Hummel T, Kraetsch H G, Lötsch J, Hepper M, Liefhold J, Kobal G
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Chronobiol Int. 1995 Feb;12(1):62-72. doi: 10.3109/07420529509064501.
The aim of the study was to investigate the analgesic effects of two opioids [dihydrocodeine (DHC) and tramadol] when administered either in the morning or evening. The experimental technique used is based on chemosomatosensory event-related potentials (CSSERPs) in response to painful chemical stimuli that are applied to the nasal mucosa. Eighteen healthy volunteers participated in the experiments. The study followed a controlled, randomized, double-blind, sixfold, cross-over design. Thus, each of the three medications (90 mg DHC, 50 mg tramadol, or placebo) was perorally administered to all subjects on different days at 08:00 or 20:00 h. Measurements were performed before and 60, 120, 240, and 360 min after administration of the medication. In addition to the assessment of CSSERP, subjects rated the intensity of the stimuli. Moreover, unspecific drug effects were monitored by means of acoustical event-related potentials and the subjects' performance in a video game. The results indicated that the painful intensity of the chemical stimuli strongly increased during evening sessions. In addition, both DHC and tramadol exerted stronger analgesic effects when administered in the evening. Thus, an inflexible scheme of prescription might produce either an increase of pain in the morning due to insufficient analgesia or the unnecessary overdosing of analgesics in the evening.
该研究的目的是调查两种阿片类药物[二氢可待因（DHC）和曲马多]在早晨或晚上给药时的镇痛效果。所采用的实验技术基于对施加于鼻粘膜的疼痛化学刺激作出反应的化学体感事件相关电位（CSSERPs）。18名健康志愿者参与了实验。该研究采用了对照、随机、双盲、六重交叉设计。因此，三种药物（90毫克DHC、50毫克曲马多或安慰剂）中的每一种在不同日期的08:00或20:00时经口服给予所有受试者。在给药前以及给药后60、120、240和360分钟进行测量。除了评估CSSERP外，受试者还对刺激强度进行了评分。此外，通过听觉事件相关电位和受试者在电子游戏中的表现来监测非特异性药物作用。结果表明，在晚上的实验中，化学刺激的疼痛强度大幅增加。此外，DHC和曲马多在晚上给药时均发挥出更强的镇痛效果。因此，一成不变的处方方案可能会因镇痛不足导致早晨疼痛加剧，或者在晚上不必要地过量使用镇痛药。
