Coe Marion A, Nuzzo Paul A, Lofwall Michelle R, Walsh Sharon L
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky; Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky.
Center on Drug and Alcohol Research, College of Medicine, University of Kentucky, Lexington, Kentucky.
J Pain. 2017 Jul;18(7):825-834. doi: 10.1016/j.jpain.2017.02.433. Epub 2017 Mar 6.
A common clinical problem with opioid analgesics is the loss of analgesic efficacy after repeated dosing; when this occurs, it is not clear what principles should guide providing effective analgesia among opioid-dependent individuals. This within-subject inpatient study aimed to determine if physically dependent opioid abusers (n = 11) experience changes in oxycodone-induced analgesia during 2 oxycodone maintenance (30 mg orally 4 times per day) phases: initial stabilization (days 1-3) and after 6 weeks of chronic dosing. Six sessions (3 each phase), measured threshold, tolerance, and pain ratings for a Pressure Pain Test and Cold Pressor Test after a single double-blind dose of oxycodone 30 mg (initial stabilization) and 0, 30, and 60 mg (chronic dosing) given in place of a scheduled maintenance dose. Physiologic and opioid agonist effects were assessed during chronic dosing sessions. There was no analgesic response to oxycodone 30 mg. Oxycodone (60 mg) produced a 25% increase in peak Cold Pressor Test threshold compared with placebo, and significantly increased expired breath CO2, miosis, and ratings of abuse liability measures. These data suggest that more than twice the acute oxycodone maintenance dose is needed to produce robust acute analgesia, although adverse effects (eg, respiratory depression and abuse signals) may occur with lower doses.
To understand sensitivity to opioid analgesia in opioid-dependent individuals, this article describes experimental pain, subjective and physiological responses during stabilization and after 6 weeks of oxycodone maintenance. Oxycodone produced euphoric effects and miosis with limited evidence of analgesia.
阿片类镇痛药常见的临床问题是重复给药后镇痛效果丧失；当出现这种情况时，尚不清楚在阿片类药物依赖个体中提供有效镇痛应遵循哪些原则。这项受试者自身的住院研究旨在确定身体依赖阿片类药物的滥用者（n = 11）在两个羟考酮维持阶段（每天口服30毫克，4次）：初始稳定期（第1 - 3天）和慢性给药6周后，羟考酮诱导的镇痛效果是否会发生变化。在单次双盲给予30毫克羟考酮（初始稳定期）以及在慢性给药阶段给予0、30和60毫克（代替预定维持剂量）后，进行六次测试（每个阶段各3次），测量压力疼痛测试和冷压测试的阈值、耐受性和疼痛评分。在慢性给药测试期间评估生理和阿片类激动剂效应。对30毫克羟考酮无镇痛反应。与安慰剂相比，60毫克羟考酮使冷压测试峰值阈值提高了25%，并显著增加了呼出的二氧化碳、瞳孔缩小以及滥用倾向指标评分。这些数据表明，需要超过急性羟考酮维持剂量两倍的剂量才能产生强大的急性镇痛效果，尽管较低剂量可能会出现不良反应（如呼吸抑制和滥用信号）。
为了解阿片类药物依赖个体对阿片类镇痛药的敏感性，本文描述了在稳定期以及羟考酮维持6周后实验性疼痛、主观和生理反应。羟考酮产生欣快感和瞳孔缩小，镇痛证据有限。
