Evaluation of the analgesic efficacy of AZD1940, a novel cannabinoid agonist, on post-operative pain after lower third molar surgical removal
Evaluation of the analgesic efficacy of AZD1940, a novel cannabinoid agonist, on post-operative pain after lower third molar surgical removal
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DOI：
10.1016/j.sjpain.2012.08.004
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发表时间：
2013-01-01
影响因子：
1.6
通讯作者：
Quiding, Hans
中科院分区：
文献类型：
--
作者：
Kalliomaki, Jarkko;Segerdahl, Marta;Quiding, Hans
目的：评估AZD 1940，一种新型的外周作用大麻素CB 1/CB 2受体激动剂，在患者接受第三磨牙surgical removal.Methods：这是一项随机，双盲，安慰剂对照研究，患者计划手术切除的影响下第三磨牙。患者在手术前1.5小时接受800 μ g AZD 1940、500 mg萘普生或安慰剂的单次口服给药。根据一项人体单次给药研究的早期数据，选择了800 μ g AZD 1940的剂量，该研究将其确定为耐受性良好的最高剂量。术后0 - 8 h，采用视觉模拟量表（VAS，0- 100 mm）评估持续性术后疼痛（主要变量）和下颌运动疼痛，得出持续性疼痛曲线下面积（VAS AUC（0-8）（h））和下颌运动疼痛曲线下面积（VAS（JM）AUC（0-8 h））。记录至要求急救药物（对乙酰氨基酚）的时间。结果：共151例患者随机分为AZD 1940组（n = 61）、安慰剂组（n = 59）和萘普生组（n = 31）。AZD 1940与安慰剂之间的疼痛VAS AUC 0（-8 h）或VAS（JM）AUC（0-8 h）无统计学显著差异。与安慰剂相比，萘普生显著降低疼痛VAS AUC（0-8 h）和VAS（JM）AUC（0-8 h）（两者均p < 0.0001）。与安慰剂组相比，接受萘普生治疗的患者要求使用急救药物的人数显著减少，至急救的持续时间更长，而AZD 1940和安慰剂组在这些结局变量方面无显著差异。与安慰剂相比，AZD 1940给药后观察到VAMS项目“镇静”和“高”的统计学显著性增加。VAMS的增加在数值上与以前的研究结果相比，具有中枢作用的大麻素。AZD 1940治疗中最常见的不良事件（AE）为体位性头晕（80%的受试者）、恶心（26%）、低血压（21%）和头痛（13%），大多数AE为轻度至中度。结论：CB 1/CB 2受体激动剂AZD 1940在产生主观大麻素效应的剂量下，不能减轻下第三磨牙手术切除后的术后疼痛。外周CB 1/CB 2受体本身的激活对于治疗人类急性伤害性疼痛的临床相关性可能较小。（C）2012年斯堪的纳维亚疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Aim: To evaluate the analgesic efficacy of AZD1940, a novel peripherally acting cannabinoid CB1/CB2 receptor agonist, in patients undergoing third molar surgical removal.Methods: This was a randomized, double-blind, placebo-controlled study in patients scheduled for surgical removal of an impacted lower third molar. Patients received a single oral dose of 800 mu g AZD1940, 500mg naproxen or placebo 1.5 h before surgery. The dose of 800 mu g AZD1940 was selected based on earlier data from a single dose study in man, in which it was identified as the highest well tolerated dose. Ongoing post-operative pain (primary variable) and pain on jaw movement were assessed on a visual analog scale (VAS, 0-100mm) from 0 to 8 h postoperatively, deriving the area under the curve of ongoing pain (VAS AUC(0-8) (h)), and of pain on jaw movement (VAS(JM) AUC(0-8 h)). The time to requesting rescue medication (acetaminophen) was recorded. Subjective cannabinoid effects were assessed by the visual analog mood scale (VAMS).Results: In total, 151 patients were randomized to AZD1940 (n = 61), placebo (n = 59) or naproxen (n = 31). There was no statistically significant difference in pain VAS AUC0(-8 h) or in VAS(JM) AUC(0-8 h) between AZD1940 and placebo. Naproxen significantly reduced both pain VAS AUC(0-8 h) and VAS(JM) AUC(0-8 h) as compared with placebo (p < 0.0001 for both). Significantly fewer patients on naproxen requested rescue medication and the duration of time to rescue was greater, as compared with placebo, whereas there were no significant differences between AZD1940 and placebo in these outcome variables. Statistically significant increases in VAMS items "sedated" and "high" were observed after AZD1940 compared with placebo. The increases in VAMS were numerically small compared with previous findings with a centrally acting cannabinoid. The most commonly observed adverse events (AE) on treatment with AZD1940 were postural dizziness (80% of subjects), nausea (26%), hypotension (21%) and headache (13%), most AE being mild to moderate.Conclusion: The CB1/CB2 receptor agonist AZD1940 did not reduce post-operative pain after lower third molar surgical removal at doses exerting subjective cannabinoid effects.Implications: Activation of peripheral CB1/CB2 receptors per se is probably of less clinical relevance for the treatment of acute nociceptive pain in man. (C) 2012 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.