Placebo analgesia and beyond: a melting pot of concepts and ideas for neuroscience.

PURPOSE OF REVIEW In the last two decades, some of the neuroanatomical and neurophysiological substrates of the placebo effect have been elucidated. What has emerged is the multifactorial nature of the placebo effect, such that there is not a single placebo effect but many. Here we report on recent advances in our understanding of this phenomenon, with particular emphasis on its use as an experimental model to better clarify different brain mechanisms. RECENT FINDINGS One of the most interesting findings in the past few years is that the placebo effect is a learning phenomenon, which is powerfully influenced by the manipulation of different variables. The involvement of opioid mechanisms is supported by several studies on pain, but also by the exploration of new fields such as memory and cognition. Nonopioid mechanisms have been described as well, for example, in pain, Parkinson's disease and anxiety. Recent evidence confirms and extends previous findings on the key role of prefrontal regions in the placebo response. SUMMARY The study of the placebo effect is paying dividends and bodes well for the future. Whereas in clinical practice it can increase the efficacy of a therapy, in the experimental setting it represents an excellent tool for neuroscience.