How Fake Treatments Reduce Real Pain
The brain and the spinal cord.
Credit: NIH, NIDA

People who think a placebo treatment for pain is working in fact experience reduced pain signaling in their spinal cord, according to a new study.

A placebo is a treatment that is thought to have no effect and which is often given to study participants as a control, to compare the effects of "nothing" to the effects of an actual treatment. But studies in the past have shown that, inexplicably, placebos can have positive effects.

The new results suggest that the pain-related placebo effect may work by tapping into a pain-suppressing system already in place in the body, one that starts in the brain and relays down to the spinal cord.

Scientist know that when people experience a decrease in pain from a placebo, certain compounds, called endorphins, are released in their brains. But they don't know exactly how the release of those compounds leads to pain reduction.

One idea is that the endorphins allow certain parts of the brain to "communicate with an evolutionarily preserved system in the brain stem," one that controls pain by inhibiting neural activity in the spinal cord, said Falk Eippert, a researcher from the Department of Systems Neuroscience at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

Eippert and his colleagues tested this hypothesis in a group of 15 volunteers. The subjects were told they would receive a painful heat stimulation on their forearm, and during the stimulation, their arms would be treated with one of two possible creams – one which was an active, pain-relieving cream, (called a lidocaine cream) and the other which was an inactive control. In truth, both creams were inactive and were not designed to reduce pain in any way.

First, the researchers applied the full heat stimulation to the subjects' forearms that had been treated with the control cream. But when they tested the so-called "lidocaine" cream, they reduced the heat temperature so the subjects felt less pain, a trick designed to make the volunteers think that the "lidocaine" cream actually had an effect.

"We wanted to induce a belief in the effectiveness of this treatment, the cream, although it doesn't have an effectiveness, per se," said Eippert.

Then, the researchers ran the heat-stimulation experiment again, but this time, they did not reduce the heat temperature during the "lidocaine" treatment. During the heat stimulation experiment, the team studied the volunteers with functional magnetic resonance imaging (fMRI) to observe the spinal cord response.

The fMRI images can show the amount of oxygenation in the blood, which is an indirect measure of the spinal cord's neural activity.

When the subjects were given the control cream, they reported a lot of pain, and showed strong activity in their spinal cord. But when the volunteers received the so-called "lidocaine" treatment, which they thought was real but which was in fact a placebo, they reported less pain and showed less activity in their spinal cord. This suggests that "there must be some inhibition [coming] from the brain," said Eippert.

The researchers believe the placebo effect works by recruiting the ancient pain-suppressing system.

"What we can now show is that, in humans, this system is brought into play by psychological factors such as expectation of pain relief under placebo," said Eippert. Moreover, it shows that the placebo effect is something very profound, he said, "It's not just altered reporting behavior, it’s a very deeply rooted effect."

With only 15 subjects, the study might seem rather small, but it is actually quite a good size for an imaging study, which often have between 10 and 20 subjects, said Eippert. He also notes that the placebo effect is very robust, and thus you do not need too many people to study it. A study looking at a smaller behavioral effect might need more subjects.

The data was also analyzed in a way that accounted for the small study size. "The kind of statistics that we're using are explicitly taking into account how many subjects we had," said Eippert. Their results showed that the reduced activity in the spinal cord in response to the placebo was statistically significant.

The study will be published in the Oct. 16 issue of the journal Science.