{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:16:09Z","timestamp":1792264569535,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Radiology Ultrasound"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Radiation\u2010induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF\u2010\u03b1) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation\u2010induced mucositis (RIM) and radiation\u2010associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF\u2010\u03b1 signaling in mice that underwent lingual irradiation to induce severe acute oral RIM\/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross\u2010sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real\u2010time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF\u2010\u03b1, its receptor, nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF\u2010\u03b1, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM\/RAP, it did inhibit the upregulation of TNF\u2010\u03b1\u2019s receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF\u2010\u03b1 signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.<\/jats:p>","DOI":"10.1111\/vru.12943","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T22:28:53Z","timestamp":1608676133000},"page":"255-263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early radiation\u2010induced oral pain signaling responses are reduced with pentoxifylline treatment"],"prefix":"10.1111","volume":"62","author":[{"given":"Mikayla L.","family":"Price","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences North Carolina State University  Raleigh North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Hao (Erik)","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences North Carolina State University  Raleigh North Carolina"},{"name":"Comparative Medicine Institute North Carolina State University  Raleigh North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Marcus","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences North Carolina State University  Raleigh North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Robertson","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine North Carolina State University  Raleigh North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-9009","authenticated-orcid":false,"given":"B. 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