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PAIN MEDICINE

A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-D-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain

Katja Wiech, PhD^1,*, Ralph-Thomas Kiefer, MD^1,, Stephanie Töpfner, MD, Hubert Preissl, PhD^*, Christoph Braun, PhD^*, Klaus Unertl, MD, Herta Flor, PhD, and Niels Birbaumer, PhD^*,

*Institute of Medical Psychology and Behavioral Neurobiology and the Department of Anesthesiology and Intensive Care Medicine, University of Tübingen, Tübingen, Germany, the Department of Neuropsychology, University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany, and the Center for Cognitive Neuroscience, University of Trento, Trento, Italy

Adress correspondence and reprint requests to R.-T. Kiefer, MD, Center for Medical Research, Department of Anesthesiology and Intensive Care Medicine, University of Tuebingen, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Address e-mail to thomas.kiefer{at}uni-tuebingen.de

In the present study we investigated the effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.

IMPLICATIONS: NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization.

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