Regenerative Peripheral Nerve Interface: Prosthetic Control to Neuroma Pain Relief

Researchers at the University of Michigan made headlines in 2020 when their regenerative peripheral nerve interface (RPNI) allowed amputees to control their prosthesis with their mind. But through their countless testing and trials, they also discovered that this innovative procedure could provide patients with neuroma pain relief as well.

First developed at the University of Michigan in 2012, RPNI is now considered the standard of care for neuroma pain relief in their Section of Plastic Surgery, and surgeons have since treated neuroma pain in over 250 amputees to date.

Here’s how researchers recognized the need for new technology for prosthetic limbs, how RPNI was tested and developed, and the surprising discovery that paved the way for neuroma pain relief and prevention for patients.

2012: Addressing the Need for a Change

Recognizing that amputees seemed to prefer prosthetics that could be operated with their own body rather than with advanced new technology for prosthetic limbs, Urbanchek et al. sought to create an RPNI that had similar peripheral nerve signaling capacities as Sham devices.

Implanting their device into rats’ thighs, they found that the capacities of neurotized RPNI were 50% to 100% of those of Sham devices. They also found that their RPNI was able to trigger reinnervation and revascularization in the rats’ leg.

2016: Improving Signal Quality

Now shifting their focus towards upper limb amputees, Irwin et al. hoped to demonstrate that the RPNI could address issues with signal quality and longevity in similar treatment options that had been used at the time.

They implanted nine RPNIs on the forearms of two monkeys and trained them to perform cued finger movements. Signals recorded from the RPNIs were found to be similar to intact control muscles, and functionally-specific electromyographic (EMG) signals were correlated with the expected finger movements of each nerve branch. Using these signals, the study authors were able to classify each monkey’s finger movements as flexion, extension or rest with over 96% accuracy.

Having the monkeys perform a behavioral task with both their own hand movements and RPNI control, Irwin et al. also noted that the monkeys were equally successful using either method, with no noticeable adjustment period when switching to RPNI control. This further demonstrated the natural, physiologic functional prosthetic control that the RPNI could provide.

2016: Can RPNI Provide Neuroma Pain Relief?

Through their animal studies, researchers began to realize that there was a noticeable lack of neuroma formation within the regenerative peripheral nerve interface and wondered if it could be used for treatment of symptomatic neuromas in humans. With this in mind, Woo et al. created a pilot study to test the ability of RPNI to provide neuroma pain relief in 16 amputee patients.

Three to 15 months after RPNI surgery, patients in this study reported an average reduction in their neuroma pain score of 71%. Additionally, 75% of patients reported at least a 50% reduction in neuroma pain score after surgery. Woo et al. also found that the RPNI surgery reduced phantom pain as well, with patients reporting an average reduction in pain of 53%.

While the study authors noted that there were some limitations to this study, including that two patients developed new neuroma pain at different sites, and that they only examined a small group of patients with no control group, they ultimately concluded that RPNI can be a simple and effective method of managing postamputation neuroma pain.

2019-Present: What Does the Future of RPNI Hold?

After their pilot study showed promise that RPNI could treat neuromas, researchers wondered if it could help prevent neuromas from forming as well. In their 2019 study published in Plastic and Reconstructive Surgery, Kubiak et al. analyzed 90 patients, half of which had undergone RPNI implantation during their primary limb amputation, and half of which served as the control group, having underwent standard amputation without RPNI.

None of the RPNI patients developed symptomatic neuromas during the study period, while six of the control patients did. Additionally, only half of the patients with major limbs amputated had phantom pain postoperatively.

Some limitations of the study, the authors noted, were that neuroma pain isn’t a widely known condition among amputees, and therefore patients may have not accurately reported it, and given that pain is a subjective experience, it may be reported and interpreted differently among each patient.

However, the study did demonstrate that prophylactic RPNI is associated with reduced symptomatic neuroma formation, and further research, Kubiak et al. noted, would be needed to better understand and characterize its ability to do so.

Later, in their 2022 paper on RPNI titled “Decreasing Postamputation Pain with the Regenerative Peripheral Nerve Interface (RPNI),” Kubiak et al. acknowledge that their 2019 study, along with several others conducted at the University of Michigan, had demonstrated that RPNI can be successfully used for neuroma pain relief and prevention.

They note that surgeons from multiple subspecialties are now incorporating RPNI into their amputation procedures and have found that any patient that can heal from surgical wounds from limb amputation can also be expected to heal from RPNI surgery. This includes patients with comorbidities such as critical limb ischemia, diabetes and peripheral vascular disease.

While additional studies to further determine the efficacy of RPNI for neuroma pain relief are currently underway, Kubiak et al. are encouraged about its potential to significantly improve outcomes and overall quality of life for amputee patients in the future.