The μ-opioid agonist remifentanil attenuates hyperalgesia evoked by blunt and punctuated stimuli with different potency:: a pharmacological evaluation of the freeze lesion in humans
The μ-opioid agonist remifentanil attenuates hyperalgesia evoked by blunt and punctuated stimuli with different potency:: a pharmacological evaluation of the freeze lesion in humans
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DOI：
10.1016/s0304-3959(02)00349-4
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发表时间：
2003-03-01
期刊：
影响因子：
7.4
通讯作者：
Angst, MS
中科院分区：
文献类型：
--
作者：
Lötsch, J;Angst, MS
诱发痛觉过敏的实验性疼痛模型，即对临床疼痛中经常存在的伤害性刺激的敏感性增加，是研究抗伤害性药物概况的重要工具。正确解释这些模型中得到的结果需要对它们的机理进行理解。本研究评估了冷冻损伤，一种痛觉过敏的实验模型，在人类。12名健康受试者在冷冻皮肤之前和之后，以及在计算机控制的μ阿片受体激动剂瑞芬太尼的输注期间，在两阶段，单次，随机和双盲研究设计中，用机械（刷，间断和钝）和电（5，250和2000 Hz正弦波电流）刺激进行测试，靶向0和6 ng/ml之间的五种不同血浆浓度。药效学建模技术被用来描述冷冻和给药对机械和电痛阈的影响。冷冻皮肤导致钝性和间断性刺激的痛觉过敏，并分别降低了29%和73%的痛阈。未检测到对刷牙或电刺激的痛觉过敏。瑞芬太尼减弱钝性刺激的痛觉过敏的效力约为间断性刺激的痛觉过敏的两倍，如瑞芬太尼血浆浓度与钝性刺激的痛阈增加之间的显著陡峭的线性关系所示。瑞芬太尼减弱电疼痛，对低频刺激具有更大的效力。瑞芬太尼的效力差异表明不同的神经元机制介导钝性和间断性刺激的痛觉过敏。刷诱发和电痛觉过敏的情况下是兼容的观点，即机械痛觉过敏钝和间断刺激的冻结病变主要是由外周机制引起的。(C)2002年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Experimental pain models inducing hyperalgesia, i.e. an increased sensitivity to noxious stimuli often present in clinical pain, are important tools for studying antinociceptive drug profiles. The correct interpretation of results obtained in these models necessitates their mechanistic understanding. This study evaluated the freeze lesion, an experimental model of hyperalgesia, in humans. Twelve healthy subjects were tested with mechanical (brush, punctuated and blunt) and electrical (5, 250, and 2000 Hz sine wave current) stimuli before and after freezing the skin, and during a computer-controlled infusion of the mu-opioid agonist remifentanil targeting five different plasma concentrations between 0 and 6 ng/ml in a two-staged, single occasion, randomized, and double blind study design. Pharmacodynamic modeling techniques were used to describe the effect of freezing and drug administration on the mechanical and electrical pain thresholds. Freezing the skin resulted in hyperalgesia to blunt and punctuated stimuli and lowered the respective pain threshold by 29 and 73%. Hyperalgesia to brushing or electrical stimuli was not detected. Remifentanil attenuated hyperalgesia to blunt stimuli about twice as potently as hyperalgesia to punctuated stimuli, as indicated by a significantly steeper linear relationship between the remifentanil plasma concentration and the increase of the pain threshold to blunt stimuli. Remifentanil attenuated electrical pain with greater potency for low frequency stimulation. The potency difference of remifentanil suggests that different neuronal mechanisms mediate hyperalgesia to blunt and punctuated stimulation. Absence of brush-evoked and electrical hyperalgesia is compatible with the view that mechanical hyperalgesia to blunt and punctuated stimulation of the freeze lesion is predominantly caused by a peripheral mechanism. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.