Benedetti F, Amanzio M
Department of Neuroscience, University of Torino Medical School, Italy.
Prog Neurobiol. 1997 Jun;52(2):109-25. doi: 10.1016/s0301-0082(97)00006-3.
Placebo is a widespread phenomenon in medicine and biology and its mechanisms are understood only partially. Most of our understanding of placebo comes from studies on pain. In particular, placebo analgesia represents a situation where the administration of a substance known to be non-analgesic produces an analgesic response when the subject is told that it is a pain killer. Several theories try to explain this effect by means of anxiety mechanisms, cognitive processes and classical conditioning. However, the placebo response is bidirectional, i.e. analgesic and algesic. In fact, if a subject is told that the ineffective substance is a hyperalgesic drug, a pain increase may occur. The negative effects of placebo are called nocebo and, in extreme cases, they lead to severe pathological conditions. The neurobiology of placebo was born when some authors discovered that placebo analgesia is mediated by endogenous opioids. This claim comes from the observation that the opioid antagonist naloxone can reverse placebo analgesia. On the basis of the discovery of the anti-opioid action of the neuropeptide cholecystokinin, recent studies demonstrate that the blockade of cholecystokinin receptors potentiates the placebo analgesic response, thus suggesting an inhibitory role of cholecystokinin in placebo analgesia. Thus, by antagonizing the anti-opioid action of cholecystokinin during a placebo procedure, a potentiation of the endogenous opioid systems can be obtained.
安慰剂是医学和生物学中一种普遍存在的现象，其机制仅得到部分理解。我们对安慰剂的大多数认识来自于对疼痛的研究。特别是，安慰剂镇痛是指当告知受试者某种已知无镇痛作用的物质是止痛药时，该物质的给药会产生镇痛反应的情况。有几种理论试图通过焦虑机制、认知过程和经典条件作用来解释这种效应。然而，安慰剂反应是双向的，即镇痛和致痛。事实上，如果告知受试者该无效物质是一种致痛药物，可能会出现疼痛加剧的情况。安慰剂的负面影响被称为反安慰剂效应，在极端情况下，会导致严重的病理状况。当一些作者发现安慰剂镇痛是由内源性阿片类物质介导时，安慰剂神经生物学应运而生。这一观点源于阿片类拮抗剂纳洛酮可以逆转安慰剂镇痛的观察结果。基于神经肽胆囊收缩素的抗阿片作用的发现，最近的研究表明，阻断胆囊收缩素受体可增强安慰剂镇痛反应，从而提示胆囊收缩素在安慰剂镇痛中起抑制作用。因此，在安慰剂过程中通过拮抗胆囊收缩素的抗阿片作用，可以增强内源性阿片系统的作用。
