{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:04:24Z","timestamp":1786122264345,"version":"build-2736575974"},"reference-count":211,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dent. J.","Dentistry Journal"],"abstract":"<jats:p>Temporomandibular disorders (TMD) comprise a heterogeneous group of pain and dysfunction conditions involving the temporomandibular joint, masticatory muscles, and related structures. Although occlusal interference has long been discussed in relation to TMD, current evidence does not support an occlusion-centered etiological model for most patients. Within the contemporary biopsychosocial framework embodied by the Diagnostic Criteria for Temporomandibular Disorders (DC\/TMD), occlusal interference is better regarded as one of several potential peripheral biomechanical inputs that may interact with individual pain susceptibility, parafunctional loading, inflammatory status, and psychosocial factors. This review synthesizes evidence on how peripheral biomechanical and inflammatory inputs may engage masticatory muscle\u2013nerve signaling, trigeminal nociceptor activation, and neurogenic inflammation. We discuss altered masticatory muscle activity, proprioceptive and nociceptive afferent signaling, neuropeptide release, neurovascular and mast cell\u2013nerve interactions, and glial activation within trigeminal pain pathways. Molecular mechanisms, including TRP channel and P2X3 receptor activation, voltage-gated ion channel dysregulation, MAPK, PI3K\/Akt\/mTOR, cAMP\/PKA\/CREB signaling, and epigenetic regulation, are reviewed as candidate pathways linking peripheral input to pain-related plasticity. These mechanisms are further considered in relation to hyperalgesia, mechanical allodynia, pain memory, emotional and cognitive modulation, and sex-related differences in pain processing. Finally, we evaluate translational implications, including mechanism-oriented animal models, exploratory biomarkers, human-derived experimental systems, and mechanism-informed interventions, while emphasizing their current limitations. Overall, this review proposes a cautious mechanistic framework in which peripheral inputs may contribute to TMD-related pain amplification in selected contexts, but clinical translation requires validated phenotyping, longitudinal evidence, and integration with conservative, reversible, and patient-centered standard-of-care management.<\/jats:p>","DOI":"10.3390\/dj14080495","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:14:28Z","timestamp":1786094068000},"page":"495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Muscle\u2013Nerve Signaling and Neurogenic Inflammation in Temporomandibular Disorders: Potential Contributions of Occlusal Interference and Other Peripheral Triggers"],"prefix":"10.3390","volume":"14","author":[{"given":"Yi","family":"Xia","sequence":"first","affiliation":[{"name":"School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingze","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Affiliated Hospital of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","first-page":"52","article-title":"Temporomandibular Disorders: Rapid Evidence Review","volume":"107","author":"Matheson","year":"2023","journal-title":"Am. 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