Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation.
The role of central N-methyl-D-aspartate (NMDA) receptors in the pathogenesis of central pain was examined in nine patients with central dysesthesia pain after spinal cord injury. The central pain syndrome included spontaneous continuous and intermittent pain as well as evoked pain. Pain was evoked by non-noxious stimulation of the skin (allodynia) and by repeated pricking of the skin (wind-up-like pain). The severity of continuous and evoked pain was examined before and after the intravenous infusion of either the NMDA receptor antagonist ketamine (6 micrograms/kg/min after a bolus dose of 60 micrograms/kg), the mu-opioid receptor agonist alfentanil (0.6 microgram/kg/min after after a bolus dose of 7 micrograms/kg), or placebo (0.9% NaCl). A randomized, double-blind, crossover study design was used. It was found that both continuous and evoked pain were markedly reduced by the blockade of NMDA receptors by ketamine as well as by the activation of mu-opioid receptors by alfentanil. Neither ketamine nor alfentanil significantly changed thresholds for the sensation of heat pain. The reduction of pain was not associated with severe side effects; the most severe side effect of ketamine was bothersome dizziness in one patient, and only modest side effects were caused by alfentanil. The present data provide clinical evidence that the development of central dysesthesia pain after traumatic spinal cord injury is dependent on the activation of central NMDA receptors. The results further indicate that mu-opioid receptors are involved in the control of this type of pain.
Eide
P K
PK
Department of Neurosurgery, Ullevål Hospital, Oslo, Norway.
Stubhaug
A
A
Stenehjem
A E
AE
D000328:Adult; D000368:Aged; D015760:Alfentanil / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010292:Paresthesia / Q000188:drug therapy / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000294:innervation; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology*
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D015760:Alfentanil; D007649:Ketamine