Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48207, USA.
Exp Clin Psychopharmacol. 2010 Jun;18(3):277-83. doi: 10.1037/a0018899.
Basal sleepiness-alertness modulates drug effects. Sleepiness produced by sleep restriction leads to increased nociceptive sensitivity, suggesting opioid analgesia may also be modulated by sleepiness-alertness. This study compared thermal nociceptive sensitivity in sleepy versus nonsleepy participants after codeine or placebo. Twelve healthy normal adults, 18 to 35 years of age, had an 8-hr nocturnal polysomnogram (NPSG) followed by a Multiple Sleep Latency Test (MSLT; Carskadon and Dement, 1987). All had sleep efficiencies > 80% on their NPSG; 6 had average MSLT >or= 8 min (nonsleepy group) and 6 had latencies < 8 min (sleepy group). Participants were assessed following 8-hr time-in-bed with standard MSLT, and nociceptive assessments (using a radiant heat stimulation method) were conducted the following day with codeine 30 mg b.i.d. (0900 and 1300) or placebo b.i.d. Finger withdrawal latency (FWL) in seconds was measured to 5 different heat intensities randomly presented to the index finger pad of each hand. Mean +/- 1 SD MSLT values in the sleepy group were 4.72 +/- 1.83 min and 13.04 +/- 4.90 min in the nonsleepy group. As hypothesized, increased FWL (decreased nociception) was observed with lower heat intensities, codeine, and in the nonsleepy group. More important, there was a Group x Drug interaction with codeine increasing FWL in the nonsleepy, but not the sleepy, group. These data show the analgesic effects of codeine are diminished in sleepy versus nonsleepy individuals. They suggest clinical differences in response to analgesics are partly explained by basal state of sleepiness-alertness.
基础睡眠-觉醒状态调节药物作用。睡眠限制引起的困倦会导致痛觉敏感性增加，这表明阿片类镇痛药的作用也可能受到睡眠-觉醒状态的调节。本研究比较了困倦和不困倦参与者在服用可待因或安慰剂后的热痛觉敏感性。12 名健康正常成年人，年龄 18-35 岁，进行了 8 小时夜间多导睡眠图（NPSG）和多次睡眠潜伏期试验（MSLT；Carskadon 和 Dement，1987）。所有参与者的 NPSG 睡眠效率均>80%；6 名参与者的平均 MSLT≥8 分钟（不困倦组），6 名参与者的潜伏期<8 分钟（困倦组）。参与者在 8 小时卧床后进行标准 MSLT 评估，次日在服用可待因 30mg bid（0900 和 1300）或安慰剂 bid 后进行痛觉评估（使用辐射热刺激法）。食指退缩潜伏期（FWL）以秒为单位测量，分别向每只手的食指垫随机呈现 5 种不同的热强度。困倦组的平均 MSLT 值为 4.72±1.83 分钟，不困倦组为 13.04±4.90 分钟。如假设的那样，随着热强度、可待因和不困倦组的降低，FWL（疼痛感觉降低）增加。更重要的是，存在一个组×药物的相互作用，可待因增加了不困倦组而不是困倦组的 FWL。这些数据表明，与不困倦的个体相比，可待因的镇痛作用在困倦的个体中减弱。它们表明，对镇痛药的反应的临床差异部分是由基础睡眠-觉醒状态解释的。
