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Received Oct 13, 2017; Accepted Dec 20, 2017
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1. Introduction
Placebo and nocebo effects are prevalent topics in current research, especially in the domain of pain, where they can be investigated comparatively easily and serve as a model for other systems (e.g., immune, motor, and respiratory systems [1]). While placebo hypoalgesia refers to decreased pain sensitivity due to an inert treatment (e.g., sham procedure and inert substance), its counterpart nocebo hyperalgesia is defined as increased pain sensitivity attributable to an inert treatment [2]. Due to their capacity to improve or worsen symptoms and well-being, placebo and nocebo effects are highly relevant not only in research but also in clinical practice. They contribute to most therapeutic effects [3], occur regularly in doctor-patient interactions [4], and are assumed to play a role in the development and maintenance of chronic pain and other diseases [5, 6]. Placebo and nocebo effects also significantly influence the outcome of randomized placebo-controlled clinical trials, for example, leading to an underestimation of clinical effects of novel drugs [7–9]. Although this clinical relevance and research on placebo and nocebo effects have prospered during the past decade, many issues remain unresolved or poorly understood. One of these issues that deserve our attention concerns the causing mechanisms of placebo and nocebo effects and the significance of conditioning in this realm. Only if we understand how these effects emerge, we can systematically take advantage of placebo and avoid nocebo effects, especially in the clinical context.
After giving a brief overview over current evidence and models on the development of placebo hypoalgesia and nocebo hyperalgesia including conditioning and expectation approaches, we will turn to studies that stress the significance of conditioning and demonstrate that conditioning effects might have been misunderstood and/or underestimated. We will highlight the need to better understand conditioned placebo and nocebo effects and propose experimental designs that allow a conclusive investigation of the specific mechanisms at work.
2. Development of Placebo and Nocebo Effects
Placebo and nocebo effects can be induced by different means. Empirical evidence shows that verbal suggestion [10], classical conditioning [11–13], and...