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Current treatments are somewhat effective but have severe side effects. For the future development of safer CIBP treatments, in this study, we sought to investigate the mechanisms whereby the nerve-cancer interaction controls CIBP. We found that c-Kit, a receptor tyrosine kinase, was activated in the dorsal root ganglia (DRG) sensory neurons of mice with CIBP and that c-Kit\u2019s sole ligand, stem cell factor (SCF), was enhanced in the bone marrow with bone metastasis. When DRGs were treated with SCF or conditioned medium from high SCF-expressing cancer cells, in vitro nerve sprouting was enhanced, and this effect was abolished with c-Kit inhibitors. Mice inoculated intrafemorally with cancer cells that had varying levels of SCF expression developed CIBP and enhanced peripheral nerve sprouting in an SCF-dependent manner. Downstream proteomic analysis revealed that SCF upregulated and activated fibroblast growth factor 1 (FGF1) in DRGs. When FGF1 was knocked down in DRGs, SCF-mediated nerve sprouting was prevented. 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