New Study Spotlights Brain Region Responsible for Placebo Response in Pain

A Northwestern University-led team of researchers has identified a region in the brain responsible for the ‘placebo effect’ in pain relief, when a fake treatment actually results in substantial reduction of pain.

New Study Spotlights Brain Region Responsible for Placebo Response in Pain

In the study, whole-brain degree count maps, collected before the start of treatment, were used to identify potential brain regional markers for placebo propensity. Group differences in whole-brain maps for degree count (number of connections of any location to the rest of the brain) between placebo responders and non-responders identified four brain regions that differentiated placebo responders from non-responders. The highest significant difference was seen for the right midfrontal gyrus. Abbreviations: r-MFG – right midfrontal gyrus; ACC – anterior cingulate cortex; PCC – posterior cingulate cortex; r-S2/M1 – right secondary somatosensory and primary motor cortex. Image credit: Tétreault P. et al .
In this new study and for the first time, the researchers used functional magnetic resonance imaging (fMRI) combined with a standard clinical trial design to derive an unbiased brain-based neurological marker to predict analgesia associated with placebo treatment in patients with chronic knee osteoarthritis pain.
They showed placebo pill ingestion is associated with a strong analgesia effect, with more than half of the patients reporting significant pain relief.
“We identified and validated that clinical placebo response is predictable from resting-state fMRI brain connectivity,” the authors said.
“This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia.”
“Our results show that clinical placebo pill ingestion shows stronger analgesia than no treatment and is predictable from resting state blood-oxygen-level-dependent fMRI, and right midfrontal gyrus degree count identifies placebo pill responders in one trial and can be validated (95% correct) in the placebo group of a second trial, but not in the active drug treatment group,” they added.
Using drugs to treat patients’ pain has been trial and error, with physicians changing dosage or trying another type of drug if one doesn’t work.
The new technique will allow physicians to see what part of the brain is activated during an individual’s pain and choose the specific drug to target this spot.
“It also will provide more evidence-based measurements. Physicians will be able to measure how the patient’s pain region is affected by the drug,” said lead co-author Prof. Vania Apkarian, from the Northwestern University Feinberg School of Medicine.
“Currently, placebo response is primarily studied in healthy subjects within controlled experimental settings,” said lead co-author Dr. Marwan Baliki, also from the Northwestern University Feinberg School of Medicine.
“While such experiments aid understanding of the biological and behavioral underpinning of placebo response in experimental (applied) pain, they translate poorly to the clinic, where pain is mainly chronic in nature.”
“Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials,” he added.
“If future similar studies can further expand and eventually provide a brain-based predictive best-therapy option for individual patients, it would dramatically decrease unnecessary exposure of patients to ineffective therapies and decrease the duration and magnitude of pain suffering and opioid use,” the researchers said.
The findings were published this month in the journal PLoS Biology .