USC's new AI implant promises drug-free relief for chronic pain

Current implantable electrical stimulators offer an alternative by stimulating the spinal cord to block pain signals from reaching the brain. But these devices come with drawbacks like high cost, invasive surgery, and the need for frequent battery replacements. Now, researchers from the Zhou Lab in USC Viterbi's Alfred E. Mann Department of Biomedical Engineering, in collaboration with the Jun Chen Group at UCLA, have developed a revolutionary solution: a flexible ultrasound-induced wireless implantable (UIWI) stimulator secured to the spine and designed for personalized, self-adaptive chronic pain management.

This groundbreaking device, detailed in Nature Electronics, represents a significant leap forward in pain therapy. While current spinal cord stimulators can be unwieldy and are hard-wired to batteries, the new device is designed to bend and twist with movement and is powered by a wearable ultrasound transmitter without the need for a battery. It also harnesses machine learning algorithms to customize treatment for each patient. The work was led by Zohrab A. Kaprielian Fellow in Engineering Qifa Zhou, who is also a professor of ophthalmology at the Keck School of Medicine of USC.

Pain Relief on Demand: How the Implantable Stimulator Works

At the heart of this innovation is its wireless power supply, eliminating the need for bulky batteries and complex wired interfaces that often require repeated surgeries. The UIWI stimulator receives its energy from an external, wearable ultrasound transmitter (WUT). Ultrasound offers a safe, effective non-invasive method for deep-tissue penetration. The device converts mechanical waves into electrical signals through a phenomenon called the piezoelectric effect. The core of the UIWI stimulator is a miniaturized piezoelectric element made from lead zirconate titanate (PZT), a highly efficient material for converting incoming ultrasound energy into the electrical power needed for stimulation.

"What truly sets this device apart is its wireless, smart and self-adaptive capability for pain management," Zhou said. "We believe it offers great potential to replace pharmacological schemes and conventional electrical stimulation approaches, aligning with clinical needs for pain mitigation."

Ph.D. candidate in the Zhou Lab and lead author Yushun (Sean) Zeng said the wireless smart miniaturized stimulator had the ability to produce sufficient electrical stimulation intensity by using ultrasound energy, resulting in a more personalized, targeted and localized treatment.

"This energy-converting type is critical for deep stimulation, as ultrasound is a non-invasive and highly penetrating energy in clinical and medical areas," Zeng said. "By leveraging wireless ultrasonic energy transfer and closed-loop feedback system, this UIWI stimulator removes the necessity for bulky implanted batteries and allows for real-time, precisely adjustable pain modulation."

"From a clinical standpoint, incorporating deep learning-based pain assessment enables dynamic interpretation and response to fluctuating pain states, which is essential for accommodating patient-specific variability." added Zhou Lab Ph.D. candidate Chen Gong, also a lead author on the paper.

The device works by:

Detecting pain: The system continuously monitors brain recordings, specifically electroencephalogram (EEG) signals, which reflect a patient's pain levels. Harnessing AI to assess pain levels: A sophisticated machine learning model, based on a neural network called ResNet-18, analyzes these brain signals and classifies pain into three distinct levels: slight pain, moderate pain, and extreme pain. This AI model boasts a 94.8% overall accuracy in distinguishing between these pain states. Adapting treatment as needed: Once a pain level is identified, the wearable ultrasound transmitter automatically adjusts the acoustic energy it transmits. The UIWI stimulator can then sense the propagated energy and convert it into electrical intensity, stimulating the spinal cord. This creates a closed-loop system that provides real-time, personalized pain management. The UIWI stimulator itself is flexible, bendable, and twistable, allowing for optimal placement on the spinal cord. The electrical stimulation it provides to the spinal cord works by rebalancing the signals that transmit and inhibit pain, effectively suppressing the sensation of pain.

Demonstrated Success in the Lab The Zhou Lab team tested the UIWI stimulator in rodent models, with results demonstrating its effectiveness for pain management.

Researchers successfully relieved chronic neuropathic pain caused by both mechanical stimuli (like a pin prick) and acute thermal stimuli (infrared heat).

Lab tests showed that treatment from the UIWI stimulator led to significant reductions in pain indicators. In one experiment to evaluate whether an animal associates an environment with pain relief, rodents showed a clear preference for the chamber where the pain management system was activated, further confirming the device's effectiveness.

The Future of Personalized Pain Relief

The successful development and testing of the UIWI stimulator mark a pivotal moment in the quest for advanced pain management. The flexible design of the implant and its integration with sophisticated AI algorithms offer a dynamic and personalized treatment approach that can adapt to the fluctuating and highly individual nature of chronic pain.

Looking ahead, Zhou and his collaborators are hoping for even more advanced applications of the device. Zhou said that future designs could miniaturize the components further, enabling less invasive device implantation -- for instance, with a syringe. The wearable ultrasound transmitter could also evolve into an untethered, miniaturized device or even a wearable ultrasound array patch, potentially combining imaging capabilities with energy delivery for real-time monitoring and targeted stimulation. Future iterations could also be controlled by smartphone software, offering even more robust personalized pain management.

Zhou said the aim of the device was to transform chronic pain management, moving beyond the limitations of current solutions to offer a truly personalized, intelligent, and effective pathway to pain relief.

"Our findings highlight the potential of ultrasonic implantable electronics in clinical and translational chronic pain management," Zeng said.