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This article reviews the current knowledge of the molecular mechanisms behind\n                    <jats:styled-content style=\"fixed-case\">TMJ<\/jats:styled-content>\n                    internal derangements. A non\u2010systematic search was carried out in PubMed, Embase and the Cochrane library for studies regarding pathophysiological mechanisms behind internal derangements focusing on pain\u2010mediating inflammatory and cartilage\u2010degrading molecules. Recent data suggest that release of cytokines may be the key event for pain and cartilage destruction in\n                    <jats:styled-content style=\"fixed-case\">TMJ<\/jats:styled-content>\n                    internal derangements. Cytokines promote the release of matrix metalloproteinases (\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    s), and due to hypoxia, vascular endothelial growth factor (\n                    <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\n                    ) is released. This activates chondrocytes to produce\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    s and reduce their tissue inhibitors (\n                    <jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\n                    s) as well as the recruitment of osteoclasts, ultimately leading to cartilage and bone resorption. Also, proteoglycans have an important role in this process. Several cytokines,\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    s,\n                    <jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\n                    s and\n                    <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\n                    have been identified in higher concentrations in the\n                    <jats:styled-content style=\"fixed-case\">TMJ<\/jats:styled-content>\n                    synovial fluid of patients with painful internal derangements and shown to be associated with the degree of degeneration. Other molecules that show elevated levels include hyaluronic acid synthase, disintegrin and metalloproteinase with thrombospondin motifs (\n                    <jats:styled-content style=\"fixed-case\">ADAMT<\/jats:styled-content>\n                    s), aggrecan, fibromodulin, biglycan and lumican. Taken together, more or less pronounced inflammation of\n                    <jats:styled-content style=\"fixed-case\">TMJ<\/jats:styled-content>\n                    structures with release of cytokines,\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    s and other molecular markers that interact in a complex manner may be responsible for tissue degeneration in internal derangements. As internal derangements may be symptom\u2010free, the degree of inflammation, but also other mechanisms, may be important for pain development.\n                  <\/jats:p>","DOI":"10.1111\/joor.12480","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T02:12:44Z","timestamp":1483582364000},"page":"481-491","source":"Crossref","is-referenced-by-count":49,"title":["The role of molecular pain biomarkers in temporomandibular joint internal derangement"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-5439","authenticated-orcid":false,"given":"M.","family":"Ernberg","sequence":"first","affiliation":[{"name":"Section for Orofacial Pain and Jaw Function Department of Dental Medicine Karolinska Institutet Huddinge Sweden"},{"name":"The Scandinavian Center for Orofacial Neurosciences (SCON) Huddinge 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