INTRAVENOUS-INFUSION OF THE NMDA ANTAGONIST, KETAMINE, IN CHRONIC POSTTRAUMATIC PAIN WITH ALLODYNIA - A DOUBLE-BLIND COMPARISON TO ALFENTANIL AND PLACEBO

NMDA antagonists and opioids relieve experimentally produced hyperalge sia in animals and humans, presumably by attenuating a heightened cent ral nervous system response to afferent input, A few small studies in patients have suggested that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA) antagonist ketamine relieve some neur opathic pains but also produce disturbances of cognition and mood, In a randomized, double-blind, crossover trial, we treated eight patients with chronic posttraumatic pain and widespread mechanical allodynia w ith 2-h intravenous infusions of the NMDA antagonist ketamine (mean do se, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 m g), and placebo. The patients were selected because extensive sensory testing suggested that altered central processing contributed to their symptoms. The slow rate of drug infusion was chosen to see if pain re lief would precede dose-limiting side effects. Means of the peak effec t scores achieved during the 2-h infusion were for pain relief: ketami ne, 65%, alfentanil, 46%, and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil, 57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil). Appreciable symptomatic relief deve loped only after the onset of unpleasant drug side effects. After the infusion was stopped, pain relief disappeared before the side effects resolved, We conclude that NMDA antagonists may have promise for the t reatment of neuropathic pain, but strategies are needed to improve the ir therapeutic ratio, such as intrathecal administration or systemic t reatment with more selective drugs.