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

Francesco de Logu, Matilde Marini, Lorenzo Landini, Daniel Souza Monteiro de Araujo, Niccolo Bartalucci, Gabriela Trevisan, Gennaro Bruno, Martina Marangoni, Brian Schmidt, Nigel W. Bunnett, Pierangelo Geppetti, Romina Nassini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3387-3401
Number of pages15
JournalCancer Research
Volume81
Issue number12
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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