Scientists study misleading impact in nausea therapy at the molecular level

Overview

• Post By : Kumar Jeetendra


• Source: Ludwig Maximilian University of Munich


• Date: 28 Sep,2020

The molecular bases of the placebo effect are poorly understood. A team headed by Ludwig-Maximilians-Universitaet (LMU) in Munich researcher Karin Meissner has now studied the phenomenon in the context of nausea, and identified specific proteins that correlate with its positive impact.

The placebo effect seems to work wonders. In certain cases, administration of a’drug’ to patients who are unaware of the fact that the preparation contains no active agent can have a positive influence on their illness – relieving pain, as an example. The placebo effect is well known, but it has been investigated primarily in the context of pain syndromes.

This has led investigators to focus on changes in brain activity, as they appear to provide the most likely substrate for the occurrence. Nevertheless, the biological mechanisms responsible for the impact remain elusive. A group of researchers led by Karin Meissner in LMU’s Institute of Medical Psychology, in collaboration with colleagues located at the Helmholtz Zentrum München, has now carried out the first study of the placebo effect at the molecular level, in the context of the relief of nausea.

Their results not only confirm the efficacy of a placebo on symptoms, they also reveal changes in the chemistry of the blood that could explain the effect itself.

Nausea is all too familiar to travelers who are prone to sea sickness brought on by the constant and unpredictable motion of the ocean surface. But nausea occurs in a number of other settings – including pregnancy – and as a consequence of prescription drugs or anesthetics.

Up to now, relatively few studies have been devoted to the function or effectiveness of the placebo effect in the treatment of nausea. “I find nausea as a symptom particularly interesting, because it is associated with measurable changes in the action of the stomach,” Meissner explains. This gives an objective physical parameter with which the mysterious placebo effect may be tracked.

The researchers first exposed a cohort of 100 volunteers to a visual stimulus known to induce nausea. More specifically, they were shown a continuing succession of black and white stripes displayed on a semicircular display 30 cm away. Their reactions to the vection stimulus, which induces the illusion of self-motion, were then assessed.

The subjects were asked about their symptoms, their degrees of gastric activity were measured and blood samples were obtained, which were subsequently subjected to proteomic analysis. On the next day, the team analyzed how various subgroups of their experimental population reacted to a placebo compared to either an effective treatment or no treatment in any way.

In the event of the proven treatment, a transcutaneous electrical neural stimulator (TENS device) was used to deliver mild electrical impulses to particular acupuncture points on the skin. In the case of the placebo group, the treatment was applied only superficially to the skin or the device wasn’t switched on at all.

The results were astounding, insofar as they seemed to confirm a few of the hypotheses that have been advanced to explain the placebo effect in the scientific literature, says Meissner. For instance, proteomic analysis of the blood of the experimental subjects revealed the existence of particular proteins that have been linked to a rapid immune response to nausea.

“And in our study, the placebo treatment seems to repress this immune response,” says Meissner. Additionally, there are signs that proteins such as neurexin and reelin, which have been connected to empathetic behavior and bonding, might be related to the placebo effect on the relief of nausea.

This suggests that hormones related to bonding may amplify the placebo effect – and it can point to an evolutionary origin of the phenomenon. “In social mammals, grooming behaviour strengthens bonding,” Meissner points out. This is a form of social hygiene – a term which could be also applied to a placebo treatment – and could trigger the release of certain hormones which support the impact of the placebo, she adds.

Finally, the proteomic signatures found in blood plasma were able to forecast with surprising accuracy which of the participants could create the very best response to the placebo, Meissner says. One other noteworthy observation was made during the study in relation to the impact of the placebo.

This parameter returned to normal in women who received the placebo treatment, but did not react in the corresponding male cohort. “The reasons for this sex-related gap are not yet understood,” says Meissner.

“But they could be connected with differences between the sexes in regard to how individuals adapt to painful stimuli.” She and her co-authors view the new study as a promising first step, as it underlines the potential of proteomic investigations in clinical research.