Table.

Preclinical Models of HNC-Associated Pain.

Model	Cell Line	Injection Site	Species	Pain Phenotypes	Behavioral Assessment Tool Used	References
Xenograft	Oral SCC (SCC-158)	Gingiva	Rats	Mechanical allodynia and thermal hyperalgesia in the whisker pad and submandibular skin	von Frey; hot plate	Hironaka et al. (2014); Nagamine et al. (2006)
	Oral SCC (SCC-158)	Hind paw	Rats	Paw mechanical allodynia; paw thermal hyperalgesia; spontaneous pain	Dynamic plantar; aesthesiometer; Hargreaves test; paw flinching, licking, lifting	Shinoda et al. (2008)
	Oral SCC (HSC-2)	Tongue	Mice	Oral function impairment; mechanical hypersensitivity in the whisker pad; spontaneous pain	Food intake; von Frey; conditioned place preference	Chodroff et al. (2016)
	Oral SCC (HSC-2)	Paw	Mice	No pain	Feeding; von Frey; conditioned place preference	Chodroff et al. (2016)
	Oral SCC (HSC-3)	Tongue	Mice	Facial allodynia; oral function impairment; thermal hyperalgesia; widespread pain; spontaneous pain	von Frey; dolognawmeter; Hargreaves test; tail pinch; conditioned place preference	Tu, Jensen, et al. (2021); Ye et al. (2017); Scheff et al. (2019); Scheff et al. (2018)
	Oral SCC (HSC-3)	Hind paw	Mice	Mechanical allodynia; thermal hyperalgesia	von Frey; dynamic plantar aesthesiometer; Hargreaves test	Tu, Jensen, et al. (2021); Ye et al. (2011); Ye, Ono, et al. (2014)
	Oral SCC (HSC-3)	Sciatic nerve	Mice	Mechanical allodynia; spontaneous pain; motor defects	von Frey; conditioned place preference; paw licking, shaking; toe-spreading	Salvo et al. (2020)
Allograft	HPV 16+ mouse oropharyngeal SCC	Hind paw	Mice	Paw mechanical allodynia; spontaneous pain	von Frey; Mouse Grimace Scale	Heussner et al. (2021)
Supernatant	Oral SCC (HSC-3, SCC-9, SCC-4)	Tongue	Mice	Oral function impairment	Dolognawmeter	Lam et al. (2015); Scheff et al. (2019); Scheff et al. (2018); Scheff et al. (2017); Scheff et al. (2020)
	Oral SCC (HSC-3, HSC-2, SCC-9)	Hind paw	Mice	Paw mechanical allodynia; paw thermal hyperalgesia; spontaneous pain	von Frey; Hargreaves test; conditioned place preference	Ruparel et al. (2015); Scheff et al. (2020); Lam et al. (2015)
	Cancer-conditioned rat Schwann cells (RSC-96)	Hind paw	Mice	Paw mechanical allodynia	von Frey	Salvo et al. (2019)
	Cancer-conditioned human Schwann cells	Hind paw	Mice	Paw mechanical allodynia	von Frey	Salvo et al. (2021)
Chemical induced	—	—	Mice	Oral function impairment; spontaneous pain	Dolognaweter; conditioned place preference	Tu, Jensen, et al. (2021); Scheff et al. (2018); Scheff et al. (2017)
Naturally occurring	—	—	Cats	Mechanical allodynia in the face; referred mechanical allodynia in the cornea; widespread pain	A pet owner administered quality-of-life questionnaire and visual assessment scoring tool; a clinician assessment questionnaire; electronic von Frey testing; Cochet-Bonnet aesthesiometry	Lai et al. (2021)

HNC, head and neck cancer; HPV, human papillomavirus; SCC, squamous cell carcinoma.