The study, examining the placebo effect, shows that the brain releases chemicals that relieve pain in patients who believe they're being treated.
It is to be published Wednesday in the Journal of Neuroscience.
Researchers say the findings could lead to new ways to treat chronic pain.
"This deals another serious blow to the idea that the placebo effect is a purely psychological, with no physical basis," said Dr. Jon-Kar Zubieta, associate professor of psychiatry and radiology at the Michigan Medical School. "The mind-body connection is quite clear."
While previous studies at Michigan and elsewhere have shown how the brain reacts physically to placebos, researchers said this study is the first to pinpoint a specific brain chemistry mechanism.
The study involved 14 healthy men, ages 20 to 30, who were given a salt water injection that caused pain to their jaw. They were then injected with a placebo and told it was a painkiller.
Researchers asked the men questions and monitored their brain activity during the process.
For each of the men, their brains released more natural painkilling endorphins after the placebos were administered. Nine were classified as high placebo responders, while five were classified as low responders.
The scientists say further research is needed to determine if the results hold up in women and people with various illnesses.
The research was funded by the National Institutes of Health and completed by researchers at Michigan's Molecular and Behavioral Neurosciences Institute.