The Journal of Physiology, 2016; pp 1-14


Fabrizio Benedetti1,2, Elisa Frisaldi1, Elisa Carlino1, Lucia Giudetti3, Alan Pampallona3, Maurizio Zibetti1, Michele Lanotte1, Leonardo Lopiano1
1 University of Turin Medical School, Neuroscience Department, Turin, Italy
2 Plateau Rosa Labs, Breuil-Cervinia, Italy, Zermatt, Switzerland
3 Giancarlo Quarta Foundation, Milan, Italy

Placebos have been found to affect the patient’s brain in several conditions, such as pain and motor disorders. For example, in Parkinson’s disease, a placebo treatment induces a release of dopamine in the striatum and changes the activity of neurons in both thalamic and subthalamic nuclei. The present study shows that placebo administration for the first time induces neither clinical nor neuronal improvement in Parkinson patients who undergo implantation of electrodes for deep brain stimulation. However, this lack of placebo responsiveness can be turned into substantial placebo responses following previous exposure to repeated administrations of the anti-Parkinson agent apomorphine. As the number of apomorphine administrations increased from one to four, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after four apomorphine exposures, placebo administration induced clinical responses that were as large as those to apomorphine, along with long-lasting neuronal changes. These clinical placebo responses following four apomorphine administrations were again elicited after a re-exposure to a placebo 24 h after surgery, but not after 48 h. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo non-responders can be turned into responders, with important implications in the clinical setting.

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