{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:26:53Z","timestamp":1790508413832,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06168"],"award-info":[{"award-number":["23K06168"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a leading cause of chronic pain and disabilities. Current treatments offer limited efficacy and are often associated with adverse effects. Therefore, novel therapeutic strategies are urgently needed. Mesenchymal stem cell\u2010conditioned medium (MSC\u2010CM) possesses immunomodulatory properties and has been shown to suppress macrophage (M\u03a6) activity, which plays a key role in arthritis pain. However, the effect of MSC\u2010CM\u2010mediated M\u03a6 regulation on arthritis\u2010induced pain remains unclear. In this study, we investigated the analgesic effects of MSC\u2010CM in a mouse model of adjuvant\u2010induced arthritis (AIA), established by the injection of complete Freund's adjuvant (CFA), and examined the involvement of M\u03a6s in mediating these effects. MSC\u2010CM was administered as a single intravenous injection via the tail vein 1 d after the CFA injection. Mechanical and thermal hyperalgesia were evaluated using von Frey filament and the Hargreaves test, respectively. MSC\u2010CM significantly alleviated both mechanical and thermal hyperalgesia but had no effect during the recovery phase. On Day 3 post\u2010CFA injection, when the analgesic effect was most pronounced, flow cytometric analysis revealed that MSC\u2010CM selectively reduced pro\u2010inflammatory M1 M\u03a6s at the site of inflammation without affecting pan\u2010M\u03a6s or anti\u2010inflammatory M2 M\u03a6 populations. Additionally, depletion of M\u03a6s using clodronate liposomes attenuated hyperalgesia in AIA mice. These findings indicate that hyperalgesia in AIA mice was M\u03a6\u2010dependent and that MSC\u2010CM exerted its antihyperalgesic effects by suppressing M\u03a6 activation at inflammatory sites, highlighting its potential as a novel therapeutic approach for inflammatory pain.<\/jats:p>","DOI":"10.1111\/ejn.70296","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:56:38Z","timestamp":1761656198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Potential of Mesenchymal Stem Cell\u2010Conditioned Medium via Macrophage Subset Regulation in a Mouse Model of Arthritis\u2010Associated Pain"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1253-5523","authenticated-orcid":false,"given":"Wataru","family":"Nemoto","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Faculty of Pharmaceutical Sciences Tohoku Medical and Pharmaceutical University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Regulatory Affairs Promotion Division ROHTO Pharmaceutical Co. 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