Lacosamide was tested in the streptozotocin rat model of diabetic neuropathic pain in comparison to drugs which are commonly used in the treatment of diabetic neuropathic pain, i.e. antidepressants and anticonvulsants. In diabetic rats, lacosamide attenuated cold (10, 30 mg/kg, i.p.), warm (3, 10, 30 mg/kg, i.p.) and mechanical allodynia (30 mg/kg, i.p.). Streptozotocin-induced thermal and mechanical hyperalgesia were reduced by lacosamide at doses of 10 and 30 mg/kg, i.p. Morphine (3 mg/kg) showed similar efficacy on allodynia and hyperalgesia. Amitriptyline (10 mg/kg), venlafaxine (15 mg/kg), levetiracetam (180 mg/kg) and pregabalin (100 mg/kg) exhibited significant effects on thermal allodynia and mechanical hyperalgesia. Only treatment with amitriptyline (30 mg/kg, i.p.) produced full reversal of thermal allodynia comparable to lacosamide. Lamotrigine (45 mg/kg, i.p.) had no effect on both behavioral readouts. Lacosamide's potency and efficacy in reversing pain behavior might be due to its new, yet unknown mechanism of action.