Fake drugs vs. real drugs… How does the brain relieve pain even when taking fake drugs?

A new animal experiment study has shown that the placebo effect actually produces a pain-suppressing effect in the brain circuitry. This is what the scientific journal Nature reported on the 24th (local time) based on a paper by American researchers published in its own journal.

The placebo effect is when pain is relieved by deceiving people into believing that it is a painkiller and giving them a substitute (such as sugar). The biological mechanism of this phenomenon, also known as the placebo effect in Korean, has remained a mystery until now.

A research team led by Professor Gregory Shirer (neurobiology) of the University of North Carolina in the United States tracked which brain regions were activated in mice placed in an experimental situation designed to expect pain relief, just as one might expect a placebo effect when taking a placebo. Surprisingly, the cerebellum and brainstem, known to be responsible for movement and control, were discovered to be activated regardless of pain perception.

“We didn’t know specifically how the placebo effect worked and whether it was real,” said Clifford Wolf, a professor of neuroscience at Harvard who reviewed the paper. “This study shows that it’s a real, specific phenomenon.” Professor Scherer, the study’s lead author, said the findings could lead to new ways to treat pain, adding, “It could lead to the development of entirely new types of drugs.”

Previous imaging studies in people have shown that pain relief from placebos is associated with activity in brain regions called the brainstem and anterior cingulate cortex. To investigate this further, the researchers designed an experiment in mice in which they expected placebo-like pain relief. Using two rooms, one with a comfortably warm floor and one with a painfully hot floor, the animals were conditioned to expect that the pain they felt when stepping on the hot floor would be relieved when they entered the cool room.

Using real-time imaging tools, the researchers identified a group of neurons in the brainstem that were activated during the placebo experiment. These were neurons located in the pontine nucleus (Pn), a brain region that connects the cerebral cortex and the cerebellum. The Pn is not known to be associated with pain.

To better understand the role of the nucleus accumbens neurons in pain relief, the researchers measured the effects of blocking the activity of these neurons. When the nucleus accumbens neurons were inhibited, mice moved to the hot floor licked their paws, raised their bodies, and jumped more frequently, indicating that the pain was not relieved. On the other hand, mice with activated nucleus accumbens neurons took longer to lick their paws, indicating that the pain was relieved.

The researchers reported that 65 percent of the 4,932 neurons in the pons nucleus had opioid receptors, which produce effects similar to those of powerful opioid painkillers.

In addition, neurons with opioid receptors were found to extend to three areas of the cerebellum. This is a completely new discovery, as pain relief could not be expected from the cerebellum before. The researchers confirmed that during the placebo experiment, the Purkinje cell group, the main cell group in the cerebellum, became more and more active. Professor Wolf pointed out that “endogenous opioids are almost certainly involved here.”

The study could lead to new, more effective painkillers. It could allow scientists to explore how to connect the neural circuits of the brainstem and cerebellum without relying on placebos. Future research could also find ways to “make the body’s own regulatory mechanisms that suppress the experience of pain more reliably activated,” Wolf said. Understanding these brain circuits could also help explain why pain treatments like cognitive behavioral therapy and transcranial magnetic stimulation actually work.

But exactly what triggers the placebo effect remains a mystery. “We still don’t know why the placebo effect occurs in some individuals and not everyone, and why it fades over time,” Wolff said.

The paper can be found at the following link (