Neurofeedback (NFB), a functional brain training technique that has been successfully used in a variety of therapeutic fields, has now been shown to reduce significantly the pain of chemotherapy-induced peripheral neuropathy (CIPN) compared to usual care.
"CIPN has pretty much dumbfounded science to this point, and we thought if we can normalize the brain and that makes a difference for these patients, we'd really be onto something," lead author Sarah Prinsloo, PhD, from the University of Texas MD Anderson Cancer Center, Houston, told Medscape Medical News.
And most of our patients are really excited about this treatment, because we're not adding any drug to their regimen, so we're very hopeful that this will become standard of care for the treatment of CIPN," she added.
The finding comes from the first feasibility study of its kind in the cancer care setting. It was published online March 3 in Cancer.
"Neurofeedback is a safe, portable, complementary to other treatment regimens and relatively inexpensive," the researchers conclude in their article.
"And because pharmaceuticals that treat CIPN may have side effects on their own, it is important to consider treatments that minimize or eliminate additional adverse effects for especially vulnerable populations with already existing comorbidities."
"It's exciting, it's interesting, but it's still preliminary, and results need to be reconfirmed," Charles Loprinzi, MD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.
"But if researchers are able to show the same results in another trial, then I think the technique is probably transferable to other places," he added. Dr Loprinzi is the senior author of an accompanying editorial.
First Feasibility Study
In the study, 30 patients with CIPN were randomly allocated to receive neurofeedback, and another 32 patients received usual care (wait-list control). On study entry, patients had neuropathy of grade 3 or higher, CIPN-related moderate to severe pain, or both. The average age of participants was 62.5 years; the majority were white women.
The average length of time since participants had completed chemotherapy was 25.3 months.
The primary outcome of the study was pain related to CIPN, as assessed by the Brief Pain Inventory (BPI) short form.
Those patients in the neurofeedback arm attended 20 functional brain training sessions given over 10 weeks.
"By the end of the treatment period, the NFB group demonstrated a significantly greater decrease in worst pain, our primary outcome," the study authors report. The mean reduction in BPI score was 2.43 for the neurofeedback group vs 0.09 for the usual-care group (P = .001), an effect size of 0.83, which Dr Prinsloo characterized as "pretty impressive clinically."
Secondary outcomes included average pain, scores for which were again significantly lower in the neurofeedback group, at -2.2 at study endpoint, vs +0.13 points in the usual-care group (P = .001) — an effect size of 0.88. Dr Prinsloo commented that an effect size of 0.80 is considered to be robust.
Scores for pain interference also dropped to a significantly greater extent for the neurofeedback group, by 1.86 at study endpoint, vs 0.02 for the usual-care group, an effect size of 0.66. An effect size of 0.50 is considered to be modest, Dr Prinsloo observed.
From the scores obtained by the Pain Quality Assessment Scale — a 20-item scale that quantifies the quality and intensity of neuropathic pain — the neurofeedback group experienced significant improvements relative to the usual-care group in virtually all domains, including unpleasantness. The scores for unpleasantness for the neurofeedback group dropped by 3.27 vs 0.65 for the usual-care group, for an effect size of 1.17, the study authors note.
The investigators also observed that changes in brain activity, as detected by electroencephalography, predicted improvement in CIPN symptoms.
Nonconscious Learning
Dr Prinsloo explained in an interview that neurofeedback is based on the principle of nonconscious learning — learning that occurs when people are not paying attention to the task at hand but the brain is still changing.
"We put electrodes on the patients' scalp and we monitor their brain activity. When patients randomly do what we want they them to do, we put a pretty picture on the screen and an auditory beep goes off, and with repetition, that's how the brain learns. It's basically a reward system," she said.
Currently, neurofeedback sessions must be conducted by a neurofeedback therapist, and other cancer centers are probably not set up to offer the same functional brain training for CIPN patients, Dr Prinsloo noted.
However, with advances in technology, there is reason to hope that neurofeedback sessions could be offered to other CIPN patients, she suggested.
Dr Prinsloo and colleagues are currently running a second trial at the MD Anderson Cancer Center in which the same modality will be evaluated in comparison with placebo, in which patients receive a sham intervention.
Modest Effect
Commenting in an interview with Medscape Medical News, Dr Loprinzi noted that the American Society of Clinical Oncology recommends the use of duloxetine (Cymbalta, Lilly) as a potential treatment for CIPN, but as both he and the study authors emphasize, the benefit of duloxetine in CIPN is modest at best.
"Duloxetine also has some side effects, so it's not a panacea, and something better needs to be done," Dr Loprinzi conceded.
That may well involve modalities such as neurofeedback that appear to be able to modify central processing pathways.
"When you give neurotoxic chemotherapy, it causes damage to the peripheral nerves, so you do a biopsy, and you can see that they are being destroyed," Dr Loprinzi explained.
Over time, peripheral neuropathy tends to improve, but not for every patient, and for those who develop chronic pain in response to an acute injury, "the problem often gets worse and can affect other regions of the body, and it becomes a central processing problem," he added.
In their editorial, Dr Loprinzi and coauthors note that another approach has shown promise in early studies ― the so-called scrambler therapy, as previously reported by Medscape Medical News.
Scrambler therapy appears to work by changing the central perception of peripherally experienced pain and discomfort, the editorialists note.
"With repetitive sessions, data support the idea that long-term relief of pain/discomfort can be obtained," they add.
Pilot studies are now exploring the use of scrambler therapy for treating CIPN to alleviate not only pain but also the tingling and numbness that contribute to the unpleasantness of CIPN, the editorialist add.
The study was funded by the American Cancer Society, the Rising Tide Foundation, the Hille Foundation, and the National Center for Complementary and Integrative Health. Dr Prinsloo has disclosed no relevant financial relationships. Dr Loprinzi has received personal fees from Cubist Pharmaceuticals, Coronado Biosciences, Mitsubishi Tanabe Pharma, PledPharma, Lpath, and Mundipharma for consultations not directly related to the current article.
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