A team of Brown University researchers has developed and patented a new, objective measure of pain using a noninvasive electroencephalograph of theta-band brain waves, which is designed to help doctors better diagnose and manage pain, helping to prevent opioid addiction.
Researcher Carl Saab, an associate professor of neuroscience and neurosurgery at Brown University and Rhode Island Hospital, said patients only get about 20 minutes to describe what is often a yearslong struggle with pain to doctors. The time limit doesn’t allow for the patient to describe what kind of pain they’re in or how severe it is. That makes it difficult for doctors to determine what pain medication to prescribe, and how much, he said.
Saab is senior author of “An Electroencephalography Bioassay for Preclinical Testing of Analgesic Efficacy,” a paper published in Scientific Reports on Nov. 6.
“I felt that the pressure point in the system is more on the diagnostic side,” Saab said.
So, five years ago, he and his team began looking for a way to measure whether animals are feeling pain.
The current method to measure pain, and the effectiveness of potential pain medications, in a preclinical animal model is to poke the animal’s paw and see how quickly it moves its paw away. Slow paw withdrawal is linked to less pain and better pain medication. Faster paw withdrawal is linked to more pain and less-effective pain medication.
“When I was a graduate student, I hated this test because it had nothing to do with clinical pain,” said Saab, who is affiliated with Brown’s Carney Institute for Brain Science.
‘It could be part of a solution that would be more humane for patients.’
DR. KEVIN BAILL, Butler Hospital psychiatry unit chief
Saab said the EEG-based test is a more direct measure of ongoing, spontaneous pain than the current approach and could help researchers develop more-effective medications for chronic back pain or sciatica, conditions that don’t have many effective treatments.
In the paper, Saab’s team looked at three pain medications and compared their effectiveness in an animal model of sciatica. The researchers used the traditional behavior test, the EEG test and an analysis to determine blood concentration of the medications, which was compared to the clinical blood concentration of the medications in human patients.
The first medication they tested was a proven treatment for some forms of chronic pain, sold under the brand name Lyrica. The second was a promising pain medication in phase two clinical trials, and the third was a medication with inconclusive effectiveness in earlier studies.
Overall, the theta-wave measurement and behavior test gave similar results, said Saab.
In some experiments, the EEG test showed a decrease in theta power measurement at the clinical dose but not the low dose, while the behavior test showed slower paw withdrawal at the low dose and the clinical dose, resulting in a false positive.
“The ability to detect false-positive or false-negative outcomes is crucial to the drug-development process,” the authors of the paper wrote. Saab believes the EEG test can aid researchers in identifying false positives in preclinical trials of new pain medications, improving the development process.
To develop the EEG test into an objective pain-measurement tool, Saab is working to calibrate the EEG signatures of pain with the traditional smiley face-based, pain-assessment tool: a row of numbered faces, with expressions from a smile to a grimace, used to indicate pain severity.
That kind of pain measurement has been discredited, said Dr. Kevin Baill, chief of the psychiatry unit at Butler Hospital, which was named a Center of Excellence for opioid-addiction treatment in December 2017.
“It’s not as easy as it sounds to take a feeling that you have and give it a number,” Baill said.
But Saab’s work stands to make such assessments more objective.
“It’s just a matter of reading brain activity and matching it to a pain report,” Saab said. His goals for the test were for it to be quick and noninvasive, so a patient could be in and assessed within three minutes, and low-cost so that it wouldn’t create a health disparity.
So far, he said, the theta-wave readings can be used to determine if someone is feeling pain, “But we won’t be able to tell pain severity.” That level of measurement will likely take another three to five years, he said.
The approach could aid in developing more-effective pain medications and improving the diagnosis and management of chronic pain, both contributing factors to the opioid epidemic, Saab said.
Saab said he founded Neurotecnix Inc. about four years ago and has since filed several patents stemming from his pain-measurement research.
An objective measure of pain would be a big help in diagnosis, Baill said, adding pain is a difficult feeling to measure.
“There are all sorts of things that can make a person experience more pain than another person,” he said.
With an objective measure of the pain a person is experiencing, “I think that would be kind of revolutionary,” Baill said. He said that with an approach to pain management that combined medication with physical therapy, acupuncture, yoga and other alternative treatments, Saab’s pain measurement could be used to find what works best for each patient.
“I certainly think that it could be part of a solution that would be more humane for patients,” Baill said.
Rob Borkowski is a PBN staff writer. Email him at Borkowski@PBN.com.
