NMDA receptor antagonists for the treatment of neuropathic pain.
OBJECTIVE
The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response (sensitivity) of individual neuropathic pain disorders to NMDA receptor antagonist therapy.


METHODS
PubMed (including MEDLINE), EMBASE and CENTRAL were searched up to October 26, 2009 for randomized placebo controlled trials (RCTs) on neuropathic pain. The methodological quality of the included trials was independently assessed by two authors using the Delphi list. Fixed or random effects model were used to calculate the summary effect size using Hedges' g.


METHODS
NA.


METHODS
The patients used for the study were neuropathic pain patients.


METHODS
The interventions used were NMDA receptor antagonists.


METHODS
The outcome of measurements was the reduction of spontaneous pain.


RESULTS
Twenty-eight studies were included, meeting the inclusion criteria. Summary effect sizes were calculated for subgroups of studies evaluating ketamine IV in complex regional pain syndrome (CRPS), oral memantine in postherptic neuralgia and, respectively, ketamine IV, and oral memantine in postamputation pain. Treatment with ketamine significantly reduced pain in postamputation pain (pooled summary effect size: -1.18 [confidence interval (CI) 95% -1.98, -0.37], P = 0.004). No significant effect on pain reduction could be established for ketamine IV in CRPS (-0.65 [CI 95% -1.47, 0.16], P = 0.11) oral memantine in postherptic neuralgia (0.03 [CI 95% -0.51, 0.56], P = 0.92) and for oral memantine in postamputation pain (0.38 [CI 95% -0.21, 0.98], P = 0.21).


CONCLUSIONS
Based on this systematic review, no conclusions can yet be made about the efficacy of NMDA receptor antagonists on neuropathic pain. Additional RCTs in homogenous groups of pain patients are needed to explore the therapeutic potential of NMDA receptor antagonists in neuropathic pain.
Department of Anesthesiology, VU University Medical Center, Amsterdam, the Netherlands. s.collins@vumc.nl
Susan
S
Collins
Marnix J
MJ
Sigtermans
Albert
A
Dahan
Wouter W A
WW
Zuurmond
Roberto S G M
RS
Perez
D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008559:Memantine / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D008559:Memantine