Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo.
Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo.
复制标题
静脉输注 NMDA 拮抗剂氯胺酮治疗伴有异常性疼痛的慢性创伤后疼痛：与阿芬太尼和安慰剂的双盲比较。
作者：
M. Max;M. Byas;R. Gracely;G. Bennett
NMDA拮抗剂和阿片类药物可减轻动物和人类实验产生的痛觉过敏，可能是通过减弱中枢神经系统对传入输入的高度反应。一些对患者的小型研究表明，静脉注射或快速输注n -甲基- d -天冬氨酸（NMDA）拮抗剂氯胺酮可以缓解一些神经性疼痛，但也会产生认知和情绪障碍。在一项随机、双盲、交叉试验中，我们通过2小时静脉输注NMDA拮抗剂氯胺酮（平均剂量，58 mg）、阿片受体激动剂阿芬太尼（平均剂量，11 mg）和安慰剂治疗8例慢性创伤后疼痛和广泛的机械异常性疼痛患者。之所以选择这些患者，是因为广泛的感觉测试表明，中枢处理过程的改变导致了他们的症状。选择慢速输注药物，以观察疼痛缓解是否先于剂量限制性副作用。在2小时输注期间达到的峰值效应评分的平均值为疼痛缓解：氯胺酮，65%，阿芬太尼，46%，安慰剂，22%（与安慰剂相比，氯胺酮p < 0.01，阿芬太尼p = 0.08）；对于缓解异位性疼痛：氯胺酮71%，阿芬太尼57%，安慰剂21%（氯胺酮和阿芬太尼p < 0.01）。只有在出现令人不快的药物副作用后，才会出现明显的症状缓解。停止输注后，在副作用消失前疼痛消失。我们得出结论，NMDA拮抗剂可能有希望治疗神经性疼痛，但需要策略来提高其治疗比例，如鞘内给药或更选择性药物的全身治疗。
NMDA antagonists and opioids relieve experimentally produced hyperalgesia in animals and humans, presumably by attenuating a heightened central 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 neuropathic 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 with 2-h intravenous infusions of the NMDA antagonist ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 mg), 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 relief would precede dose-limiting side effects. Means of the peak effect scores achieved during the 2-h infusion were for pain relief: ketamine, 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 developed 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 treatment of neuropathic pain, but strategies are needed to improve their therapeutic ratio, such as intrathecal administration or systemic treatment with more selective drugs.