Sometimes, just thinking you are receiving treatment is enough to make you feel better, a phenomenon known as the placebo effect. Scientists have long wondered what causes this outcome, the magnitude of which is not the same for all people. A new brain imaging study suggests that the body's natural painkillers, endorphins, play a significant role.

Previous studies had shown general changes in brain activity associated with the placebo effect by using functional magnetic resonance imaging, and scientists had hypothesized that the brain's opioid system was involved. This time, by utilizing positron emission tomography (PET) brain scans for the new work, the researchers were able to focus on a specific type of brain receptor and track its response to a placebo. The PET scans employed by Jon-Kar Zubieta of the University of Michigan and his colleagues measured the activity of mu-opioid receptors, which are an integral part of the body's natural painkilling system and help transmit pain signals from one nerve cell to the next. The team asked 14 healthy male volunteers to undergo the slightly painful but harmless procedure of having saltwater injected into their jaws. Over the course of a 20-minute procedure, volunteers recorded the intensity of their pain every 15 seconds and then summarized their experience afterward. In a randomized trial, some subjects received an analgesic medication, whereas others were told they were being given medication, but received none.

According to a report published today in the Journal of Neuroscience, all of the participants who were told to expect medicine but got a placebo instead showed an increase in the activity of their endorphin system. Four brain regions were involved and activity in specific areas was also associated with the subjects' own descriptions of the pain they felt. For example, activity in the dorsolateral prefrontal cortex correlated to how effective the volunteers were expecting the medicine to be at relieving their pain.

The results are the first direct evidence that endorphins can help explain the placebo effect. "This deals a serious blow to the idea that the placebo effect is a purely psychological, not physical, phenomenon," Zubieta says. "We were able to see that the endorphin system was activated in pain-related areas of the brain, and that activity increased when someone was told they were receiving a medicine to ease their pain." The results may not apply to all groups, however, and further investigation is needed to determine variations based on age, gender and confounding factors such as illness.

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