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• W3136278209 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. SIGNIFICANCE: Schwann cell TRPA1 sustains cancer pain through release of M-CSF and oxidative stress, which promote the expansion and the proalgesic actions of intraneural macrophages. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3387/F1.large.jpg." @default.
• W3136278209 created "2021-03-29" @default.
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• W3136278209 date "2021-03-26" @default.
• W3136278209 modified "2023-10-18" @default.
• W3136278209 title "Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-Induced Pain" @default.
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• W3136278209 doi "https://doi.org/10.1158/0008-5472.can-20-3326" @default.
• W3136278209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8260461" @default.
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