Fig. 4

Anticoagulants, but not antiplatelet agents, cancel the preventive effect of TMα against oxaliplatin (OHP)-induced neuropathic allodynia in mice. a Drug administration schedule. TMα at 10 mg/kg was administered i.p. 0.5 h before i.p. OHP at 5 mg/kg (b–g). b Effect of argatroban (AT), a parenteral direct thrombin inhibitor, on the anti-neuropathic effect of TMα. AT at 10 mg/kg was administered i.p. 1 h before OHP treatment. c Effect of warfarin (War), a vitamin K antagonist, on the anti-neuropathic effect of TMα. War at 1 mg/kg was administered orally 48 h, 24 h, and 1 h before OHP treatment, three times in total. d Effect of dabigatran (Dabi), an oral direct thrombin inhibitor, on the anti-neuropathic effect of TMα. Dabi at 75 mg/kg was administered orally 1 h before OHP treatment. e, f Effect of rivaroxaban (Riva), an oral direct Xa inhibitor, on the anti-neuropathic effect of TMα. Riva at 10 mg/kg was administered orally once 1 h before OHP treatment (e) and repeatedly 48 h, 24 h, and 1 h before OHP treatment, three times in total (f). g Lack of effect of aspirin (ASA) and clopidogrel (Clo), antiplatelet agents, on the anti-neuropathic effect of TMα. ASA at 50 mg/kg or Clo at 10 mg/kg was administered orally once 1 h before OHP treatment. h Effects of War and Riva on the prothrombin time. Blood samples were collected 1 h after three repeated administrations of War and after single or three repeated administrations of Riva, as mentioned above (a). V, vehicle. Data show the mean with SEM for five mice. *P < 0.05, **P < 0.01 vs. vehicle + vehicle in vehicle-treated mice; ^†P < 0.05, ^††P < 0.01 vs. vehicle + vehicle in OHP-treated mice; ^#P < 0.05, ^##P < 0.01 vs. vehicle + TMα in OHP-treated mice