Researchers have identified a new pathway in the brain that plays a crucial role in controlling pain. This pathway connects the cingulate cortex at the front of the brain to the cerebellum at the back, passing through the pons region in the brainstem.
For many years, it has been well-documented that the placebo effect is a real phenomenon, especially in the context of pain relief. However, the underlying mechanisms behind the placebo effect have remained a mystery. Now, neuroscientists have made a significant discovery that sheds light on this phenomenon.
Published in Nature, a team of researchers from the University of North Carolina School of Medicine, along with collaborators from Stanford, the Howard Hughes Medical Institute, and the Allen Institute for Brain Science, have uncovered a pain control pathway that connects different regions of the brain.
Through their research, led by Greg Scherrer, PharmD, PhD, the team found that specific neurons and synapses along this pathway become highly active when mice anticipate and experience pain relief, even without the use of any medication.
According to Scherrer, the communication between neurons in the cerebral cortex, the pons, and the cerebellum to adjust pain thresholds based on our expectations is a surprising and promising discovery. This finding raises the possibility of utilizing this pathway for therapeutic purposes, such as using drugs or neurostimulation techniques to manage pain.
The researchers believe that their work provides a new framework for studying the brain pathways involved in other mind-body interactions and placebo effects beyond pain relief.
The Power of Placebos
When faced with pain, the human brain has a natural inclination to seek relief, a behavior that has evolved over millennia. This can lead to the release of chemicals that contribute to feeling better. Positive thinking, prayer, and the placebo effect, where individuals experience relief despite not receiving actual treatment, have been widely documented over the years.
In clinical studies, the placebo effect often manifests in a group receiving a sham treatment, where individuals unknowingly receive a fake intervention. Despite the treatment being inert, some participants still report a significant improvement in their symptoms, highlighting the brain’s ability to influence feelings of well-being.
Understanding the mechanisms behind the placebo effect is crucial for differentiating true treatment effects from the placebo response in research studies. This insight can help scientists develop more effective interventions for various conditions.
Insights from the Scherrer Lab
The team behind the Nature paper recognized that previous studies on placebo analgesia focused on brain imaging, lacking detailed insights into the underlying biology. To address this gap, Scherrer’s team conducted a series of experiments focusing on the anterior cingulate cortex (ACC) to understand the precise mechanisms involved in the placebo effect.
Using a combination of techniques, including genetic tagging, calcium imaging, RNA sequencing, electrophysiological recordings, and optogenetics, the researchers delved into the neurobiology of the placebo effect at the level of individual neurons and synapses throughout the brain.
Their findings revealed that when mice anticipated pain relief, neurons in the ACC sent signals to the pontine nucleus, a previously unrecognized player in pain modulation. Inhibiting this pathway disrupted placebo analgesia, while activating it led to pain relief.
Additionally, the team observed that Purkinje cells in the cerebellum showed similar activity patterns to ACC neurons during pain relief, providing evidence of the cerebellum’s involvement in cognitive pain modulation.
Scherrer envisions that targeting this neural pain pathway could offer novel and effective approaches for managing chronic pain without the side effects associated with traditional treatments.
This research was supported by various funding sources, including grants from the National Institutes of Health and contributions from academic institutions and foundations.
Additional authors involved in the study represented various research institutions and organizations, contributing to the multidisciplinary nature of the research.
