TY - JOUR TI - Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-induced Pain AU - Logu, Francesco De AU - Marini, Matilde AU - Landini, Lorenzo AU - Araujo, Daniel Souza Monteiro de AU - Bartalucci, Niccolò AU - Trevisan, Gabriela AU - Bruno, Gennaro AU - Marangoni, Martina AU - Schmidt, Brian Lee AU - Bunnett, Nigel W. AU - Geppetti, Pierangelo AU - Nassini, Romina T2 - Cancer Research AB - Although macrophages (MΦ) are known to play a central role in neuropathic pain, their contribution to cancer pain has not been established. Here we report that depletion of sciatic nerve resident MΦs (rMΦ) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. MΦ-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rMΦ expansion, transient receptor potential ankyrin 1 (TRPA1) activation, and oxidative stress. Targeted deletion of Trpa1 revealed a key role for Schwann cell TRPA1 in sciatic nerve rMΦ expansion and pain-like behaviors. Depletion of rMΦs in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rMΦ, oxidative stress and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain. DA - 2021/01/01/ PY - 2021 DO - 10.1158/0008-5472.CAN-20-3326 DP - cancerres.aacrjournals.org J2 - Cancer Res LA - en SN - 0008-5472, 1538-7445 UR - https://cancerres.aacrjournals.org/content/early/2021/03/26/0008-5472.CAN-20-3326 Y2 - 2021/03/29/18:07:30 ER -