Here, we show that, in contrast to the critical role of macrophage-derived HMGB1 in the CIPN caused by paclitaxel [6], oxaliplatin-induced peripheral neuropathy involves HMGB1, but is largely independent of macrophages, and that the TM/thrombin system restrains CIPN most probably by inactivating HMGB1 in the bloodstream. This evidence concerns the gene HMGB1 and peripheral neuropathy.