Evidence has accumulated that the N:-methyl-D-aspartate receptor system plays a role in continuous and particularly, in stimulus-evoked pain after nerve injury. We examined, in a randomized, double-blinded, cross-over fashion, the analgesic effect of memantine (a N:-methyl-D-aspartate receptor antagonist) in a group of patients with chronic pain after surgery. We randomized 19 patients to receive either memantine or placebo in the first 5-wk treatment period. A washout period of 4 wks was followed by another 5-wk treatment period with the opposite drug. The dosage of drug was increased from 5 to 20 mg/d. Pain was recorded daily, with the use of a 0-10 numeric rating scale. Before and at the end of each treatment period, pain and sensitivity were also assessed by using the McGill Pain Questionnaire, allodynia to touch, brush and cold, wind-up-like pain, and thresholds to mechanical stimuli (pressure and von Frey hair). A total of 15 patients (12 amputees and three patients with other nerve injuries) completed the study. There was no difference between memantine and placebo on any of the outcome measures. We conclude that memantine at a dosage of 20 mg/d does not reduce spontaneous or evoked pain in patients with nerve injury pain.
Implications: In a randomized, double-blinded and cross-over study, the analgesic effect of memantine (a drug which reduces the excitability of sensitized neurons in the dorsal horn) was examined in 19 patients with chronic pain after nerve injury.