Manipulating the placebo effect

03 July 2018

Interview with

Arvina Grahl, University Medical Centre Hamburg-Eppendorf

The word placebo means “I will please” in Latin, and it’s the phenomenon that, if someone thinks something is going to help them then they get benefit even if the thing does absolutely nothing. But how much benefit the person gets depends heavily on their expectations, and those, it turns out are coloured by the reliability and reproducibility of their past experiences. Arvina Grahl subjected volunteers to mild heat pain which she relieved with a fake “TENS” device. For some of the participants she tweaked the pain levels to make it look like the TENS device delivered less reliable relief. For others it worked well every time. As she explained to Chris Smith, the question was how would this affect the performance of the placebo effect, and how would it be reflected in brain imaging measurements…

Arvina - So what we actually wanted to address here was to create two different groups and present a painful stimulus which we did with heat pain. One group with very precise expectations about the efficacy of the treatment. And one group with more unreliable expectations concerning this treatment, and the idea was to see that the group that had much more precise expectations concerning this treatment would benefit from this precision because that information were much more reliable concerning the efficacy of that treatment compared to the other group. This would mean that the placebo effect would be larger for the more precise group compared to this group with more unreliable information.

Chris - What was the nature of the treatment that you gave them for the thermal pain?

Arvina - So the treatment we told our participants that it is an electrical stimulation which is called TENS it is well know. We used this to tell them this would help to give you some pain relief during this thermal stimulation but actually we never applied this.

Chris - And how did you then factor in the precise information versus the imprecise information situation? So there was that variation between the two groups, how did you do that?

Arvina - A classic placebo study always works that you present your participants with two conditions; a treatment condition and a non treated controlled condition, and then the second phase would be that you present the same thing again but in the first phase we don't tell our participants that we present them two different intensities are more painful for the control and a less painful for the treated to let them really experience this treatment effect. And in the group with the high precision, we actually presented as this lower intensity always the same intensities of pain, and then the other group where we wanted to create some unreliable information some more variable information we actually varied treatment effects or sometimes that was more pain relieving and sometimes there was less pain relieving.

Chris - So in other words they dont realise it but you're making the stimulus change so that its more or less painful and they think its because the pain relief is better. Its not. Its because youre actually subjecting them to more discomfort and then youre using that to make them think they're getting relief.

Arvina - Thats exactly what we do. We will always tell them for the whole experiment, it is always the same pain intensity that they would get and due to the treatment they will feel a certain relief.

Chris - And what happens?

Arvina - As we did this experiment also in the fMRI scan where we have a look at the brain responses as well, and wanted to see if the brain processes the pain differently when we induce different expectations. We first see in the behaviour that the placebo effect was actually nearly none present in this more unreliable information group, and much larger in this higher precision group. And we also could see that this was modulated in the brain in a very well-known area called the P G.

Chris - This is the Periaqueductal gray matter isnt it? It's where theres a centre of endogenous opioid activity in the nervous system.

Arvina - Exactly. Its a very exciting area actually because it has strong modulating influences on the pain perception, also in pain that incoming and also pain that was processed in a brain and this feedback back to the skin for example whether painful stimulation was presented. Butt what we actually see which is very interesting is we see a higher activation for those participants that had the more unreliable expectations prior to this test phase. So we see that there is more modulation needed if you have more unreliable information concerning the treatment.

Chris - That sounds a bit counterintuitive one would expect that you'd see more activity if you were seeing more reliable pain relief. So how do you account for that?

Arvina - We actually referred that to two different resource demanding processes. So when we know that expectations are very reliable, when we see that there is less activation needed to process this information because there are already similar to those that I expect then you need less resources in this modulatory area.

Chris - And can we utilise this information now to try and work out a way of exploiting this mechanism to a better effect?

Arvina - I would say it is important that a physician actually asks for expectations of a treatment and assesses was the patient actually experienced in other treatments to increase the expectation effect of the treatment in combination with the actual treatment.


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