“The causes of CIPN are interpreted by the brain,” she said at the 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology annual meeting. “Bottom line, if the brain perceives pain, then we can change the perception of the brain, and hypothetically change the brain itself.”
Effective treatment and prevention of CIPN remains a considerable challenge in cancer care. Besides duloxetine, no other drugs or interventions have shown considerable promise.
Dr Prinsloo uses an electroencephalogram (EEG) to image the brains of patients in chronic pain and measure the electrical activity of the brain recorded on the scalp. When shown pleasant stimulus, the brain images of patients with chronic pain remain the same as baseline, whereas healthy controls light up and engage with the environment.
“What we see over time in chronic pain patients is that their brains just don’t react to the environment in the way that they typically should,” she said.
According to Dr Prinsloo, the theory behind her research is that if the brain is capable of modifying itself such that pain becomes chronic, it should also be able to modify itself to gain relief from pain.
How It Works
Noninvasive neuromodulation works by using neurofeedback and transcranial magnetic stimulation to measure brain activity.
To measure brain activity in a patient with neuropathy, Dr Prinsloo uses EEG to take 10 minutes of images with the patient’s eyes open, and 10 minutes with their eyes closed. “I then dump that into a database of thousands of other brains that don’t have neuropathic symptoms, and it gives me some hotspots,” she explained.
What she typically observes in patients with chronic pain is a decrease in alpha waves, the wave the brain goes into to relax itself. “This is sort of like a deep breath for the brain,” she said.
Every millisecond, a healthy brain returns to alpha, but the brains of neuropathic pain patients are essentially “turned on” constantly along the sensory motor strip and the parietal lobes.
“So, we see the brain turned on full force in areas that are important for sensory perception, with no relief,” said Dr Prinsloo.
The second stage of neurofeedback treatment involves designing a personalized brain–computer interface through patient engagement in a nonconscious learning exercise.
The patient watches boats on a computer screen, and when alpha waves are amplified, the boat is sent forward, accompanied by an auditory beep. Meanwhile, a therapist watches the EEG screen to keep the “game” going and to keep the patient within an optimal learning threshold.
“They can think about their grocery list if they want to,” she said. “All they have to do is watch the visual feedback so when they make an amplitude of that alpha wave, we reward them by sending the boat forward.”
Significant Reduction in Symptoms with Neurofeedback
Dr Prinsloo and her colleagues conducted a study to test the ability of patients with cancer to control the brainwaves responsible for neuropathy pain, measured by the Brief Pain Inventory (BPI) scale. A total of 71 patients, the majority with breast cancer, were randomly assigned to EEG neurofeedback or a waitlist over the course of 3 years.
Nonwaitlisted patients were required to complete a minimum of 2 sessions and a maximum of five 45-minute sessions per week, for a total of 20 sessions (Dr Prinsloo noted that neurofeedback is relatively inexpensive compared with other interventions, at approximately $120 per session). Brain changes were examined before and after neurofeedback.
“We had 100% compliance; I think because we had some fairly outstanding results,” she said. “People would come in and say they hadn’t felt their feet in years, and 2 or 3 sessions later, they could feel the bottom of their feet. So, they got really motivated, really early on.”
Patients in the intervention group experienced decreases in worst pain (the primary outcome), intensity, unpleasantness, and numbness. The same trend was seen in long-term impacts such as activity, mood, sleep, and cognitive function, she reported. The waitlist group was then treated, and they also drastically reduced their symptoms. According to Dr Prinsloo, neurofeedback demonstrated a greater reduction in average pain intensity compared with duloxetine.
“It’s all well and good, but unless you can show that you’re actually changing what you want to change, it’s sort of voodoo,” she added. “So, we compared the treatment and control groups, and showed that we changed that ratio between fast-wave and slow-wave activity in the location of the brain we trained, and also reduced the fast-wave activity.”
When patient-reported outcomes were evaluated in conjunction with brain function, they observed that a decrease in fast-wave activity was associated with decreased symptoms.
The researchers then conducted a placebo-controlled clinical trial on patients with breast cancer, and measured unpleasantness as the primary outcome. “I didn’t use BPI as the primary outcome in this study because I learned that some patients don’t have pain,” Dr Prinsloo noted.
The results are not yet published, but according to Dr Prinsloo, neurofeedback demonstrated promising results, with greater effect sizes than placebo in 16 of 19 scales.