Memantine (a N ‐methyl‐ d ‐aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double‐blinded, cross‐over study. (Danish Pain Research Center, University of Aarhus, Aarhus, Denmark) Anesth Analg 2000;91:960–966.

Evidence has accumulated that the N ‐methyl‐ d ‐aspartate receptor system plays a role in continuous and stimulus‐evoked pain after nerve injury. The analgesic effect of memantine on a group of patients with chronic pain after surgery was examined in this randomized, double‐blinded, study. Nineteen patients randomly received either memantine or placebo in the first 5‐week treatment period. A washout period of 4 weeks was followed by another 5‐week treatment period of 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, 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 completed the study. There was no difference between memantine and placebo on any of the outcome measures. Conclude that memantine at a dosage of 20 mg/d does not reduce spontaneous or evoked pain in patients with nerve injury pain. Comment by Tat‐Leang Lee, M.D. The treatment of patients suffering from chronic neuropathic pain remains a clinical challenge, particularly in cases where opioid therapy fails to provide sufficient pain relief. Experimental data concerning the role of NMDA‐mediated processes in central sensitization and the effects of NMDA receptor antagonists in different models of neuropathic pain have been well established. Currently, clinically available NMDA antagonists have narrow therapeutic windows and are limited by psychomimetic and other side effects. There exists a need to improve on this therapeutic ratio. Potential methods include the use of more selective NMDA antagonists that modulate binding sites within the NMDA complex, using novel routes including central axis delivery, or in combination with drugs. Combinations of opioids and NMDA antagonists may hold the most promise. Recently, a 1:1 mixture of morphine with dexmethorphan hydrobromide allowed satisfactory pain relief in chronic pain patients at a significantly lower morphine dose. 1 In this study, there were 3 patients who had morphine as part of their conventional treatment. Although specific data is not available, it would be interesting to know if memantine proved to be more effective in these patients.