A new study has reported that intracranial orbitofrontal cortex (OFC) signals can be used to predict spontaneous, chronic pain state in patients. The OFC is an area typically involved in emotion regulation, self-evaluation, and decision-making.
Approximately 1 in 5 adults in the United States suffers from chronic pain, a condition described as persistent or recurrent pain that lasts longer than 3 months.
Measurement and accuracy of the degree of pain has been inconsistent and typically relies on the clinician asking the patient to assess his or her pain based on a numerical or visual scale. These measures are at best subjective and may have substantial daily variability. Moreover, chronic pain syndromes are often refractory to treatment and can cause substantial suffering and disability with loss of work and an inability to manage daily activities.
To date, objective biomarkers that could be used to guide diagnosis and treatment have not been defined. In addition, there is a paucity of knowledge as to which brain activity might underlie chronic pain on clinically relevant timescales, and even how cerebral activity may relate to acute pain.
In this study, chronic intracranial electrodes were implanted in the anterior cingulate cortex and orbitofrontal cortex (OFC) in 4 patients with refractory neuropathic pain. In 3 of the patients, pain had started after a stroke and the fourth patient had phantom limb pain after a leg amputation.
Participants then reported pain metrics coincident with ambulatory, direct neural recordings obtained multiple times daily over months. The researchers were able to successfully predict intraindividual chronic pain severity scores from neural activity with high sensitivity using machine-learning methods, which could then point to high and low chronic pain states based on brain signals alone. Chronic pain decoding relied on sustained power changes from the OFC, which tended to differ from transient patterns of activity associated with acute, evoked pain states during a task. Each patient showed unique brain activity, rather like the individuality seen in fingerprints.
The authors conclude that intracranial OFC signals can be used to predict spontaneous, chronic pain state in patients. Although this study is very small, it does add to the information that has already been obtained from deep brain stimulation for movement disorders and Parkinson disease and such diverse situations as overeating and obesity.
It is possible, with further research, that other areas of the brain may be involved in pain states. However, although it is early to say, such patterns of brain activity could serve as biomarkers to guide diagnosis and treatment for millions of people with shooting or burning chronic pain linked to a damaged nervous system. (See Shirvalkar P, Prosky J, Chin G, et al. First-in-human prediction of chronic pain state using intracranial neural biomarkers. Nat Neurosci. 2023;26(6):1090-1099. doi:10.1038/s41593-023-01338-z.)