Considering our findings that a long-term inhibition of thrombin or its generation caused neuropathic allodynia together with the elevation in plasma HMGB1 levels after treatment with a subeffective dose of oxaliplatin, we assume that the endogenous TM/thrombin system restrains the development of oxaliplatin-induced peripheral neuropathy by degrading HMGB1 released from unknown cells in response to oxaliplatin. The gene discussed is HMGB1; the disease is peripheral neuropathy.