PT  - JOURNAL ARTICLE
AU  - Kufreobong E. Inyang
AU  - Christine M. Evans
AU  - Matthew Heussner
AU  - Margaret Petroff
AU  - Mark Reimers
AU  - Paola D. Vermeer
AU  - Nathan Tykocki
AU  - Joseph K. Folger
AU  - Geoffroy Laumet
TI  - Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain
AID  - 10.1101/2022.09.06.506411
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.06.506411
4099  - http://biorxiv.org/content/early/2022/09/08/2022.09.06.506411.short
4100  - http://biorxiv.org/content/early/2022/09/08/2022.09.06.506411.full
AB  - Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain, because of our lack of mechanistic understanding. Cancer-derived small extracellular vesicles (Cancer-sEVs) are well- positioned to function as mediators of communication between cancer cells and neurons. Inhibition of Cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified Cancer-sEVs is sufficient to induce pain hypersensitivity in naïve mice. Cancer-sEVs triggered calcium influx in nociceptors and inhibition or ablation of nociceptors protect against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human Cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by Cancer-sEVs was validated in our mouse model and its inhibition alleviated cancer pain in mice. These findings define a role of Cancer-sEVs in cancer pain and identify several druggable targets.Competing Interest StatementThe authors have declared no competing interest.