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Analgesic effects of excitatory amino acid (e.g. glutamate) modulation
 Using the rat formalin test as a clinically relevant pain model, we evaluated the effects of the glutamate NMDA (N-Methyl-D-Aspartate) receptor antagonist, ketamine, on pain-induced spinal sensitization and demonstrated that ketamine produced naloxone-insensitive preemptive analgesia but not suppression of formalin-induced spinal Fos immunoreactivity (Gilron et. al., 1999). With this and many other experimental studies suggesting a role for glutamate modulation in clinical pain, we conducted a randomized controlled trial of a glutamate antagonist at AMPA (2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid) and kainate receptors, LY293558 (Lilly Laboratories Inc.), in acute pain following oral surgery (Gilron, Max et. al., 2000). This trial demonstrated that LY293558 was well tolerated and selectively reduced movement-evoked versus spontaneous postoperative pain.
In the setting of chronic neuropathic pain, we conducted two randomized controlled trials of glutamate NMDA antagonists and one trial of the anticonvulsant topiramate (which has an AMPA/kainate receptor blocking effect):
a) In a trial of the NMDA antagonist, dextromethorphan, in facial neuralgias (Gilron, Booher et. al., 2000), we implemented new pain measurement scales and diagnostic stratifications for trials in facial neuralgias and described the lack of efficacy of dextromethorphan in this population.
b) In a comparative trial of two NMDA antagonists, dextromethorphan and memantine, in painful diabetic neuropathy and postherpetic neuralgia (Sang et. al., 2002), we reported selective efficacy of dextromethorphan in diabetic neuropathy, but not in postherpetic neuralgia, whereas memantine was ineffective in either condition.
c) We also completed a placebo-controlled, multiple crossover pilot study showing the first evidence of efficacy of topiramate in trigeminal neuralgia (Gilron, Booher et. al., 2001).
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Analgesic effects of excitatory amino acid (e.g. glutamate) modulation