bandaged hand typing on keyboard showing carpal tunnel

One of the biggest mysteries about pain is how (and when) acute, short-term pain turns into a long-lasting, chronic problem. As a complex sensory and emotional experience, chronic pain often involves changes in the brain that convey inappropriate pain signals. For that reason, research funded by the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative® is using a range of strategies to “treat” the brain to relieve chronic pain, such as that caused by carpal tunnel syndrome.

Carpal tunnel syndrome usually begins with numbness or a burning sensation in the hands and fingers – at night or first thing in the morning. The condition is caused by pressure on the median nerve traveling down the arm to the fingers. When this nerve gets squeezed in the carpal tunnel, a narrow passageway in the wrist surrounded by bones and ligaments, symptoms occur. It can also cause weakness in the hands, resulting in a tendency to drop things. Most troubling is that in some people, carpal tunnel syndrome becomes a life-altering chronic pain condition that is very difficult to live with.

Targeting Brain Pain

Of the more than 13 million Americans with carpal tunnel syndrome, it is estimated that at least 18% experience debilitating pain that has become “centralized” within the brain – meaning that the brain is creating the perception of pain, even though there are only minor, or even no, physical stimuli that would create it. For these individuals, explains HEAL researcher Laura Dipietro, Ph.D., various treatments including physical therapy, acupuncture, surgery, and medications have not helped. Opioid treatment carries the risk of addiction and doesn’t always relieve the pain.

“Unfortunately,” Dipietro says, “these treatments have limited and/or inconsistent effects, and some have significant side effects.” In addition, she adds, most of these treatments act at the site of pain (the wrist and arm), even though most patients experiencing pain from carpal tunnel syndrome have a brain-based component driving their pain.

Dipietro and Timothy Wagner, Ph.D., of the neurotechnology company Highland Instruments in Wellesley Hills, Massachusetts, are testing non-invasive stimulation applied to the scalp as a way to calm brain-caused pain in people with carpal tunnel syndrome.

“What we’re trying to do is to induce a change, modulate the brain, and affect a patient’s pain in such a way that it can improve their quality of life,” says Wagner. The technology they are using, Electrosonic Stimulation (ESStim™), does not require surgery. Neuromodulation works through a combination of electrical and ultrasound energy, targeting areas of the brain (through the scalp) that process pain. The process can act like an electrical switch to turn up or down nerve activity – with the intent to decrease pain signals.

Everyone’s brain is different, so the team has used electroencephalogram (EEG) recordings and magnetic resonance imaging (MRI) to figure out exactly where to stimulate a patient’s scalp based on that individual’s brain activity. The scientists apply stimulation for 20 minutes using a soft, moist pad and an ultrasonic transducer placed directly on a patient’s head. The process is not painful, and patients are awake during the procedure.

During the first phase of this research, Dipietro explains, the team treated 20 people with carpal tunnel pain: half received electrical/ultrasound stimulation and half received stimulation that has no effect on brain activity but feels the same as the actual stimulation. This way, patients don’t know which treatment they received, which could have unintentionally affected their responses.

Results from this initial study are exciting: patients receiving the treatment reported less pain, along with improvements in the ability to use their hands. A second phase of the research, including more patients, will test whether physical therapy adds even more relief.

“The idea of personalized medicine when it comes to non-invasive brain stimulation is a big area of interest to us,” Wagner explains, adding that optimizing the dose based on an individual’s brain and pain sensation will be the next step.

Technology Solutions for Treating Chronic Pain

Stimulating the brain to treat illness is not new. The method is currently used to treat a wide range of conditions, including spinal cord injury, epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, tinnitus, traumatic brain injury, and others. Highland Instruments is also testing ESStim for treating addiction, and in other research not funded by HEAL. For example, it is being used for patients who have other pain syndromes and also for patients with balance-related issues from Parkinson’s disease.

To date, however, scientists have not been very successful at treating pain this way, but a lot of work is under way. Other HEAL researchers are testing spinal cord stimulation, an “injectable electrode,” and various other types of brain stimulation, including focused ultrasound to the scalp for cancer pain or sickle cell pain. In addition, scientists are testing deep brain stimulation, in which electrodes are implanted into the brain by a neurosurgeon. This approach has been used successfully for Parkinson’s disease, obsessive compulsive disorder, and epilepsy. HEAL research is funding deep brain stimulation treatments for both severe opioid addiction and chronic pain.

One reason it is hard to treat pain is because it is different in every brain. That, explains Wagner, is why patient-specific dosing will be so important. Currently, Wagner and Dipietro are testing their treatment for chronic carpal tunnel syndrome pain using a 20-minute stimulation each day for 10 days.

Pain relief is not immediate, explains Wagner. “We’re not permanently changing the brain or permanently repairing the wrist,” he says, but rather tuning the “abnormal volume control” within the brain.

Ultimately, the team envisions at-home therapy if this approach is effective in larger studies and is approved for use by the U.S. Food and Drug Administration. Patients might be first dosed in a clinic, then apply stimulation at home themselves through a telehealth platform.

In the meantime, technology remains only one solution for treating pain. It is likely that for most people, a combination approach of safe, non-addictive medications, technologies, and psychologically based pain coping skills will be most useful. HEAL research is also untangling the mystery of how and when acute pain turns chronic. Understanding this transition is a major focus for researchers aiming to prevent chronic pain in the first place.

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