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Why Placebo Effect Varies From Person To Person

Why Placebo Effect Varies From Person To Person
Why do some people experience a placebo effect that makes them feel better when they receive a sham therapy they believe to be real while other people dont respond at all to the same thing, or even feel worse".

A new study from the University of Michigan Health System may help explain why.

Using two different types of brain scans, U-M scientists have observed that the extent to which a person responds to a placebo therapy is closely associated with how active a certain area of their brain becomes when theyre anticipating something beneficial.

Specifically, the research finds strong links between an individuals response to a placebo painkiller, and the activity of the neurotransmitter known as dopamine in the area of the brain known as the nucleus accumbens. Thats a small region at the center of the brain thats involved in our ability to experience pleasure and reward, and even to become addicted to the high caused by illicit drugs.

The new research, reported in the July 19 issue of the journal Neuron, builds on research previously published by the same U-M team in 2005. That study was the first to show that just thinking a placebo medicine will relieve pain is enough to prompt the brain to release its own natural painkillers, called endorphins, and that this corresponds with a reduction in how much pain a person feels.

Receptors for both endorphins and dopamine are clustered heavily in the nucleus accumbens. So, taken together, our studies delve directly into the mechanisms that underlie the placebo effect, says senior author and U-M neuroscientist, psychiatry expert and brain-imaging specialist Jon-Kar Zubieta, M.D., Ph.D. This is a phenomenon that has great importance for how new therapies are studied, because a number of patients respond just as well to placebo as they do to an active therapy. Our results also suggest that placebo response may be part of a larger brain-resiliency mechanism.

For the current study, Zubieta and colleagues led by neuroscience graduate student David J. Scott combined information from two types of brain scan to come to their conclusions. They performed PET (positron emission tomography) scans on the brains of 14 healthy volunteers, and fMRI (functional magnetic resonance imaging) scans on those 14, and on 16 other healthy volunteers.

The PET scans focused on brain dopamine, looking at its activity as volunteers were told to expect, and then received, a painful injection of saline solution in their jaw muscle. They were then told to expect, and then received, an injection that they were told could either be a painkiller or a placebo. (Both were in fact placebos.) The fMRI scans looked at volunteers brains while they played a game. Before each round, they learned that a correct answer would win or lose an amount of money, up to $5.

The PET scans were made using 11C-raclopride, which combines a drug that binds preferentially to dopamine receptors with a short-lived radioactive form of carbon that can be seen on PET scans. Throughout the PET scanning session, volunteers were asked to rate their level of pain on a numerical scale, and to describe any emotions they were experiencing.

Before the painful injection began, but after the volunteers had been told it was coming, they were also asked to guess how much pain relief theyd get from the painkiller if they received it. Half the volunteers were women, all in the same stage of their monthly cycle to avoid differences in hormonal state that might affect tolerance of pain another topic that Zubietas team has studied.

The PET scans and pain ratings revealed that as a group, the volunteers experienced significant pain relief from the placebo. But when scientists looked at each individuals results, they observed that only half of the volunteers reported less pain when they received the painkiller placebo.

These placebo responders, as they were dubbed, had significantly more dopamine activity in their left nucleus accumbens than the other volunteers, beginning when they were told the painkiller medicine was about to begin flowing into their jaws. It also turned out that these individuals had also all anticipated the painkiller would give good pain relief before they even received it.

Meanwhile, of the seven individuals who didnt experience the placebo effect, four actually reported feeling more pain when the painkiller was delivered a phenomenon that has been dubbed the nocebo effect and has been observed in other situations.

Just to make sure that the volunteers pain ratings werent affected by the fact that they always received painful injections followed by placebo painkiller, the scientists put a separate group of 18 male volunteers through the same experience twice, but no placebo was actually given, and actual PET scans were not done. Their pain and emotion ratings were significantly different from those of volunteers who received placebo.

The results of these functional molecular imaging studies indicate that dopamine activity is activated in response to a placebo in a manner thats proportional to the amount of benefit that the individual anticipates, says Zubieta, who is the Phil F. Jenkins Professor of Depression in the U-M Medical Schools Department of Psychiatry and a member of U-Ms Molecular and Behavioral Neuroscience Institute, Depression Center and Department of Radiology.

The fMRI scans, which were performed on different days from the PET scans, revealed additional information about how individual expectations correlated with their placebo response. Each volunteer had an fMRI scan that looked at blood oxygenation throughout their brain, which allows scientists to spot areas where neurons (brain cells) are particularly active as the individual performs a task or plays a game. In this case, the task was a very simple gambling game, in which subjects were scanned while expecting varying levels of a monetary reward or no reward.

As in the PET scans, the nucleus accumbens was a hotbed of activity as the volunteers were told how much money they could win or lose in the next round; as they waited for the round; and as they pressed the button and learned if they had succeeded in winning or avoiding losing money.

Then, the scientists compared the PET and fMRI scans for the volunteers who had had both types of scan. They also compared the ratings of anticipated placebo effect, the analgesia induced by the placebo during the pain studies, and the emotional changes linked to it. They observed that those who expected a placebo to help them and got greater benefit from it (more analgesia, better emotional state) were also those who had the most activity in their nucleus accumbens during the anticipation of receiving a reward in the fMRI money game.

Posted by: Janet    Source

Did you know?
Why do some people experience a placebo effect that makes them feel better when they receive a sham therapy they believe to be real while other people dont respond at all to the same thing, or even feel worse". A new study from the University of Michigan Health System may help explain why. Why Placebo Effect Varies From Person To Person

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