Brain's'Pleasure Chemical Is Involved In Response To Pain Too, Study Shows

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Brain's " 'Pleasure Chemical " Is Involved In Response To Pain Too,

Study Shows

http://www.medicalnewstoday.com/medicalnews.php?newsid=54587

For years, the brain chemical dopamine has been thought of as the

brain's " pleasure chemical, " sending signals between brain cells in

a way that rewards a person or animal for one activity or another.

More recently, research has shown that certain drugs like cocaine

and heroin amplify this effect - an action that may lie at the heart

of drug addiction.

Now, a new study from the University of Michigan adds a new twist to

dopamine's fun-loving reputation: pain.

Using sophisticated brain-scanning and a carefully controlled way of

inducing muscle pain, the researchers show that the brain's dopamine

system is highly active while someone experiences pain - and that

this response varies between individuals in a way that relates

directly to how the pain makes them feel. It's the first time that

dopamine has been linked to pain response in humans.

The finding, published in the October 18 issue of the Journal of

Neuroscience, may help explain why people are more likely to acquire

a drug addiction during times of intense stress in their lives. It

may also yield clues to why some, but not other chronic pain

patients may be prone to developing addictions to certain pain

medications. And, it gives further evidence that vulnerability to

drug addiction is a very individual phenomenon - and one that can't

be predicted by current knowledge of genetics and physiology.

" It appears from our study that dopamine acts as an interface

between stress, pain and emotions, or between physical and emotional

events, and that it's activated with both positive and negative

stimuli, " says senior author Jon-Kar Zubieta, M.D., Ph.D., professor

of psychiatry and radiology at the U-M Medical School and a member

of the U-M Molecular and Behavioral Neuroscience Institute and U-M

Depression Center. " It appears to act as a mechanism that responds

to the salience of a stimuli - the importance of it to the

individual - and makes it relevant for them to respond to. "

The study, which involved 25 healthy men and women, showed that

dopamine was active in areas of the brain region known as the basal

ganglia, the same region where it has been observed to respond to

positive stimuli, such as food or sex.

But when the researchers induced pain in the volunteers' jaw muscle,

and asked them to rate different aspects of how they were feeling,

differences emerged in specific sub-areas of the basal ganglia. For

example, the more a person rated the pain as causing emotional

distress and fear, the more dopamine was released in the area known

as the nucleus accumbens - the same region implicated in drug

addiction.

That effect persisted even after the researchers controlled for the

negative emotional effects caused by the actual research setup,

which included a needle inserted into a large jaw muscle, and the

expectation of pain and repeated questioning.

Similarly, dopamine release in two other areas of the basal ganglia -

the putamen and caudate nucleus - was strongly correlated with the

rating of how intense and unpleasant the pain itself was on a scale

of 0 to 100. The authors concluded that in some areas of the basal

ganglia, dopamine was involved in the assessment of pain itself,

while in the ventral area, or nucleus accumbens, it was related to

the emotional experience of pain.

The study used positron emission tomography, or PET, scanning that

allowed the researchers to calculate the level of dopamine activity

by measuring the percentage of dopamine receptors on the surface of

brain cells that were active. To do this, they used the drug

raclopride, to which had been attached a short-lived radioactive

form of carbon. The drug binds to the same receptors that dopamine

does, so the more of it that could be seen in a specific brain area,

the less dopamine was present and vice versa.

The researchers also scanned each volunteer's brain using magnetic

resonance imaging (MRI) in order to create a precise map of the

brain's structure, and combined that with their PET scans to find

the exact areas of dopamine activity.

The volunteers answered questions from two standardized

questionnaires repeatedly both in a control (no pain) state and when

their jaw muscles were being injected with harmless salt water in

order to cause pain. The questionnaires measure pain and emotion in

a standardized way, so that ratings can be compared over time. None

of the participants had a history of medical or psychiatric illness,

nor of drug addiction or dependence. The 7 female volunteers were

not taking birth control pills and were scanned at the same point in

their menstrual cycles.

In addition to the differences in dopamine receptor activation in

certain areas of the brain across all the participants, the scans

also revealed differences between individuals in the level of their

dopamine response and their self-rated pain and emotional response.

This kind of variation may help explain the major variation between

individuals who are exposed to addictive drugs - some become

addicted to the pleasures of the " high " the drugs cause, while

others do not.

" Variations in risk for drug abuse after initial exposures could be

mediated by individual differences in the response of this

neurotransmitter system to various forms of stress, with pain being

itself a physical and emotional stressor, " write the authors, led by

J. , Ph.D., a graduate student at MBNI. " The dopamine

system in the ventral basal ganglia may represent an important point

of interaction between the neurobiologies of emotion, reward and

pain regulation.

The new findings build on previous pain research by Zubieta and his

team, which has shown individual variation in the rating of pain,

and has visualized the brain's own painkiller system responding to

pain and even to the giving of a " placebo " painkiller medication.

Now, the team is working to examine the hormonal and genetic factors

that may be different between people whose dopamine systems

responded differently to pain. They also have recently received

funding from the National institute of Drug Abuse to study

individual variation in the effects and use of opioid painkiller

drugs among people with chronic pain.