Icing is a widely used initial intervention for skeletal muscle injury in sports settings. However, accumulating evidence suggests that icing impairs muscle regeneration, potentially via delayed monocyte/macrophage accumulation. To elucidate the mechanisms underlying this icing-induced delay, we investigated whether icing modulates the monocyte chemoattractant protein 1 (MCP-1)/CC chemokine receptor 2 (CCR2) axis governing monocyte/macrophage recruitment. We comprehensively characterized inflammatory cell dynamics in a rodent crush-injury model using immunostaining and flow cytometry. During the very early phase (up to 5 h postinjury), neutrophils were the dominant inflammatory cell population within the lesion. Subsequently, MCP-1 concentrations and CCR2 + monocytes/macrophages increased and became prominent within 24 h, suggesting that MCP-1/CCR2 signaling prominently contributes to monocyte/macrophage recruitment during this early phase. Consistently, CD68 mid CD163 lo monocytes/macrophages, which exhibited the highest Ccr2 expression, predominated during the first 24 h. Immediate icing transiently suppressed MCP-1 production by neutrophils and monocytes/macrophages during this very early phase and was associated with attenuated subsequent recruitment of circulating monocytes. Consequently, monocyte/macrophage accumulation peaked at 48 h in the non-icing group but was delayed until 72 h in the immediate icing group. Notably, the late-icing model demonstrated that withholding icing during the early phase preserved normal monocyte/macrophage dynamics. Collectively, these results show that immediate icing disrupts the early MCP-1/CCR2-associated recruitment phase, likely by reducing the number of inflammatory cells and their production of MCP-1, thereby contributing to delayed monocyte/macrophage accumulation. These findings provide a crucial mechanistic basis for reconsidering and optimizing the timing of cryotherapy in clinical and sports settings.
Tamari et al. (Fri,) studied this question.