Collectively, we propose that HMGB1, derived from non-macrophage cells, mediates oxaliplatin-induced peripheral neuropathy possibly through activation of TLR4, RAGE, and CXCL12/CXCR4 signaling, which is limited by the endogenous TM/thrombin system and attenuated by exogenously applied TMα in a thrombin-dependent manner (Fig. 6). This evidence concerns the gene HMGB1 and peripheral neuropathy.