A Breakthrough In Chronic Pain Detection?

Recently, a group of researchers at the University of California, San Francisco, reported that they may have found the holy grail of pain management. They accomplished this by performing “the first-in-human, long-term direct brain measurement of chronic pain-related neural activity.”

Physicians have long sought a reliable way to detect and track the presence of chronic pain and its response to treatment but have failed completely so far. Old tropes like pupil size, blood pressure, heart rate, affect, etc., have proven completely unreliable under scientific scrutiny.

In their article, the authors of the new study start off by describing the substantial suffering and debility caused by chronic pain and acknowledge how refractory it has been to treatment. They also recognize that our current measure of pain level, a self-reported zero to ten scale, is lacking objective confirmation by any other measure. These doctors and scientists wanted to develop something better.

They took four patients with severe refractory neuropathic pain and implanted chronic intracranial electrodes in several areas of the brain that have been related to pain perception by noninvasive measures like EEG and MEG. These areas were specifically the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC). Most of us will remember from our medical school days that the frontal cortex is where executive decision-making takes place, as well as the control of movement, and the cingulate cortex is where emotional processing occurs.

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These two specific areas, the OFC and ACC, seem to play a large role in the brain network called the Emotional Regulation Network. This network helps regulate and modulate emotional responses to stimuli, both internal and external. They also play a key role in the Reward and Decision-Making Network, especially the OFC, while the ACC plays a role in monitoring the outcomes of decisions and adjusting behavior accordingly. Now, these networks are not set in stone and are a fairly new development in our understanding of the human mind, so the names and components can vary between authors and studies.

The ACC is also critical to the perception of pain intensity and is included in what some call the pain processing and perception network. According to the study authors, the participants reported pain metrics that were correlated with ambulatory, direct neural recordings that were made several times daily over several months. By analyzing the recordings in these brain areas, the authors were able to successfully predict the pain severity scores reported by the patients through text messages, just by analyzing the neural activity in the OFC and ACC using machine learning methods.

It turned out that there were distinct sustained power changes from the OFC that could be distinguished from patterns created by transient acute evoked pain states. These evoked states had been performed using transient heat stimuli of varying intensity to different body parts. The OFC activity seemed to be a more consistent predictor of chronic pain level perception than the ACC. This seems to correlate with another study I found interesting. This study used EEG to evaluate the difference in resting state EEGs between people suffering from chronic pain and a control group that did not.

They evaluated 101 patients of both sexes using state-of-the-art analysis of oscillatory brain activity. The recordings were analyzed for brain connectivity and network activity that might correlate with chronic pain perception and work as an objective measure to distinguish those suffering from chronic pain and those who do not. The observed connectivity correlations at 4 to 8 Hz (theta) and at greater than 60 Hz (gamma) frequencies. They also noted global network reorganization at gamma frequencies in frontal brain areas in those suffering from chronic pain. A machine learning algorithm was then able to use these theta and gamma bursts to differentiate between patients and healthy controls based mostly on this frontal lobe activity but not to the statistically significant level that the implanted electrodes were able to record.

These studies open the door to the possibility that in the near future, physicians treating chronic pain might be able to noninvasively record brain activity and correlate it with chronic pain perception levels and also track improvements after therapy and treatments have been administered. But we will need to find something besides surgery-implanted brain probes to do it. This brings us to MEG. EEG, electroencephalography, is not as accurate as MEG, magnetoencephalography.

These two brain wave recording modalities both have excellent temporal resolution, but spatial resolution and sensitivity to cortical activity are much improved with the MEG. The problem is cost and convenience. MEGs use devices called superconducting quantum interference devices or SQUIDS. These sensors are cooled close to absolute zero using liquid helium, just like in an MRI, and are extraordinarily sensitive to the minute magnetic fields produced by electrical current flow in neurons as spikes travel down the axons. Liquid helium must be stored under tremendous pressure at around 4 Kelvin. That is -269C or -452F. That requires some very expensive storage systems. That may soon change, though.

While we are constantly disappointed by announcements of room-temperature superconductors that don’t pan out, there might be another option. I have been exploring the possibility of using rare earth barium copper oxide superconductors, called REBCO, in MEG devices. These are ceramic high-temperature superconductors that can operate at liquid nitrogen temperatures, about 77K/-196C/-320F. That does not seem like much of an improvement, but liquid helium is extremely expensive, while liquid nitrogen can be made at home with relatively inexpensive equipment.

The orbitofrontal cortices are extremely accessible to MEG or even EEG records, while ACC activity is deeper in the brain and harder to record. If we can identify a reliable biomarker of chronic pain level perception with a reasonably priced procedure, we could fundamentally change the practice of pain medicine.

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