Researchers have identified a new brain circuit involved in the placebo effect, particularly in pain relief.
This phenomenon, where merely anticipating relief can alleviate pain without therapeutic intervention, has long been recognized. However, the underlying biological mechanisms remained poorly understood. The study conducted by Greg Scherrer and Chong Chen at the University of North Carolina (UNC), published in
Nature, reveals a neural circuit connecting the anterior cingulate cortex, brainstem, and cerebellum, playing a central role in this effect.
Illustration image Pixabay
The placebo effect often occurs in clinical trials where some participants, receiving an inactive treatment, experience an improvement in their symptoms. This complicates clinical research as it becomes difficult to distinguish the effects of the actual treatment from those of the placebo. The work of Greg Scherrer's team sheds light by showing precisely what happens in the brain during this experience.
To understand these mechanisms, the researchers first developed a mouse model capable of generating the expectation of pain relief. They then used several experimental methods to study in detail neuronal activity in the anterior cingulate cortex (ACC), a region already associated with the placebo effect. Using techniques such as calcium imaging, single-cell RNA sequencing, and optogenetics, they observed that ACC neurons sent signals to the pontine nucleus, a brainstem region previously not associated with pain modulation.
The study reveals that the anticipation of relief strongly activates this neural pathway, characterized by an abundance of opioid receptors, suggesting a key role in pain modulation. By inhibiting this pathway, researchers disrupted placebo analgesia and lowered pain thresholds. Conversely, activating this pathway in the absence of placebo conditioning provoked pain relief.
The scientists also observed that Purkinje cells in the cerebellum, a type of nerve cell, showed activity similar to that of ACC neurons during the anticipation of relief. This discovery provides cellular-level evidence of the cerebellum's involvement in the cognitive modulation of pain.
These results pave the way for new approaches to treat chronic pain, an area where current therapeutic options are often limited by undesirable side effects or addiction risks. According to Greg Scherrer, these findings could enable targeting this new neural circuit for more effective treatments.
Article author: Cédric DEPOND