NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation.
A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.
Gustin
S M
SM
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Germany Ospedale San Camillo, Instituto di Ricovero e Cura a Carattere Scientifico, Venezia, Italy Traumatology Hospital of the University of Tübingen, Germany Department of Clinical and Cognitive Neuroscience, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany Functional Imaging, Institute for Diagnostic Radiology and Neuroradiology, University of Greifswald, Germany.
Schwarz
A
A
Birbaumer
N
N
Sines
N
N
Schmidt
A C
AC
Veit
R
R
Larbig
W
W
Flor
H
H
Lotze
M
M
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement; D012019:Reflex Sympathetic Dystrophy / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors
D000700:Analgesics; D009020:Morphine; D010100:Oxygen; D008559:Memantine