{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:39:26Z","timestamp":1793691566711,"version":"4.5.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"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. Immunol."],"abstract":"<jats:p>Pain in osteoarthritis (OA) is not explained adequately by cartilage loss or radiographic severity. Synovial inflammation, tissue damage, and neural plasticity interact across the joint, dorsal root ganglia, spinal cord, and brain to shape the intensity and persistence of symptoms. This mini review examines the synovium as an immune niche in OA pain and follows the signals that connect activated macrophages, fibroblast-like synoviocytes, mast cells, T cells, and damaged chondrocytes with nociceptor sensitization. Cytokines, chemokines, prostaglandins, nerve growth factor, complement fragments, and damage-associated molecular patterns can lower nociceptor thresholds and alter TRP, Piezo, and voltage-gated sodium channel activity. Sensory neurons, in turn, release neuropeptides that affect vascular permeability and immune-cell behavior, creating a bidirectional amplification circuit. Persistent peripheral input may recruit dorsal root ganglion macrophages and activate spinal microglia and astrocytes, although direct evidence for specific central immune mechanisms in human OA remains limited. Therapeutic translation therefore requires more than generalized anti-inflammatory treatment. Mechanism-informed stratification integrating synovitis imaging, soluble biomarkers, quantitative sensory testing, and clinical pain features may help distinguish inflammatory, structural, and nociplastic contributions and guide rational combinations of local immune modulation and neural targeting.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1924378","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:00:41Z","timestamp":1788346841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuroimmune crosstalk in osteoarthritis pain: from synovial inflammation to pain sensitization"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhongyan","family":"Mao","sequence":"first","affiliation":[{"name":"Shandong Key Laboratory of Biomechanics, Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University","place":["Jinan, Shandong, 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