Quante Markus, Scharein Ekehard, Zimmermann Roger, Langer-Brauburger Birgit, Bromm Burkhard
Institute of Physiology, University Hospital Eppendorf, Hamburg, Germany.
Arzneimittelforschung. 2004;54(3):143-51. doi: 10.1055/s-0031-1296951.
The analgesic effects of morphine (CAS 57-27-2) in clinical use are well described. Sedation is discussed as a relevant side-effect, mostly based on data recorded in normal subjects without pain. The aim of this study was to quantify and to evaluate electrophysiologically the analgesic and sedative effects of morphine for the first time using an experimental pain model.
Analgesic and sedative effects of a low dose of morphine sulfate (CAS 6211-15-0; 10 mg i.v.) were determined using a standard phasic pain model (intracutaneously administered electrical pulses) in a placebo-controlled design with seven healthy subjects. Five blocks (1 block = 80 stimuli) of painful stimuli were applied, covering a period of 3 h. Analgesia was assessed by subjective pain ratings and by pain-related brain potentials. Sedation was determined by the power spectra of the spontaneous EEG, by auditory evoked potentials (AEP), reaction times and mood scales.
In all subjects the pain related variables were suppressed maximally 2 h after morphine administration (p < 0.01 versus placebo), indicated by a decrease of the pain ratings by about 45% and of the pain related brain potentials by about 50%. Interestingly, no effect on any sedation variable was found (p > 0.05).
The lack of sedative effects in the presence of marked analgesia was surprising in comparison with results of previous studies. It is concluded that the experimental pain increased the arousal level thus counteracting morphine-induced sedation. This may explain why other studies found relevant sedation after morphine application in the absence of pain. This underlines that sedative effects of analgesic drugs should be evaluated in the presence of pain. In relation to other analgesics (meperidine, pentacozine, nortilidine, flupirtine and tramadol) evaluated by exactly the same experimental protocol, morphine exhibited a potent analgesia with the smallest sedative effects of all.
吗啡（化学物质登记号57 - 27 - 2）在临床应用中的镇痛效果已有详尽描述。镇静作用作为一种相关副作用也被提及，不过大多是基于在无疼痛的正常受试者中记录的数据。本研究的目的是首次使用实验性疼痛模型，从电生理角度对吗啡的镇痛和镇静作用进行量化和评估。
采用标准的阶段性疼痛模型（皮内注射电脉冲），以安慰剂对照设计，对7名健康受试者测定低剂量硫酸吗啡（化学物质登记号6211 - 15 - 0；静脉注射10毫克）的镇痛和镇静作用。施加五组（1组 = 80次刺激）疼痛刺激，持续3小时。通过主观疼痛评分和与疼痛相关的脑电位评估镇痛效果。通过自发脑电图的功率谱、听觉诱发电位（AEP）、反应时间和情绪量表测定镇静作用。
在所有受试者中，吗啡给药后2小时疼痛相关变量受到最大程度抑制（与安慰剂相比，p < 0.01），表现为疼痛评分降低约45%，与疼痛相关的脑电位降低约50%。有趣的是，未发现对任何镇静变量有影响（p > 0.05）。
与先前研究结果相比，在明显镇痛的情况下缺乏镇静作用令人惊讶。得出的结论是，实验性疼痛提高了觉醒水平，从而抵消了吗啡诱导的镇静作用。这或许可以解释为什么其他研究发现在无疼痛情况下应用吗啡后会出现明显的镇静作用。这强调了应在有疼痛的情况下评估镇痛药的镇静作用。与通过完全相同实验方案评估的其他镇痛药（哌替啶、喷他佐辛、去甲替林、氟吡汀和曲马多）相比，吗啡显示出强效镇痛作用，且镇静作用最小。
