Study finds durable pain relief at two years with Nalu peripheral nerve stimulation system

A randomized controlled trial of a peripheral nerve stimulation system developed by Nalu Medical found durable and statistically significant improvements in pain relief, function and quality of life at 24 months, according to results published Jan. 23, 2026, in the peer-reviewed journal Chronic Pain & Management.

The study, known as the COMFORT Peripheral Nerve Stimulation (PNS) RCT, evaluated the Nalu Neurostimulation System in patients with chronic intractable neuropathic pain. At two years, 85% of patients in the active treatment and crossover arms were classified as responders, defined as achieving at least a 50% reduction in pain. Average pain reduction across those patients was 67%, consistent with previously published data.

More than a quarter of participants — 28% — were considered high responders, reporting at least an 80% reduction in pain. In addition to pain relief, 74% of subjects experienced a clinically significant improvement in functionality, as measured by the Oswestry Disability Index, while 72% reported a clinically meaningful improvement in quality of life. Nearly all participants, 96%, said they were satisfied with the therapy.

“The 24-month outcomes of the COMFORT RCT confirm what we have seen clinically — that peripheral nerve stimulation therapy with the Nalu Neurostimulation System results in clinically significant improvement in patient symptoms, quality of life, and general well-being,” said Mitch Engle, MD, PhD, lead author of the paper. “These robust results reinforce the efficacy and safety of the Nalu Neurostimulation System with consistent pain relief across multiple anatomical targets at all timepoints, from 3 to 24 months.”

Tom West, president and CEO of Nalu Medical, said the long-term consistency of the data is particularly important for patients with difficult-to-treat pain. “The 24-month outcomes provide further proof that the Nalu Neurostimulation System delivers clinically meaningful and sustained relief in patients with chronic intractable neuropathic pain,” West said. “The consistency of results over the last 24 months, and the reproducible outcomes across a range of nerve targets give confidence that the Nalu Neurostimulation System is an effective PNS solution for localized pain.”

The Nalu Neurostimulation System works by delivering gentle electrical pulses to targeted nerves, interrupting or modulating pain signals before they reach the brain. Unlike traditional implanted neurostimulators, the system uses a miniaturized, battery-free implantable pulse generator that is powered wirelessly by an externally worn therapy disc. Patients and clinicians can adjust therapy settings through a smartphone-based remote control app, allowing for individualized programming without the need for surgical battery replacement.

Nalu Medical, based in Carlsbad, Calif., said the system is designed to be minimally invasive while offering advanced waveforms, extensive programming options and an expected service life of 18 years. The device is FDA-cleared for both peripheral nerve stimulation and spinal cord stimulation indications.

Advances in neuromodulation and peripheral nerve stimulation

The COMFORT trial results come amid rapid innovation in neuromodulation technologies aimed at treating chronic pain while reducing reliance on long-term opioid therapy. Peripheral nerve stimulation, once considered a niche approach, has gained momentum over the past decade as devices have become smaller, more targeted and more adaptable to individual patients.

Earlier generations of neurostimulation systems often relied on larger implanted pulse generators with internal batteries that required replacement surgeries every few years. Newer systems, including battery-free and wirelessly powered implants, are designed to reduce surgical burden and long-term complications while extending device longevity. Miniaturization has also expanded the range of anatomical targets that can be treated, allowing clinicians to address localized pain conditions that were previously difficult to manage.

Advances in software and waveform design have played an equally important role. Modern systems offer multiple stimulation patterns and fine-tuned programming options, enabling clinicians to tailor therapy as a patient’s condition evolves. Smartphone-based controls and remote programming capabilities have improved patient engagement and made follow-up care more efficient, particularly for patients with mobility limitations.

Clinical evidence supporting neuromodulation has also grown. Recent studies have shown benefits not only in pain reduction, but also in functional outcomes, sleep quality and overall quality of life. Researchers are increasingly emphasizing long-term data, such as 24-month and beyond follow-up, to demonstrate durability — a key concern for payers, clinicians and patients alike.

Regulatory and reimbursement landscapes have begun to reflect these advances, with broader FDA clearances and increasing payer interest in nonpharmacologic pain treatments. As healthcare systems continue to focus on multimodal pain management strategies, experts say peripheral nerve stimulation is likely to play a larger role, particularly for patients with chronic neuropathic pain who have exhausted conservative therapies.

Together, longer-term clinical data and continued technological refinement are helping to move neuromodulation from a last-resort option toward a more mainstream component of chronic pain care.