Department of Anaesthesiology, University Hospital Erlangen, Krankenhausstrasse 12, D-91054, Erlangen, Germany.
Br J Anaesth. 2010 Mar;104(3):359-68. doi: 10.1093/bja/aep372. Epub 2010 Jan 3.
Preclinical and clinical studies suggest an important role for cholinesterase inhibitors in pain therapy. The aim of this study was to examine the analgesic and antihyperalgesic properties of the cholinesterase inhibitor physostigmine and the opioid alfentanil, alone and in combination, in an experimental pain model in humans.
Twenty healthy volunteers were enrolled in this double-blind and placebo-controlled cross-over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities, measured on a numeric rating scale (NRS) from 0 to 10, and the extent of the hyperalgesic areas were assessed before, during, and 145 min after i.v. infusions of physostigmine (30 microg kg(-1) in 15 min), alfentanil (20 microg kg(-1) in 2 min), the combination of the same doses of both drugs, or saline 0.9%. The type of interaction was determined by fitting an interaction model to the data.
Starting from a baseline value of NRS=6, the maximum reduction of pain intensity was 50.4 (sd 22.3) % after alfentanil, 35.4 (20.0) % after physostigmine, and 60.4 (17.1) % after the combination. The hyperalgesic areas were reduced by 53.8 (33.2) %, 47.0 (26.3) %, and 54.8 (33.2) %, respectively. The data were best described by a model assuming an infra-additive interaction for analgesic and antihyperalgesic effects.
Physostigmine and alfentanil showed distinct effects on pain and hyperalgesia in a human pain model. The interaction of both drugs was found to be infra-additive.
临床前和临床研究表明，胆碱酯酶抑制剂在疼痛治疗中有重要作用。本研究旨在研究在人类实验性疼痛模型中，单独使用和联合使用胆碱酯酶抑制剂毒扁豆碱和阿芬太尼的镇痛和抗痛觉过敏作用。
本双盲安慰剂对照交叉研究纳入了 20 名健康志愿者。高电流密度经皮电刺激引起自发性急性疼痛和对机械性疼痛刺激（刺痛痛觉过敏）的稳定痛觉过敏区。使用数字评分量表（NRS）从 0 到 10 对疼痛强度进行评估，并在静脉输注毒扁豆碱（15 分钟内 30μg/kg）、阿芬太尼（2 分钟内 20μg/kg）、两种药物相同剂量的组合或生理盐水 0.9%前后及 145 分钟后评估痛觉过敏区的范围。通过拟合交互模型来确定交互作用的类型。
从 NRS=6 的基线值开始，阿芬太尼后疼痛强度最大降低 50.4（sd 22.3）%，毒扁豆碱后降低 35.4（20.0）%，联合用药后降低 60.4（17.1）%。痛觉过敏区分别减少 53.8（33.2）%、47.0（26.3）%和 54.8（33.2）%。数据最好通过假设镇痛和抗痛觉过敏作用呈次加性相互作用的模型来描述。
毒扁豆碱和阿芬太尼在人类疼痛模型中对疼痛和痛觉过敏均有明显作用。两种药物的相互作用被发现呈次加性。
