College of Dentistry, Department of Orthodontics, University of Florida, Gainesville, FL, USA Department of Oral Surgery, University of Florida, Gainesville, FL, USA Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
Pain. 2012 Oct;153(10):2009-2016. doi: 10.1016/j.pain.2012.04.026. Epub 2012 Aug 4.
Analgesia is particularly susceptible to placebo responses. Recent studies in humans have provided important insights into the neurobiology underlying placebo-induced analgesia. However, human studies provide incomplete mechanistic explanations of placebo analgesia because of limited capacity to use cellular, molecular, and genetic manipulations. To address this shortcoming, this article describes the development of a rat model of conditioned analgesia in an operant pain assay. Specifically, rats were conditioned to associate a placebo manipulation with the analgesic effect of 1mg/kg morphine (subcutaneously) on facial thermal pain. We found that conditioned (placebo) responding bore 3 of the hallmarks of placebo-induced analgesia: (1) strong interanimal variability in the response, (2) suppression by the opiate antagonist naloxone (5mg/kg subcutaneously), and (3) a positive predictive relationship between the unconditioned analgesic effect and the conditioned (placebo) effect. Because of the operant nature of the assay and the use of only a mild noxious thermal stimulus, we suggest that these results provide evidence of placebo-induced analgesia in a preclinical model that utilizes an affective behavioral end point. This finding may provide opportunities for invasive preclinical studies allowing greater understanding of placebo-induced analgesia, thus paving the way for avenues to harness its benefits.
镇痛作用特别容易受到安慰剂效应的影响。最近的人类研究为理解安慰剂引起的镇痛作用的神经生物学机制提供了重要的见解。然而，由于细胞、分子和遗传操作的能力有限，人类研究提供的安慰剂镇痛作用的机制解释并不完整。为了解决这一不足，本文描述了在操作性疼痛测定中建立条件性镇痛的大鼠模型。具体来说，大鼠被训练将安慰剂操作与 1mg/kg 吗啡（皮下）对面部热痛的镇痛作用联系起来。我们发现，条件（安慰剂）反应具有安慰剂诱导镇痛的 3 个特征：（1）反应在动物间具有很强的变异性，（2）阿片拮抗剂纳洛酮（5mg/kg 皮下）抑制，（3）未条件作用的镇痛效应与条件（安慰剂）效应之间存在正相关关系。由于测定的操作性性质和仅使用轻度有害的热刺激，我们认为这些结果在使用情感行为终点的临床前模型中提供了安慰剂诱导镇痛的证据。这一发现可能为侵入性临床前研究提供机会，从而更好地理解安慰剂诱导的镇痛作用，为利用其益处铺平道路。
