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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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| 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. |
| format | Article |
| id | doaj-art-84e3b2bce9ce477382f26f40e4f39bd2 |
| institution | Kabale University |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| 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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