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Pain Res."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study evaluated the effects of low-intensity muscle contraction exercise on pain sensitivity, peripheral pathology, and central sensitization in the spinal dorsal horn in a rat model of end-stage knee osteoarthritis (OA) induced by monosodium iodoacetate (MIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty-two male Wistar rats were assigned to three groups: OA, Exercise, and Sham. The Exercise group underwent quadriceps muscle contractions induced by electrical stimulation (50\u2005Hz, 250 \u00b5s, 2\u20133\u2005mA) with a duty cycle of 1:2 (2\u2005s On, 4\u2005s Off) for 20\u2005min daily, five days per week, from day 29 to day 56 post-MIA administration. Pain sensitivity was assessed by measuring knee joint pressure pain thresholds (PPT) and paw withdrawal thresholds using von Frey filaments. Histological and immunohistochemical analyses of the knee joint and spinal cord included toluidine blue staining, tartrate-resistant acid phosphatase staining, and markers for CD68, CD11c, CD206, osteoclasts, nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), and phosphorylated NR1 (pNR1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Knee joint PPTs were significantly higher in the Exercise group after day 35, accompanied by reductions in CD68-, CD11c-positive cells, NGF-positive cells, CGRP-positive fibers, osteoclasts, and pNR1-positive cells, as well as an increase in CD206-positive cells, compared to the OA group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Despite no significant changes in cartilage or subchondral bone degeneration, these findings suggest that low-intensity muscle contraction exercise alleviates pain sensitivity by modulating peripheral pathology and central sensitization. This study highlights the potential of therapeutic exercise as a strategy for OA pain management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpain.2025.1644177","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:27:10Z","timestamp":1759123630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Low-intensity muscle contraction exercise reduces pain sensitivity by modulating peripheral pathology and spinal sensitization in end-stage knee osteoarthritis rats"],"prefix":"10.3389","volume":"6","author":[{"given":"Satoko","family":"Motokawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayumi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Okita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"B1","first-page":"32","volume-title":"Management of Osteoarthritis of the Knee (Non-Arthroplasty) Evidence-Based Clinical Practice Guideline","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B3","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1136\/annrheumdis-2017-212662","article-title":"EULAR recommendations for the health professional\u2019s approach to pain management in inflammatory arthritis and osteoarthritis","volume":"77","author":"Geenen","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1002\/art.40101","article-title":"Effects of treadmill exercise on advanced osteoarthritis pain in rats","volume":"69","author":"Allen","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.lfs.2017.05.011","article-title":"Exercise reverses pain-related weight asymmetry and differentially modulates trabecular bone microarchitecture in a rat model of osteoarthritis","volume":"180","author":"Cormier","year":"2017","journal-title":"Life Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1002\/acr.22825","article-title":"Efficacy of preoperative progressive resistance training on postoperative outcomes in patients undergoing total knee arthroplasty","volume":"68","author":"Skoffer","year":"2016","journal-title":"Arthritis Care Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1007\/s00167-016-3985-5","article-title":"High-intensity preoperative training improves physical and functional recovery in the early post-operative periods after total knee arthroplasty: a randomized controlled trial","volume":"25","author":"Calatayud","year":"2017","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"B8","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.pmrj.2012.04.012","article-title":"The effect of a prehabilitation exercise program on quadriceps strength for patients undergoing total knee arthroplasty: a randomized controlled pilot study","volume":"4","author":"Mckay","year":"2012","journal-title":"PM R"},{"key":"B9","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1002\/art.23823","article-title":"Does knee malalignment mediate the effects of quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? 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