Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis

Abstract Osteoarthritis of the knee (knee OA) causes chronic pain involving peripheral tissues, the spinal cord, and the brain. Neuropathic pain leads to changes in synaptic plasticity in the anterior cingulate cortex (ACC). However, whether such changes occur in knee OA mice and their association w...

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Main Authors: Ryo Miyake, Manabu Yamanaka, Wataru Taniguchi, Naoko Nishio, Yuki Matsuyama, Takeru Ueno, Yuta Kaimochi, Terumasa Nakatsuka, Hiroshi Yamada
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Molecular Brain
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Online Access:https://doi.org/10.1186/s13041-025-01207-9
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author Ryo Miyake
Manabu Yamanaka
Wataru Taniguchi
Naoko Nishio
Yuki Matsuyama
Takeru Ueno
Yuta Kaimochi
Terumasa Nakatsuka
Hiroshi Yamada
author_facet Ryo Miyake
Manabu Yamanaka
Wataru Taniguchi
Naoko Nishio
Yuki Matsuyama
Takeru Ueno
Yuta Kaimochi
Terumasa Nakatsuka
Hiroshi Yamada
author_sort Ryo Miyake
collection DOAJ
description Abstract Osteoarthritis of the knee (knee OA) causes chronic pain involving peripheral tissues, the spinal cord, and the brain. Neuropathic pain leads to changes in synaptic plasticity in the anterior cingulate cortex (ACC). However, whether such changes occur in knee OA mice and their association with exercise therapy remains unclear. Therefore, this study investigated these aspects using electrophysiological and behavioral approaches. We found no induction of pre- or post-long-term potentiation (LTP) in the ACC of knee OA mice. Application of ZD7288 and zeta inhibitory peptide (ZIP) reduced the amplitude of evoked excitatory postsynaptic currents, indicating pre-existing changes in synaptic plasticity in the ACC. Microinjection of ZD7288 and ZIP improved pain-escape and anxiety-like behaviors. Voluntary running exercise induced pre- and post-LTP and improved these behaviors in knee OA mice. Exercise therapy for knee OA may alter synaptic plasticity in the ACC, contributing to behavioral improvements.
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institution Kabale University
issn 1756-6606
language English
publishDate 2025-08-01
publisher BMC
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series Molecular Brain
spelling doaj-art-84e3b2bce9ce477382f26f40e4f39bd22025-08-24T11:57:54ZengBMCMolecular Brain1756-66062025-08-0118111710.1186/s13041-025-01207-9Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritisRyo Miyake0Manabu Yamanaka1Wataru Taniguchi2Naoko Nishio3Yuki Matsuyama4Takeru Ueno5Yuta Kaimochi6Terumasa Nakatsuka7Hiroshi Yamada8Department of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityDepartment of Orthopaedic Surgery, Wakayama Medical UniversityPain Research Center, Kansai University of Health SciencesDepartment of Orthopaedic Surgery, Wakayama Medical UniversityAbstract Osteoarthritis of the knee (knee OA) causes chronic pain involving peripheral tissues, the spinal cord, and the brain. Neuropathic pain leads to changes in synaptic plasticity in the anterior cingulate cortex (ACC). However, whether such changes occur in knee OA mice and their association with exercise therapy remains unclear. Therefore, this study investigated these aspects using electrophysiological and behavioral approaches. We found no induction of pre- or post-long-term potentiation (LTP) in the ACC of knee OA mice. Application of ZD7288 and zeta inhibitory peptide (ZIP) reduced the amplitude of evoked excitatory postsynaptic currents, indicating pre-existing changes in synaptic plasticity in the ACC. Microinjection of ZD7288 and ZIP improved pain-escape and anxiety-like behaviors. Voluntary running exercise induced pre- and post-LTP and improved these behaviors in knee OA mice. Exercise therapy for knee OA may alter synaptic plasticity in the ACC, contributing to behavioral improvements.https://doi.org/10.1186/s13041-025-01207-9Osteoarthritis of the kneeChronic painSynaptic plasticityAnterior cingulate cortexExercise therapyVoluntary running
spellingShingle Ryo Miyake
Manabu Yamanaka
Wataru Taniguchi
Naoko Nishio
Yuki Matsuyama
Takeru Ueno
Yuta Kaimochi
Terumasa Nakatsuka
Hiroshi Yamada
Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
Molecular Brain
Osteoarthritis of the knee
Chronic pain
Synaptic plasticity
Anterior cingulate cortex
Exercise therapy
Voluntary running
title Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
title_full Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
title_fullStr Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
title_full_unstemmed Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
title_short Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
title_sort voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis
topic Osteoarthritis of the knee
Chronic pain
Synaptic plasticity
Anterior cingulate cortex
Exercise therapy
Voluntary running
url https://doi.org/10.1186/s13041-025-01207-9
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