{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:15:16Z","timestamp":1788513316845,"version":"build-2803163510"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p>Osteoarthritis is a leading cause of chronic musculoskeletal pain, but pain severity is not fully explained by cartilage loss or radiographic damage. Neuropeptide Y is a multifunctional neuropeptide with receptor- and compartment-dependent effects on nociceptive signaling, sympathetic activity, immune regulation, and skeletal remodeling. Direct osteoarthritis-specific evidence links synovial-fluid neuropeptide Y to pain in some human knee osteoarthritis cohorts, NPY2R signaling to chondrocyte hypertrophy and matrix catabolism, and osteocyte-derived neuropeptide Y to experimental osteoarthritis remodeling. By contrast, proposed effects on synovial fibroblast phenotypes, macrophage polarization, central sensitization, and gut-joint communication are supported mainly by mechanistically adjacent non-osteoarthritis models and remain hypothesis-generating. This review synthesizes current evidence with a pain-centered and translational focus, emphasizing receptor specificity, evidence source, and disease context. Neuropeptide Y is best viewed as one candidate node within broader nociceptive, inflammatory, vascular, metabolic, and biomechanical networks rather than as a primary or exclusive driver of osteoarthritis. Translation will require receptor-selective and tissue-selective strategies, local delivery systems, validated multi-marker panels, and phenotype-stratified studies that distinguish pain-related from structure-related effects.<\/jats:p>","DOI":"10.3389\/fpain.2026.1884062","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:34:49Z","timestamp":1788510889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropeptide Y signaling in osteoarthritis pain: neuroimmune mechanisms, joint remodeling, and translational opportunities"],"prefix":"10.3389","volume":"7","author":[{"given":"Heng","family":"Qiu","sequence":"first","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"Affiliated Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, 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