TY - JOUR
T1 - Peripheral nerve resident macrophages and schwann cells mediate cancer-induced pain A C
AU - de Logu, Francesco
AU - Marini, Matilde
AU - Landini, Lorenzo
AU - de Araujo, Daniel Souza Monteiro
AU - Bartalucci, Niccolo
AU - Trevisan, Gabriela
AU - Bruno, Gennaro
AU - Marangoni, Martina
AU - Schmidt, Brian
AU - Bunnett, Nigel W.
AU - Geppetti, Pierangelo
AU - Nassini, Romina
N1 - Funding Information:
We thank D. Preti (University of Ferrara, Ferrara, Italy) for providing A967079. This work was supported by European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 835286; to P. Geppetti), Associazione Italiana per la Ricerca sul Cancro (AIRC, IG2016-ID19247 and IG2020-ID24503) and Fondazione Cassa di Risparmio di Firenze, Italy (to R. Nassini), NIH (NS102722, DE026806, DK118971, DE029951 to N.W. Bunnett and B.L. Schmidt), and Department of Defense (W81XWH1810431 to N.W. Bunnett and B.L. Schmidt).
Funding Information:
N.W. Bunnett reports grants from NIH and Department of Defense during the conduct of the study, nonfinancial support from Endosome Therapeutics Inc. outside the submitted work, and is a founding scientist of Endosome Therapeutics Inc. P. Geppetti reports grants and personal fees from Eli-Lilly, TEVA, Novartis, Allergan/ AbbVie, and grants from Lundbeck outside the submitted work and is a founding scientist of FloNext Srl. R. Nassini is a founding scientist of FloNext Srl. No disclosures were reported by the other authors.
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/6
Y1 - 2021/6
N2 - Although macrophages (M≉) 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 M≉s (rM≉) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. M≉-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rM≉ 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 rM≉ expansion and pain-like behaviors. Depletion of rM≉s in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rM≉, oxidative stress, and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain.
AB - Although macrophages (M≉) 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 M≉s (rM≉) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. M≉-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rM≉ 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 rM≉ expansion and pain-like behaviors. Depletion of rM≉s in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rM≉, oxidative stress, and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain.
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U2 - 10.1158/0008-5472.CAN-20-3326
DO - 10.1158/0008-5472.CAN-20-3326
M3 - Article
AN - SCOPUS:85107984618
VL - 81
SP - 3387
EP - 3401
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 12
ER -