{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:16:06Z","timestamp":1792264566304,"version":"4.4.0"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"860","funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030892"],"award-info":[{"award-number":["R01DE030892"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["F31DE034633-02"],"award-info":[{"award-number":["F31DE034633-02"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,7,29]]},"abstract":"<jats:p>\n                    Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, with patients frequently reporting spontaneous, neuropathic-like pain. Sympathetic and sensory nerves have been individually implicated in cancer progression, but whether and how these systems interact to drive pain and tumor growth have remained unclear. Here, we integrated prospective human data with reverse-translational mouse models to reveal that cancer-induced nerve injury unveils cross-talk between sympathetic postganglionic neurons and trigeminal sensory afferents in the tumor microenvironment. In patients, circulating norepinephrine (NE) correlated with spontaneous pain and perineural invasion, identifying a potential sympathetic contribution to disease burden. In mice, aggressive nonimmunogenic OSCC tumors evoked spontaneous nociceptive behaviors, elevated tumoral NE, and sensory nerve injury marked by ATF3 expression and hyperexcitability. Tumor-associated sensory neurons acquired adrenergic sensitivity through \u03b11-adrenergic receptor plasticity, whereas sympathetic neurons exhibited plasticity characterized by sprouting, altered gene expression, and heightened excitability, creating a maladaptive feed-forward loop that amplified nociceptive signaling. Disrupting this sympathetic-sensory communication by sympathectomy or selective ablation of TRPV1\n                    <jats:sup>+<\/jats:sup>\n                    sensory fibers reduced tumor growth, sympathetic tone, and spontaneous pain-like behaviors, although sensory adrenergic sensitivity persisted. Together, these findings establish that reciprocal sympathetic-sensory plasticity and cross-talk in the tumor may fuel both OSCC progression and neuropathic-like pain. Targeting this peripheral neuroplasticity may offer a translational strategy to limit tumor growth and alleviate pain.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aec3196","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:00:21Z","timestamp":1785348021000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Cancer-induced nerve injury unveils a sympathetic-to-sensory nerve axis in a mouse model of head and neck squamous cell carcinoma"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4147-8891","authenticated-orcid":true,"given":"Andre A.","family":"Martel Matos","sequence":"first","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-1316","authenticated-orcid":true,"given":"Lisa A.","family":"McIlvried","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5369-0063","authenticated-orcid":true,"given":"Nicole L.","family":"Horan","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9580-6784","authenticated-orcid":true,"given":"Jared I.","family":"Rothberg","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-4131","authenticated-orcid":true,"given":"Megan A.","family":"Atherton","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen V.","family":"Glass","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-668X","authenticated-orcid":true,"given":"Marci L.","family":"Nilsen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA."},{"name":"Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-4990","authenticated-orcid":true,"given":"Nicole N.","family":"Scheff","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA."},{"name":"Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002655"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104712"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202200019"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05374-w"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-10028-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-017-4800-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24396"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2015.03.006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anorl.2020.03.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2010.02.017"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202515"},{"key":"e_1_3_2_13_2","first-page":"290","article-title":"Case series: Cancer-related facial pain treated with stellate ganglion block","volume":"1","author":"Darabad R. 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