Systemic treatment with the N-methyl-D-aspartate (NMDA) antagonist memantine (MEM) resulted in a decrease in mechanical hyperalgesia and mechanical allodynia in neuropathic rats. Bolus injections of 5, 10 and 20 mg/kg MEM (i.p.) attenuated withdrawal responses following mechanical stimulation for up to 6 h post-injection while saline had no effect. A more remarkable effect was observed following chronic treatment with MEM via mini-osmotic pumps (8 mg/kg per h for 7 days, i.p.), in which nociceptive responses were decreased during treatment and remained depressed for 3 days post-treatment. These antinociceptive effects can be obtained at doses which do not produce motor dysfunction. The results of this study demonstrate that MEM has a therapeutic effect on mechanical hyperalgesia and allodynia and may be considered as an alternative treatment for pathological pain in the clinical setting.