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Teaching Neurons to Respond to Placebos Could Help Treat Parkinson’s

Scientist have discovered a way to make neurons respond to a placebo (a medically ineffective treatment), in the same way as they would to medically effective treatment, according to a study published today in The Journal of Physiology.

They found that it is possible to turn a neuron which previously hasn’t responded to placebos (placebo ‘non-responder’ neuron) into a placebo ‘responder’ by conditioning Parkinson patients with apomorphine, a dopaminergic drug used in the treatment of Parkinson’s disease (PD).

When a placebo (saline solution) was given for the first time, it induced neither clinical benefit nor associated neuronal changes in the thalamus, a brain region known to be involved in PD. However, if repeated administrations of apomorphine were performed before placebo administration, a placebo was capable of increasing thalamus neuronal activity along with clinical improvement (reduction of muscle rigidity). Interestingly, the higher the previous administrations of apomorphine was, the larger the neuronal changes and the clinical improvement. When apomorphine was administered for 4 days in a row, the subsequent administration of a placebo induced a response that was as large as the one induced by apomorphine. These changes lasted for 24 hours.

The researchers administered apomorphine, either 1, 2, 3 or 4 days before the surgical implantation of electrodes for deep brain stimulation, which is an effective treatment for PD. During surgery, they replaced apomorphine with a placebo and recorded from single neurons in the thalamus along with the assessment of muscle rigidity of the arm.

Fabrizio Benedetti, from the Department of Neuroscience at University of Turin Medical School, Italy and first author of the study, explained,

Photo of placebo bottles.

Researchers found that it is possible to turn a neuron which previously hasn’t responded to placebos (placebo ‘non-responder’ neuron) into a placebo ‘responder’ by conditioning Parkinson patients with apomorphine, a dopaminergic drug used in the treatment of Parkinson’s disease (PD). Image is for illustrative purposes only. Credit: Elaine and Arthur Shapiro/NIH.

‘These findings show that is possible to teach neurons in the thalamus to respond to placebos, so that a placebo non-responder can be turned into a placebo responder. These findings may have profound implications and applications, because we can reduce drug intake by exploiting these learning mechanisms. Since this study shows that there is a memory for drug action, the alternate administration drug-placebo-drug- placebo etc. means people would need to take less medication but yet obtain the same clinical benefit.

‘If a placebo is given after four previous administrations of apomorphine, the placebo response can be as large as the drug response, and this effect lasts up to 24 hours. Therefore, a future challenge will be to see whether this effect can be extended beyond 24 hours.’

About this Parkinson’s disease research

Source: Helga Groll – The Physiological Society
Image Source: The image is credited to Elaine and Arthur Shapiro/NIH and is in the public domain.
Original Research: Abstract for “Teaching neurons to respond to placebos” by Fabrizio Benedetti, Elisa Frisaldi, Elisa Carlino, Lucia Giudetti, Alan Pampallona, Maurizio Zibetti, Michele Lanotte, and Leonardo Lopiano in Journal of Physiology. Published online February 9 2016 doi:10.1113/JP271322


Abstract

Teaching neurons to respond to placebos

Placebos have been found to affect the patient’s brain in a number of 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 the 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 1 through 4, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after 4 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 4 apomorphine administrations were again elicited after a re-exposure to a placebo 24 hr post-surgery, but not after 48 hr. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo nonresponders can be turned into responders, with important implications in the clinical setting.

“Teaching neurons to respond to placebos” by Fabrizio Benedetti, Elisa Frisaldi, Elisa Carlino, Lucia Giudetti, Alan Pampallona, Maurizio Zibetti, Michele Lanotte, and Leonardo Lopiano in Journal of Physiology. Published online February 9 2016 doi:10.1113/JP271322

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