Tröster Andreas, Sittl Ruth, Singler Boris, Schmelz Martin, Schüttler Jürgen, Koppert Wolfgang
Department of Anesthesiology, University Hospital Erlangen, Erlangen, Germany.
Anesthesiology. 2006 Nov;105(5):1016-23. doi: 10.1097/00000542-200611000-00024.
Numerous experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. It is suggested that spinal cyclooxygenase activity may contribute to the development and expression of opioid tolerance. The aim of the investigation was to determine analgesic and antihyperalgesic properties of the cyclooxygenase-2 inhibitor parecoxib on remifentanil-induced hypersensitivity in humans.
Fifteen healthy male volunteers were enrolled in this randomized, double-blind, placebo-controlled study in a crossover design. Transcutaneous electrical stimulation at high current densities was used to induce spontaneous acute pain (numeric rating scale 6 of 10) and stable areas of pinprick hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during, and after a 30-min intravenous infusion of remifentanil (0.1 microg x kg x min) or placebo (saline). Parecoxib (40 mg) was administered intravenously either with onset of electrical stimulation (preventive) or in parallel to the remifentanil infusion.
Remifentanil reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level. Preventive administration of parecoxib led to an amplification of remifentanil-induced antinociceptive effects during the infusion (71.3 +/- 7 vs. 46.4 +/- 17% of control) and significantly diminished the hyperalgesic response after withdrawal. In contrast, parallel administration of parecoxib did not show any modulatory effects on remifentanil-induced hyperalgesia.
The results confirm clinically relevant interaction of mu opioids and prostaglandins in humans. Adequate timing seems to be of particular importance for the antihyperalgesic effect of cyclooxygenase-2 inhibitors.
大量实验和临床研究表明，短期使用阿片类药物可增强疼痛敏感性。有研究表明，脊髓环氧化酶活性可能与阿片类药物耐受性的形成和表现有关。本研究旨在确定环氧化酶 -2 抑制剂帕瑞昔布对瑞芬太尼引起的人体超敏反应的镇痛和抗痛觉过敏特性。
15 名健康男性志愿者参与了这项随机、双盲、安慰剂对照的交叉设计研究。采用高电流密度的经皮电刺激来诱发自发性急性疼痛（数字评分量表为 10 分中的 6 分）和稳定的针刺痛觉过敏区域。在静脉输注瑞芬太尼（0.1μg·kg·min）或安慰剂（生理盐水）30 分钟之前、期间和之后，评估疼痛强度和痛觉过敏区域。帕瑞昔布（40mg）在电刺激开始时（预防性）或与瑞芬太尼输注同时静脉给药。
瑞芬太尼在输注期间减轻了疼痛和机械性痛觉过敏，但停药后，疼痛和痛觉过敏显著高于对照水平。预防性给予帕瑞昔布导致输注期间瑞芬太尼诱导的抗伤害感受作用增强（对照的 71.3±7% 对 46.4±17%），并显著减轻了停药后的痛觉过敏反应。相比之下，同时给予帕瑞昔布对瑞芬太尼诱导的痛觉过敏没有任何调节作用。
结果证实了μ阿片类药物与前列腺素在人体中具有临床相关的相互作用。适当的给药时机似乎对环氧化酶 -2 抑制剂的抗痛觉过敏作用尤为重要。
