Development of an Implantable Nerve Neurotechnology for the Study and Treatment of Neuropathic Pain

Neuropathic pain, affecting 7-10% of the population, significantly reduces quality of life. Current treatments often fail due to the challenges in translating findings from animal models to humans. Traditional models rely on controlled environments, hindering accurate assessment. Implantable neurotechnologies offer a solution by recording nerve activity in freely-moving animals, providing more realistic data. However, existing devices struggle with long-term recording and signal classification. Implantable neurotechnologies also show promise for directly treating neuropathic pain but lack specificity, inhibiting normal nerve function.

Recent advancements have led to the development of a nerve implant capable of stable long-term recording and signal velocity determination, addressing previous limitations. This technology promises improved insights into neuropathic pain models and more accurate dysfunction assessment. Additionally, it may pave the way for closed-loop therapeutic neuroprosthetics, optimizing pain relief while preserving normal nerve function.

The aim of this research project was to develop an implantable neurotechnology system for long-term recording of neuropathic pain signals and a computational methodology for their selective identification based on signal velocity. Making use of state-of-the-art implant materials such as parylene C and PEDOT:PSS, and fabrication techniques such as photolithography, we produced a nerve cuff capable of being implanted and recording nerve activity for long periods of time. We tested the ability of these cuffs by implanting them in a rat nerve ligation model of neuropathic pain. When implanted into a ligated sciatic nerve, the cuffs were able to record neural signals relating to the pain developed as a consequence of the ligation. We were able to record and track changes in these nerve signals for two weeks after ligation in awake, freely-moving animals.

We furthermore developed two different analysis strategies which, relying on the deployment of electrodes at different positions along the ligated nerve, could identify the velocity of signals being recorded. The first strategy relied on individual action potential signals being recorded at different positions along the nerve, and the latency tracked to identify their velocity. The second strategy applied a cross-correlation analysis approach to identify latencies at which higher activity was present, without the need to identify or select individual action potentials. Both analysis strategies showed that slow afferent (sensory) nerve signals in the range of 1.0 to 1.5 m/s were significantly increased in animals following nerve ligation, as compared to a sham group which did not receive a ligation. Sensory signals of this velocity correspond to C fibres – a population of nerve axons known to carry pain signals. This increased C fibre activity was seen in both idle animals (spontaneous pain) and when the paw innervated by the sciatic nerve was pressed (evoked pain), under awake conditions.

Our results demonstrate the potential of these developed nerve cuffs as tools for neuropathic pain research, enabling for the first time the recording of nerve signals relating to this condition in freely-moving animals over chronic periods of time, and opening the door to future neurotechnology-driven treatments.

We are currently exploring the application of this technology with other laboratories researching neuropathic pain, and identifying funding opportunities to drive these new projects.

Dr. Alejandro Carnicer-Lombarte