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Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-\u03b1, IL-1\u03b2, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28\u2009d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1\u03b2 and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory\/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.<\/jats:p>","DOI":"10.1177\/00220345211039482","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T10:19:25Z","timestamp":1633083565000},"page":"339-347","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Occlusal Trauma Induces Neuroimmune Crosstalk for a Pain State"],"prefix":"10.1177","volume":"101","author":[{"given":"H.B.","family":"Abdalla","sequence":"first","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.H.","family":"Napimoga","sequence":"additional","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.A.","family":"Trindade-da-Silva","sequence":"additional","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.C.V.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas\u2013UNICAMP, Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.A.","family":"Buarque e Silva","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas\u2013UNICAMP, Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Andrade e Silva","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas\u2013UNICAMP, Piracicaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.T.","family":"Clemente-Napimoga","sequence":"additional","affiliation":[{"name":"Faculdade S\u00e3o Leopoldo Mandic, Instituto e Centro de Pesquisas S\u00e3o Leopoldo Mandic, Laboratoy of Neuroimmune Interface of Pain Research, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,10]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-018-2639-z"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jopr.13235"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.10.059"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2008.09.012"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.12554"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2021.105115"},{"issue":"1","key":"e_1_3_3_8_1","first-page":"50","article-title":"Experimental occlusal interference induces the expression of protein gene products and substance P in masseter muscles of rats","volume":"42","author":"Cao Y","year":"2010","unstructured":"Cao Y, Li K, Fu KY, Xie QF. 2010. 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