Portenoy Russell K, Foley Kathleen M, Inturrisi Charles E
Pain Service, Dept. of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NYU.S.A. Cornell University Medical College, New York, NYU.S.A.
Pain. 1990 Dec;43(3):273-286. doi: 10.1016/0304-3959(90)90025-9.
In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain, e.g., neuropathic pains, may be unresponsive to these drugs. This concept has important implications for both clinical practice and basic understanding of opioid mechanisms. We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation. The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone. From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of 'complete' or 'adequate' analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs. Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects.
近年来，有观察发现患者对阿片类药物的反应可能会受到疼痛或疼痛综合征固有特性（如病理生理学）的影响，这一观察已发展为一种观点，即某些类型的疼痛，如神经性疼痛，可能对这些药物无反应。这一概念对临床实践和阿片类药物作用机制的基础理解都具有重要意义。我们对阿片类药物反应性进行了批判性评估，特别是与神经性疼痛相关的反应性，并提出了一个与临床相关的定义及其研究范式。通过对28例神经性疼痛患者阿片类药物输注的镇痛反应，以及对其中1例中枢性疼痛对氢吗啡酮输注迅速产生反应的患者的药代动力学和药效学关系的详细阐述，对该范式进行了说明。通过这一分析，我们假设：（1）人类的阿片类药物反应性可通过剂量递增至出现无法耐受的副作用或达到“完全”或“充分”镇痛时所实现的镇痛程度来定义；（2）阿片类药物反应性是一个连续体，而非一种质反应现象；（3）阿片类药物反应性由多种患者特征、疼痛相关因素以及药物选择性效应决定；（4）神经性机制可能会降低阿片类药物反应性，但不会导致对这些药物产生固有抗性。鉴于导致阿片类药物反应性的因素复杂，且观察到结果无法可靠预测，不应基于疼痛机制或任何其他因素会排除良好反应的假设而停用阿片类药物。阿片类药物的临床应用以及研究阿片类药物反应性的范式都应包括将剂量递增至最大耐受水平，并反复监测镇痛效果及其他效应。
