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Updated 10:00 AM October 30, 2006




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Study shows brain's pleasure chemical is involved
in response to pain, too

For years, 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 U-M study adds a new twist to dopamine's fun-loving reputation: pain.

Using sophisticated brain scanning and a carefully controlled way of inducing muscle pain, 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 Oct. 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 also may yield clues to why some chronic pain patients may be prone to developing addictions to certain pain medications.

It also gives further evidence that vulnerability to drug addiction is a very individual phenomenon—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 Dr. Jon-Kar Zubieta, professor of psychiatry and radiology at the Medical School and a member of the Molecular and Behavioral Neuroscience Institute (MBNI) and the 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 responding to positive stimuli such as food or sex.

But when the researchers induced pain in the volunteers' jaw muscles, and asked them to rate various aspects of how they were feeling, differences emerged in specific subareas 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.

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 volunteers responded to two standardized questionnaires repeatedly, while 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.

In addition to the differences in dopamine receptor activation in certain areas of the brain across all the participants, the scans also revealed disparities between individuals in their dopamine response levels and their self-rated pain and emotional response. This kind of variation may help explain the major differences between individuals who are exposed to addictive drugs—some become addicted to the pleasures of the "high" the drugs cause, while others do not.

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.

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.

In addition to Zubieta, the study's authors include David Scott, a graduate student at MBNI, Mary Heitzeg of MBNI and psychiatry; Robert Koeppe, a professor of radiology and director of the PET Physics Section in the Division of Nuclear Medicine; and Dr. Christian Stohler, dean of the Dental School at the University of Maryland and formerly of the U-M Dental School. The study was funded by the National Institutes of Health.

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