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However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.<\/jats:p>","DOI":"10.1177\/154405910708600604","type":"journal-article","created":{"date-parts":[[2009,1,8]],"date-time":"2009-01-08T19:39:42Z","timestamp":1231443582000},"page":"491-505","source":"Crossref","is-referenced-by-count":63,"title":["Orofacial Pain in Cancer: Part I\u2014Mechanisms"],"prefix":"10.1177","volume":"86","author":[{"given":"R.","family":"Benoliel","sequence":"first","affiliation":[{"name":"Department of Oral Medicine, The Hebrew University, Hadassah Faculty of Dental Medicine, PO Box 12272, Jerusalem 91120, Israel;"},{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois-Chicago, USA;"},{"name":"Universities of Medicine and Dentistry of New Jersey, New Jersey Dental School, 110 Bergen Street, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, The Hebrew University, Hadassah Faculty of Dental Medicine, PO Box 12272, Jerusalem 91120, Israel;"},{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois-Chicago, USA;"},{"name":"Universities of Medicine and Dentistry of New Jersey, New Jersey Dental School, 110 Bergen Street, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Eliav","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, The Hebrew University, Hadassah Faculty of Dental Medicine, PO Box 12272, Jerusalem 91120, Israel;"},{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois-Chicago, USA;"},{"name":"Universities of Medicine and Dentistry of New Jersey, New Jersey Dental School, 110 Bergen Street, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Jurevic","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, The Hebrew University, Hadassah Faculty of Dental Medicine, PO Box 12272, Jerusalem 91120, Israel;"},{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois-Chicago, USA;"},{"name":"Universities of Medicine and Dentistry of New Jersey, New Jersey Dental School, 110 Bergen Street, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Elad","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, The Hebrew University, Hadassah Faculty of Dental Medicine, PO Box 12272, Jerusalem 91120, Israel;"},{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois-Chicago, USA;"},{"name":"Universities of Medicine and Dentistry of New Jersey, New Jersey Dental School, 110 Bergen Street, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2007,6,1]]},"reference":[{"key":"ABBADIE-ETAL-1996","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00343-H"},{"key":"AGGARWAL-ETAL-2002","doi-asserted-by":"publisher","DOI":"10.2174\/1568010023344571"},{"key":"AHMED-ETAL-2000","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.22.4.3795"},{"key":"ALANEN-ETAL-2000","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2000.00795.x"},{"key":"ALVARES-AND-FITZGERALD-1999","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00140-2"},{"key":"ANDERSON-ETAL-1998","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981001)83:7<1433::AID-CNCR22>3.0.CO;2-4"},{"key":"ANDREEV-ETAL-1995","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00024-M"},{"key":"ANDREWS-ETAL-1995","doi-asserted-by":"publisher","DOI":"10.1159\/000098746"},{"key":"APFEL-2001","doi-asserted-by":"crossref","unstructured":"Apfel SC (2001). 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