genes was significantly elevated in the DRG and spinal cord in the lumbar region. Increased microglial activation and reduced Bdnf expression in the hippocampus were observed, accompanied by impaired hippocampal neurogenic process. Mice with LBP-like conditions exhibited heightened avoidance behavior following CSDS and an exaggerated hippocampal stress response. Conclusion:. Chronic inflammation–induced LBP disrupts both peripheral and central neural function and may contribute to increased stress susceptibility and depression-like behaviors.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001300
spellingShingle Hiroaki Motohashi
Yasuhito Yamaji
Kazunari Mori
Sena Washizu
Oki Hoshino
Kotone Fujimoto
Seiji Kanazawa
Yoshihiko Minegishi
Noriyasu Ota
Takuya Mori
Eri Segi-Nishida
Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
PAIN Reports
title Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
title_full Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
title_fullStr Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
title_full_unstemmed Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
title_short Persistent pain signaling and stress response in a mouse model of inflammatory low back pain
title_sort persistent pain signaling and stress response in a mouse model of inflammatory low back pain
url http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001300
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