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Papers of the Week


Papers: 27 Mar 2021 - 2 Apr 2021


Animal Studies


2021 Mar 26


Cancer Res

Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-induced Pain.

Authors

De Logu F, Marini M, Landini L, Souza Monteiro de Araujo D, Bartalucci N, Trevisan G, Bruno G, Marangoni M, Schmidt B L, Bunnett NW, Geppetti P, Nassini R
Cancer Res. 2021 Mar 26.
PMID: 33771895.

Abstract

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.