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Research ArticleArticle

Prolonged Analgesic Effect of Ketamine, anN-Methyl-d-Aspartate Receptor Inhibitor, in Patients with Chronic Pain

Toril Rabben, Per Skjelbred and Ivar Øye
Journal of Pharmacology and Experimental Therapeutics May 1999, 289 (2) 1060-1066;
Toril Rabben
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Per Skjelbred
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Ivar Øye
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Abstract

We examined the role of N-methyl-d-aspartate (NMDA) receptors in chronic (pathological) pain in humans by using the NMDA receptor antagonist ketamine as a probe. Thirty patients with neuropathic pain in the trigeminal area were given an i.m. injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg. Pethidine 1.0 mg/kg served as a control. Three different response patterns were observed. Ketamine caused a long-term (6–24 h) analgesic effect partly dissociated from the mental side effects in 8 of the 26 patients who completed the study; these patients also had a slight analgesic effect of pethidine. In nine patients, ketamine caused a short-lasting (<2 h) analgesic effect closely associated with the mental side effects, whereas pethidine caused little or no analgesia. The remaining nine patients did not experience any reduction of pain after either drug in spite of characteristic side effects. One week after the i.m. challenge the patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules to be taken orally as a nightly dose for three consecutive nights. Five of the eight patients who had a long-term analgesic effect of the i.m. challenge reported decreased pain on days after ketamine. None of the others reported an analgesic effect. The phenomenon of long-term depression of pain in a subgroup of patients was thus confirmed when ketamine was given p.o. These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients. In others, pain appears to be mediated by NMDA receptor-independent mechanisms. We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states.

Footnotes

  • Send reprint requests to: Dr. Ivar Øye, Department of Pharmacology, P.O. Box 1057 Blindern, N-0316 Oslo, Norway. E-mail:ivar.oye{at}labmed.uio.no

  • Abbreviations:
    NMDA
    N-methyl-d-aspartate
    AMPA
    α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
    PCP
    phencyclidine
    VAS
    visual analog scale
    • Received July 29, 1998.
    • Accepted December 15, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 2
1 May 1999
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Research ArticleArticle

Prolonged Analgesic Effect of Ketamine, anN-Methyl-d-Aspartate Receptor Inhibitor, in Patients with Chronic Pain

Toril Rabben, Per Skjelbred and Ivar Øye
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1060-1066;

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Research ArticleArticle

Prolonged Analgesic Effect of Ketamine, anN-Methyl-d-Aspartate Receptor Inhibitor, in Patients with Chronic Pain

Toril Rabben, Per Skjelbred and Ivar Øye
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1060-1066;
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