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Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co\u2010opt different components of the neurotrophin pathway in metastasis, PNI, and pain.<\/jats:p>","DOI":"10.1002\/adbi.202200190","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T11:30:12Z","timestamp":1659612612000},"source":"Crossref","is-referenced-by-count":25,"title":["Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer"],"prefix":"10.1002","volume":"6","author":[{"given":"Coleen","family":"Doan","sequence":"first","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery Loma Linda University School of Dentistry  Loma Linda CA 92350 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley E.","family":"Aouizerat","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery New York University College of Dentistry  New York NY 10010 USA"},{"name":"Bluestone 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