胰岛素生长因子-1（IGF-1）是一种骨吸收生物标志物，其依赖于破骨细胞，并且对转移性骨癌疼痛（MBCP）有贡献，但其潜在机制尚不清楚。在小鼠中，通过乳腺癌细胞的内乳腺接种导致的股骨转移导致股骨和坐骨神经中IGF-1的增加，且产生IGF-1依赖的诱发/非诱发疼痛类似行为。基于腺相关病毒的shRNA选择性沉默IGF-1受体（IGF-1R）在施万细胞中，但不是在背根节神经元中，减轻了疼痛类似行为。足底注射IGF-1引发急性疼痛和机械/冷痛觉异常，这些异常分别由背根节神经元和施万细胞中选择性IGF-1R沉默所减轻。施万细胞IGF-1R信号促进了内皮型一氧化氮合酶介导的瞬时受体电压门控蛋白1（TRPA1）激活，并释放活性氧物质，通过巨噬细胞-集落刺激因子依赖的内皮丛组织巨噬细胞扩张，维持了疼痛类似行为。破骨细胞来源的IGF-1启动了一种施万细胞依赖的神经炎症反应，维持了一条促痛通路，为MBCP治疗提供了新选择。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。

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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.