Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine
Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine
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DOI：
10.1016/j.pain.2006.06.028
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发表时间：
2006-12-15
期刊：
影响因子：
7.4
通讯作者：
Richarz, Ute
中科院分区：
文献类型：
--
作者：
Koltzenburg, Martin;Pokorny, Rolf;Richarz, Ute
这是第一个随机对照试验，测试经皮递送阿片类药物在健康志愿者中的镇痛效果，并评估不同实验性疼痛测试在这种情况下检测镇痛的敏感性。在双盲、随机、安慰剂对照的三种急性疼痛实验模型（热痛、疼痛电刺激、冷加压）中，比较了完全激动剂芬太尼（TDF：12.5或25 μ g/h）和部分激动剂丁丙诺啡（TDB：35 μ g/h）的经皮应用。4-20名健康受试者（15名男性，5名女性）的交叉研究。贴剂给药72小时，并在基线和24和72小时测量疼痛水平，洗脱期为11天。冷加压试验对镇痛效果最敏感，在24 It时，所有活性化合物的疼痛强度曲线下面积显著减少（平均减少：14%TDF 12.5 μ g/h 35%TDF 25 μ g/h 43%TDB 35 μ g/h）。TDF 25 μ g/h和TDB 35 μ g/h的热痛阈值显著增加。疼痛性电刺激未能表现出镇痛作用。冷加压模型中的镇痛幅度与TDF剂量相关，完全激动剂芬太尼和部分激动剂丁丙诺啡的效果相当。我们的结论是冷加压试验是最敏感的镇痛效果在健康受试者和12.5 μ g/h芬太尼的经皮剂量达到显着的疼痛减轻与安慰剂相比。受试者发生阿片类典型AE，包括头晕、恶心和呕吐。未发生严重AE。(c)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
This is the first randomized controlled trial that tests the analgesic efficacy of transdermally delivered opioids in healthy volunteers and that assesses the sensitivity of different experimental pain tests to detect analgesia in this setting. Transdermal application of the full agonist fentanyl (TDF: 12.5 or 25 mu g/h) and the partial agonist buprenorphine (TDB: 35 mu g/h) was compared in three experimental models of acute pain (heat pain, painful electrical stimulation, cold pressor) in a double-blind, randomized, placebo-controlled. 4-arm crossover study with 20 healthy subjects (15 men, 5 women). Patches were administered for 72 h and pain levels measured at baseline and 24 and 72 h, with an 11-day wash-out. The cold pressor test was most sensitive to analgesic effects, with significant reductions in area under the pain intensity curve for all active compounds at 24 It (average reductions: 14% TDF 12.5 mu g/h 35% TDF 25 mu g/h 43% TDB 35 mu g/h). There were significant increases in heat pain threshold for TDF 25 mu g/h and TDB 35 mu g/h. Painful electrical stimulation failed to demonstrate an analgesic effect. The magnitude of analgesia in the cold pressor model showed some correlation with TDF dosage and comparable effects for the full agonist fentanyl and the partial agonist buprenorphine. We conclude that the cold pressor test was most sensitive to analgesic effects in healthy subjects and that a transdermal dose of 12.5 mu g/h fentanyl achieved significant pain reduction compared with placebo. Subjects experienced opioid-typical AEs including dizziness, nausea and vomiting. No serious AEs occurred. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.