Placebo effect on brain can ease some pain

Washington -- When it comes to the placebo effect and pain relief, the brain appears to be a much more active player than has been recognized up to now.

Not only does the brain stem play a role, but the cognitive areas of the brain also get involved, according to a study published in the Aug. 24 Journal of Neuroscience. Parts of the brain that effect such complex activities as thought, emotion, reward and response to pain are all activated when a person thinks that pain relief is on the way, said Jon-Kar Zubieta, MD, PhD, lead author and an associate professor of psychiatry and radiology at the University of Michigan Medical School.

This conclusion adds to a growing body of evidence that the placebo effect is very real and that better use of cognitive therapies might lead to more effective treatments for people with chronic pain.

The study also gives direct evidence that endorphins play a vital role in the placebo effect. "We were able to see that the endorphin system was activated in the brain's pain-related areas, and that activity increased when someone was told they were receiving a medicine to ease their pain," Dr. Zubieta said. "They then reported feeling less pain. The mind-body connection is quite clear."

The findings are based on sophisticated brain scans of 14 young, healthy men who agreed to allow researchers to inject their jaw muscles with a concentrated salt water solution to cause pain. The injection was made while they were having their brains scanned by a positron emission tomography scanner. During one scan they were told they would receive a medicine that might relieve pain. The medicine was actually a placebo.

Every 15 seconds during the scans, the men were asked to rate the intensity of their pain on a scale of zero to 100. The researchers correlated the ratings with their PET scan images, which revealed the activity of endogenous opioids, which are the brain's natural painkilling endorphin chemicals.

The placebo, a small amount of hydrating solution, was given intravenously every four minutes. As the researchers alerted the participants that the placebo was coming, the amount of additional concentrated salt water needed to maintain participants' pain over time was increased, indicating a reduction in pain sensitivity that allowed the participants to tolerate more salt water than before.

Dr. Zubieta is next moving on to larger studies that include women. He and his colleagues recruited only healthy young men for this study to rule out the impact that chronic pain, mood disorders and hormone variations might have on the endorphin system. Future studies also will examine why some participants responded more strongly than others to the placebo effect.

Perhaps surprisingly, given the nature of the research, Dr. Zubieta said he had no difficulty recruiting sufficient numbers of participants, who are paid about $200 for each of three sessions.

People are attracted to the studies because they are curious, he said, not necessarily because they need the money. Plus, the level of pain is moderate, usually rated at about 30 on a scale of 100.

"We want it to be more like what people feel in actual pain conditions," he said. The pain is often described by participants as aching or throbbing. "We have never had a person withdraw because of the pain."

The study was given high marks by Donald D. Price, PhD, professor of oral and maxillofacial surgery at the University of Florida College of Medicine in Gainesville. "The way I view this is that the placebo analgesic effect is very complicated and involves the patient hearing the suggestion, seeing the treatment and watching the treatment," he said. "It requires a lot of cognition and a lot of the brain has to get involved in that kind of response. This paper shows that pain inhibition is not just a knee-jerk response, it involves mental activity on the part of the patient."

This area of research is becoming more active, and the science is dovetailing with the development of policy, he added.

One such development was the publication last spring of a position statement by the American Pain Society, which includes as an ethical tenet that physicians and others must not use a placebo to determine whether a patient's pain is real or not.

Placebo effects potentially can occur in any treatment, Dr. Price noted in a commentary that accompanied the publication of the APS statement. Part of pain relief includes the patient's perception of the therapeutic intervention.

"The perception leads to the expectation of relief, and that in turn activates endogenous pain inhibitory systems which in turn produce more pain relief," he said.