ARRY-470 can significantly reduce bone cancer pain behaviors. Injection of green fluorescent protein (GFP)+ sarcoma cells into the intramedullary space of the femur results in significantly greater spontaneous flinching pain behaviors compared to sham injected mice from day 8 until day 20 post cell injection (A). Note that at day 14 there is a rapid escalation of pain behaviors, which is when invasion and growth of GFP+ cancer cells occurs within the periosteum. ARRY-470 therapy significantly reduces cancer pain behaviors if this therapy is administered before sprouting and neuroma formation occur, in either an early/acute (days 6-8), or an early/sustained (days 6-20) fashion (B). In contrast, ARRY-470 administered at late time points (days 18-20), when nerve sprouting and neuroma-like structures have already formed, did not significantly reduce cancer-related spontaneous guarding pain behaviors. Each point or bar represents the mean ± SEM. Brackets indicate the groups being compared. *p < 0.01.