Peripheral nerve stimulation research for phantom limb pain in amputees.

We took note last year of encouraging developments in peripheral nerve stimulation (PNS), a pain-control technology that sends electrical impulses directly to affected nerves. While PNS is designed to treat all forms of chronic pain, not specifically phantom limb pain, the connection is obvious. Two major initiatives are underway to test the treatment’s potential for alleviating phantom limb pain, and the early returns are pretty hopeful.

PNS operates in much the way a pacemaker does—tiny electrodes are threaded under the skin and pulse rhythmically, drowning out erratic neurological signals. In theory, the system “retrains” the affected nerve endings over time, permanently shutting down the neurological pathways involved in phantom limb pain.

“We want to restore the natural kind of signals, something that the central nervous system is used to receiving from the limb,” says Daniel McDonnall, chief scientific officer of Ripple Neuro. The Utah-based company was recently awarded a $2 million grant to develop PNS technology specifically engineered for amputees.

While multiple studies have shown that PNS relieves chronic pain in general, evidence that applies specifically to amputation-related pain is still pretty thin. But that’s changing. Last year the U.S. Veterans Administration launched a pilot study to track pain in the first year following amputation. In a preliminary report, 75 percent of subjects who were treated with the Sprint PNS system (designed by SPR Therapeutics) experienced substantially less pain than the control group during the first eight weeks after amputation—and that’s a critical time to control pain, according to Denise Lester M.D., the lead investigator on the VA study.

“Those with high [post-operative] pain appear to be at greater risk of developing persistent pain,” Lester says. Implementing PNS immediately after amputation may help short-circuit the establishment of pain-causing neural pathways—in effect, retraining the nerves before they fall into the destructive patterns associated with phantom limb pain. To use Lester’s clinical terminology: “By promoting functional plasticity in response to non-painful sensory input from stimulation, percutaneous PNS therapy may ‘unwind’ [pain-causing] mechanisms, thereby altering the chronic pain state.”

Another key benefit of using PNS in the immediate post-operative period, Lester says, is that pain can delay patients’ ability to get fitted for a prosthesis by weeks or months. Successful pain relief via PNS treatment can enable patients to get fitted as soon as two months after amputation, avoiding periods of extended inactivity that are associated with depression, opioid addiction, and deterioration of overall physical condition.

The results of Lester’s pilot study showed enough promise to justify a larger investigation that may begin as soon as this year at multiple VA sites. We’ll keep you posted.

McDonnall’s study for Ripple LLC has an expansive scope that pushes PNS into new territory. It aims to use peripheral nerve stimulation not only to curtail phantom limb pain but also to provide sensory input from the prosthesis. Under Ripple’s design, sensors mounted on the prosthesis relay information about contact, force, and position through the implantable PNS electrodes directly to the nervous system—in effect, establishing direct communication between the prosthetic limb and the brain.

“For example, there is a particular neuron that tells you when your big toe is tapping in a particular area and in a particular way,” McDonnall says. “That signal travels up your leg to the central nervous system. We’re trying to target those few neurons that send this sensation.”

By simulating familiar neurological patterns that existed prior to amputation, Ripple Neuro’s device would diminish the pull of dysfunctional pathways that cause phantom pain. The research is being funded by the National Institutes of Health’s HEAL Initiative, which describes Ripple’s creation as a “next-generation device.”

While the technology isn’t quite ready for clinical trials, Ripple Neuro hopes those will commence in early 2022. We’ll provide updates as they become available.