The study, funded by the National Institutes of Health, provides the first concrete evidence that endorphins, the brain’s own pain-fighting chemicals, play a direct role in the phenomenon known as the placebo effect.

Endorphins behave similarly to opiate drugs, such as heroin and morphine. They bind to receptors and stop the transmission of pain signals along the nerve pathways. Previous studies have indicated that the brain responds physically during the placebo effect, but the new study is the first to pinpoint a specific mechanism that triggers the brain's physical response.

"This deals another serious blow to the idea that the placebo effect is a purely psychological, not physical, phenomenon," says lead author Jon-Kar Zubieta, MD, PhD, associate professor of psychiatry and radiology at the U-M Medical School and associate research scientist at the Molecular and Behavioral Neurosciences Institute.

The study involved 14 young men who agreed to allow researchers to inject their jaw muscles with a concentrated salt-water solution to induce pain. Brain scans were performed on the subjects to monitor the activity of their brains' natural painkilling endorphins during the process.

Mind-Body Connection Clear

During one scan, they were told they would receive a medicine (in fact, a placebo) that might relieve pain. Subjects reported a lessening of pain after receiving the placebo, and brain scans indicated increased endorphin activity in four areas of the brain known to be involved in the response to, and processing of, pain.

Every fifteen seconds, the subjects were asked to rate the intensity of their pain on a scale of 0 to 100. After each scan, the researchers asked the participants more questions about their mood, emotions and other aspects of how they felt during the scans.

There were significant differences between ratings given by participants after the scan in which they received the placebo compared to the scan during which they received the jaw injection alone.

"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. They then reported feeling less pain. The mind-body connection is quite clear," reports Zubieta.

Suggestion Triggers Endorphin Release

Another scan was performed in which subjects were administered additional placebo prior to increased pain-induction to discern whether endorphin activity could be stimulated solely by suggestion.

As additional placebo was administered, endorphin activity increased. Researchers then had to increase the amount of salt-water in order to maintain the subjects' pain levels, which they did without their knowledge.

Two-thirds of the study participants were classified as "high placebo responders," experiencing significant endorphin activity through the power of suggestion. This helps explain why so many people report relief after receiving therapies and remedies that provide no actual physical benefit.

This new information may lead to better use of cognitive, or psychological, therapy for people with chronic pain, the authors suggest.

Researchers used positron emission tomography (PET) scans to determine exactly which part of the brain the endorphin activity originated from, cross-registering them with magnetic resonance imaging (MRI) scans for the purposes of accuracy.

The results will be published in the August 24 issue of the Journal of Neuroscience.