Decoding Cold Mechanisms of Enhanced Bone Repair through Sensory Receptors and Molecular Pathways

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with physiological responses analyzed. Vasoconstriction was mediated by an increase in TRP channels, TRPA1 (p=0.012) and TRPM8 (p<0.001), within cortical defects enhancing sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and VEGF expression (p < 0.001), promoting angiogenesis vital for bone regeneration. Increased expression of osteogenic proteins PGC-1α (p = 0.039) and RBM3 (p<0.008) suggests stimulated reparative processes. Enhanced osteoblast differentiation and ALP presence at days 5 (three-fold, p=0.014) and 10 (two-fold, p=0.010) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.010) indicating presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy's multifaceted effects on bone repair, offering insights for therapeutic strategies.