Data from: NMDA receptor antagonists and pain relief: a meta-analysis of experimental trials

OBJECTIVES: We conducted a meta-analysis of controlled trials that used
experimental models of acute pain and hyperalgesia to examine the
analgesic effects of N-methyl-D-aspartate receptor (NMDAR) antagonists.
METHODS: Six major databases were systematically searched (to 03/2018) for
studies using human evoked pain models to compare NMDAR antagonists with
no-intervention controls. Pain outcome data were analyzed with
random-effects meta-analysis. RESULTS: Searches identified 70 eligible
trials (N=1069). Meta-analysis found that low-dose ketamine (<1
mg/kg) produced a decrease in the size of hyperalgesic area (Standardized
Mean Difference=0.54, CI95[0.34, 0.74], p<.001), and a 1.2-point
decrease (CI95[0.88, 1.44], p<.001) in pain ratings from 4.6 to 3.4
on a 0-10 scale (a 26% reduction). Similar analgesia was observed for
acute and hyperalgesic models and was constant across the dosing range
(0.03-1.00 mg/kg). Moderate-high variability in effect size was observed
and mild side effects (e.g. sedation, sensory disturbance) were common. No
effects of dextromethorphan were found. CONCLUSIONS: Findings provide
robust evidence for analgesic and anti-hyperalgesic effects of ketamine,
supporting its utility for acute and chronic pain management. However,
pain relief was modest, suggesting ketamine may potentially be most useful
when opioids are contraindicated, rapid analgesia is required or for pain
resistant to conventional medication.

目的：我们对采用急性疼痛和痛觉过敏实验模型的对照试验开展了荟萃分析，旨在探究N-甲基-D-天冬氨酸受体（N-methyl-D-aspartate receptor，NMDAR）拮抗剂的镇痛效应。
方法：系统检索了6个主要数据库（截至2018年3月）中使用人类诱发痛模型比较NMDAR拮抗剂与无干预对照的研究。采用随机效应荟萃分析对疼痛结局数据进行分析。
结果：检索共识别出70项符合条件的试验（样本量N=1069）。荟萃分析显示，低剂量氯胺酮（<1 mg/kg）可减小痛觉过敏区域的面积（标准化均数差（Standardized Mean Difference）=0.54，95%置信区间（CI95）[0.34, 0.74]，p<0.001），并使0-10分制的疼痛评分从4.6分降低1.2分（CI95[0.88,1.44]，p<0.001），降幅达26%。在急性疼痛和痛觉过敏模型中观察到相似的镇痛效果，且在0.03-1.00 mg/kg的剂量范围内效果稳定。效应量存在中高度变异，轻度副作用（如镇静、感觉障碍）较为常见。未观察到右美沙芬的效应。
结论：研究结果为氯胺酮的镇痛和抗痛觉过敏效应提供了强有力的证据，支持其在急性和慢性疼痛管理中的应用价值。然而，其疼痛缓解效果温和，提示氯胺酮可能在阿片类药物禁忌、需要快速镇痛或常规药物难治性疼痛的情况下最为有用。