| First Author | De Logu F | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 12 | Pages | 3387-3401 |
| PubMed ID | 33771895 | Mgi Jnum | J:316010 |
| Mgi Id | MGI:6719160 | Doi | 10.1158/0008-5472.CAN-20-3326 |
| Citation | De Logu F, et al. (2021) Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-Induced Pain. Cancer Res 81(12):3387-3401 |
| abstractText | Although macrophages (MPhi) 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 MPhis (rMPhi) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. MPhi-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rMPhi 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 rMPhi expansion and pain-like behaviors. Depletion of rMPhis in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rMPhi, 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. |
