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.

Peripheral nerve resident macrophages and schwann cells mediate cancer-induced pain A C / de Logu F.; Marini M.; Landini L.; de Araujo D.S.M.; Bartalucci N.; Trevisan G.; Bruno G.; Marangoni M.; Schmidt B.L.; Bunnett N.W.; Geppetti P.; Nassini R.. - In: CANCER RESEARCH. - ISSN 0008-5472. - ELETTRONICO. - 81:(2021), pp. 3387-3401. [10.1158/0008-5472.CAN-20-3326]

Peripheral nerve resident macrophages and schwann cells mediate cancer-induced pain A C

de Logu F.;Marini M.;Landini L.;Bartalucci N.;Trevisan G.;Bruno G.;Marangoni M.;Geppetti P.;Nassini R.
2021

Abstract

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.
2021
81
3387
3401
de Logu F.; Marini M.; Landini L.; de Araujo D.S.M.; Bartalucci N.; Trevisan G.; Bruno G.; Marangoni M.; Schmidt B.L.; Bunnett N.W.; Geppetti P.; Nassini R.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1261589
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