Fig. 5

Long-term inhibition of enzymatic activity or generation of thrombin develops mechanical allodynia and elevates plasma HMGB1 levels in mice treated with oxaliplatin (OHP) at a subeffective dose. a, b Argatroban (AT), a parenteral direct thrombin inhibitor, at 10 mg/kg was administered i.p. 0.5 h before and once a day for 6 days after i.p. OHP at 1 mg/kg, a subeffective dose. c, d Warfarin (War), a vitamin K antagonist, at 1 mg/kg was administered orally 48 h, 24 h, and 0.5 h before and once a day for 6 days after treatment with the subeffective dose of OHP. e, f Rivaroxaban (Riva), an oral direct Xa inhibitor, at 10 mg/kg was administered orally 0.5 h before and once a day for 6 days after treatment with the subeffective dose of OHP. Nociceptive threshold was determined before and after OHP treatment (a, c, e), and blood samples for ELISA assay of plasma HMGB1 levels were obtained on day 7 after OHP treatment (b, d, f). V, vehicle. Data show the mean with SEM for six to eight (a) or five to eight (b) mice. *P < 0.05, **P < 0.01 vs. vehicle + vehicle