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Papers of the Week

Papers: 18 Mar 2023 - 24 Mar 2023

Basic Science

Animal Studies, Molecular/Cellular, Pharmacology/Drug Development

Cancer Pain, Musculoskeletal Pain

2023 Mar 18

Brain Behav Immun


Schwann Cell Insulin-like Growth Factor Receptor Type-1 Mediates Metastatic Bone Cancer Pain in Mice.


Landini L, Marini M, Souza Monteiro de Araujo D, Romitelli A, Montini M, Albanese V, Titiz M, Innocenti A, Bianchini F, Geppetti P, Nassini R, De Logu F


Insulin growth factor-1 (IGF-1), an osteoclast-dependent osteolysis biomarker, contributes to metastatic bone cancer pain (MBCP), but the underlying mechanism is poorly understood. In mice, the femur metastasis caused by intramammary inoculation of breast cancer cells resulted in IGF-1 increase in femur and sciatic nerve, and IGF-1-dependent stimulus/non-stimulus-evoked pain-like behaviors. Adeno-associated virus-based shRNA selective silencing of IGF-1 receptor (IGF-1R) in Schwann cells, but not in dorsal root ganglion (DRG) neurons, attenuated pain-like behaviors. Intraplantar IGF-1 evoked acute nociception and mechanical/cold allodynia, which were reduced by selective IGF-1R silencing in DRG neurons and Schwann cells, respectively. Schwann cell IGF-1R signaling promoted an endothelial nitric oxide synthase-mediated transient receptor potential ankyrin 1 (TRPA1) activation and release of reactive oxygen species that, via macrophage-colony stimulating factor-dependent endoneurial macrophage expansion, sustained pain-like behaviors. Osteoclast derived IGF-1 initiates a Schwann cell-dependent neuroinflammatory response that sustains a proalgesic pathway that provides new options for MBCP treatment.