Brain circuits offer placebo effect pain relief
Published in Nature, research led by the UNC School of Medicine reveals a new pain control pathway in the brain.
Proven by researchers’ best double-blind randomized clinical trials, the placebo effect is very real, yet mysterious. Now neuroscientists have discovered a key piece of the puzzle.
Publishing in Nature, researchers at the UNC School of Medicine – with colleagues from Stanford, the Howard Hughes Medical Institute and the Allen Institute for Brain Science – found a pain control pathway in the brain.
The researchers then showed that certain neurons and synapses along this pathway are highly activated when mice expect pain relief, with the mice experiencing pain relief even when no medication is involved.
“That neurons in our cerebral cortex communicate with the pons and cerebellum to adjust pain thresholds based on our expectations is both completely unexpected, given our previous understanding of the pain circuitry, and incredibly exciting,” said Greg Scherrer, who led the research. He is an associate professor in the medical school’s cell biology/physiology and pharmacology departments and the UNC Neuroscience Center. “Our results do open the possibility of activating this pathway through other therapeutic means, such as drugs or neurostimulation methods to treat pain.”
Scherrer and colleagues said research provides a new framework for investigating the brain pathways underlying other mind-body interactions and placebo effects beyond the ones involved in pain.
Placebo paradox
In the face of pain, the brain releases chemicals to help us feel better. The placebo effect – feeling better even though there was no “real” treatment – has been documented as a very real phenomenon for decades.
In clinical research, the placebo effect is often seen in what we call the “sham” treatment group. That is, individuals in this group receive a fake pill or intervention that is supposed to be inert; no one in the control group is supposed to see a benefit. But the brain is so powerful and the desire to feel better so strong that some experience a marked improvement in their symptoms. Some individuals are convinced they received a real treatment meant to help them.
In fact, it’s thought that some individuals in the “actual” treatment group also derive benefit from the placebo effect. This is one of the reasons why clinical research of therapeutics is so difficult and demands as many volunteers as possible so scientists can parse the treatment benefit from the sham. One way to help scientists do this is to understand what precisely is happening in the brain of someone experiencing the placebo effect.
Enter the Scherrer lab
The authors of the Nature paper knew that the scientific community’s understanding of the biological underpinnings of pain relief through placebo analgesia – when the positive expectation of pain relief is sufficient for patients to feel better – came from human brain imaging studies, which showed activity in certain brain regions. Those imaging studies did not have enough precision to show what happened in those brain regions.
Scherrer’s team designed a set of meticulous, complementary and time-consuming experiments to find out. These experiments helped them see and study the intricate neurobiology of the placebo effect down to the brain circuits, neurons and synapses throughout the brain.
The scientists found that when mice expected pain relief, that expectation boosted signals along this pathway.
“We all know we need better ways to treat chronic pain, particularly treatments without harmful side effects and addictive properties,” Scherrer said. “We think our findings open the door to targeting this novel neural pain pathway to treat people in a different but potentially more effective way.”
