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Analgesic agents and corticosteroids are often used to supplement DMARDs for pain relief but lack disease modifying properties, and their sustained use carries adverse risks. In this work, we characterized the progression of pain sensitivity in the SKG mouse model of RA and evaluated the potential therapeutic interventions. Male and female SKG mice, after systemic mannan injection, developed a mechanical pain phenotype and joint swelling, with a strong inverse correlation between clinical arthritis scores and pain thresholds. To test potential interventions for pain alleviation, we evaluated all\u2010trans retinoic acid (ATRA)\u2010loaded poly(lactic\u2010co\u2010glycolic acid) microparticles (ATRA\u2010PLGA MP) administered via intra\u2010articular injection, which we have previously demonstrated to be disease\u2010modifying. The pain and inflammation patterns assessed by the von Frey test and clinical scoring showed ATRA\u2010PLGA MP monotherapy reduced inflammation and alleviated mechanical allodynia in arthritic SKG mice, an effect that was amplified by combination treatments with standard\u2010of\u2010care agents. In early\u2010stage arthritis, co\u2010administration with cytotoxic T\u2010lymphocyte\u2010associated protein (CTLA)\u20104\u2010Ig, clinically known as abatacept, delayed disease progression and sustained the reduction of mechanical allodynia. In established arthritis, sequential treatment with the corticosteroid dexamethasone (Dex) reduced cumulative disease burden and reduced mechanical allodynia. These findings highlight the potential of combining ATRA\u2010PLGA MP with standard\u2010of\u2010care treatments as a potential strategy to enhance the efficacy and durability of disease modification and pain alleviation for arthritis management.<\/jats:p>","DOI":"10.1002\/btm2.70054","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T10:30:21Z","timestamp":1753957821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disease modifying biomaterials for modulating mechanical allodynia in a preclinical model of rheumatoid arthritis"],"prefix":"10.1002","volume":"10","author":[{"given":"Maksim","family":"Dolmat","sequence":"first","affiliation":[{"name":"Department of Chemical and Nano Engineering University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Borges 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzio","family":"Bottini","sequence":"additional","affiliation":[{"name":"Kao Autoimmunity Institute and Division of Rheumatology Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-5732","authenticated-orcid":false,"given":"Nisarg J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Chemical and Nano Engineering University of California San Diego  La Jolla California 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