It has been well documented in medical literature that when people believe they are receiving treatment, they will actually experience a reduction in symptoms—even if their “treatment” is an inactive placebo. This is particularly true when it comes to pain reduction, or analgesia; patients who believe they are being given powerful medication for pain will actually experience a drop in discomfort, even if no active pain medication has been administered. Yet what is it about how the brain is wired that causes this effect?

A group of neuroscientists and psychologists from Hamburg, Germany believe that patients’ expectations of pain relief in part cause the brain to produce its own natural painkiller—previous studies have shown that expectation increases the production of endogenous opioids, which are generated in sophisticated frontal parts of the brain associated with pain regulation. Yet, in addition to this, the researchers found that a more primitive pain processing network was also employed—the opioidergic descending pain control system, which links up to the deeply seated amygdala, hypothalamus and other regions and can inhibit pain processing in the spinal cord, thereby minimizing pain responses in the brain.

In a study published in the August 27 issue of the journal Neuron, the researchers recruited 48 men for a three day trial, during which they were given a cream, applied to the forearm. Half of the participants were told that the cream was a painkiller, while the other half weren’t (presumably they thought it was just a moisturizer). On the first day, the subjects were exposed to mild pain stimulation on the region of the arm where the cream had been applied. Each day after, they underwent the same stimulation, but the researchers secretly lowered the intensity. Through all of this, researchers kept track of brain activity using a technique called pharmacological functional magnetic resonance imaging (fMRI).

In addition to the cream, participants were also given an injection—either with a control saline solution, or with the drug naloxone, which has been shown to block the body’s opioids, or painkillers. What they found was, among patients led to believe they’d been given an analgesic cream, there was a marked placebo effect—they reported an average pain reduction of 23% compared with the control group (who, again, actually had the same cream). Yet they also found that, in the group whose pain reduction capacity was blocked by the naloxone—in contrast with those given saline—the placebo effect was much less powerful. Those who received saline experienced a 36% reduction in pain, compared with only a 10% reduction on the naloxone. There was no significant difference among the control group, with or without naloxone.

Throughout the trial, the brain scans showed that, in the placebo group given naloxone, pain reduction responses were dulled in the brain. What’s more, when the placebo effect was evident, the researchers saw connectivity between the brain’s frontal, more sophisticated pain processing hubs and the descending pain control system, which regulates pain processing beginning in the spine. Going forward, they suggest, new research could help reveal just what roles this system plays in other types of pain regulation beyond the placebo effect, perhaps even helping clarify the neurological basis for pain reduction techniques such as hypnosis.