Researchers from University of California in San Francisco (UCSF) identified biomarkers for chronic pain severity using direct brain imaging of chronic pain patients in natural settings. A study published in the journal Nature Neuroscience identified the orbitofrontal cortex (OFC) as an area of the brain directly involved in chronic pain.
What makes this study important for the brain-chronic pain connection
This is the first time anyone has identified the orbitofrontal cortex as a mechanism for chronic pain. However, this study is still “pioneering” in some ways – it is also the first time someone has measured chronic pain directly from brain cells in patients who were observed in their daily life and activities over several months, the study authors wrote.
Previous studies were based on measuring chronic pain in patients under laboratory conditions. They mainly used diagnostic tools such as functional MRI, which provides only four to five images of the current state of pain. As such, this method has a limited ability to understand how chronic pain occurs in everyday circumstances.
Chronic pain and all its aspects: How the brain sees it
By continuously collecting intracranial brain scans and symptom reports collected from patients over months of follow-up, the researchers were able to record the range of pain fluctuations that chronic pain patients experience on a daily basis.
– We know that patients living with chronic pain have good and bad days and that amplitudes happen. This study virtually represents the highest spatial and temporal resolution decoding of neural activity for chronic pain ever performed – said the main author of the study, Dr. Prasad Shirwalkar, associate professor of neurosurgery, anesthesiology and perioperative care and lecturer of pain medicine at University of California.
By identifying the involvement of the OFC in chronic pain, the study also demonstrated the importance of targeting non-somatosensory circuits rather than just somatosensory pathways.
– Our conclusions show that other aspects of pain are just as important as its physical aspect, which has been the focus of research so far. – said Dr. Shirwalkar.
Details of a study that shed new light on the connection of certain parts of the brain to chronic pain
The researchers hypothesized that neural activity from the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), two non-somatosensory brain regions. They are not often studied in relation to pain, and contain an integrated biomarker with the impulse to experience chronic pain. They based the hypothesis on evidence that these brain areas may influence how pain is perceived given their involvement in a functional pain network similar to other brain areas (amygdala insula, ventral layer).
The study included participants with chronic, refractory neuropathic pain, including central post-stroke pain or phantom limb pain. All received a new bidirectional brain implant in both cortices, which allowed pain reports and intracranial imaging to be collected over a period of three to six months. After implantation, participants reported pain multiple times per day during daily functioning.
Brain biomarkers of chronic pain were found to show persistent changes in neuronal activity from the OFC, while the ACC was more associated with acute pain.
Mechanisms of acute and chronic pain through examination of the cerebral cortex
Dr. Prasad Shirwalkar said these findings provide direct evidence that chronic pain and acute pain have different mechanisms related to the brain itself. He added that the study is proof of the claim that objective biomarkers of chronic pain can be obtained in everyday life and the environment.
A planned phase 2 trial will test deep brain stimulation targeting the OFC in 20 to 30 patients with chronic pain. This study of pain mechanisms will be followed in the next two to three years, announced the leading expert of the study.
Other scholars on the study’s merits and demerits
Dr. John Markman, Chief of the Pain Department and Director of the Translational Pain Research Program at the University of Rochester, notes that the research methods used to localize modulation of chronic pain intensity in the OFC cortex are novel. If the findings are verified, they may show the OFC as a new neural target for implanted stimulation approaches to treat chronic pain, the researcher concluded, adding:
“A device that transmits neural waves to this region of the brain could be tuned to modulate neural activity and thus affect the experience of chronic pain,” said Dr. Markman.
However, the scientist noted that the findings based on such a small sample size are still preliminary. According to him, neuromodulation has yet to be confirmed as an effective mode of control and leveling of chronic pain in a larger number of studies, but also how it affects the brain.