SmartStim, a novel implantable neuromodulation system to cure chronic pain. - Project Summary/Abstract Chronic pain without apparent tissue damage is characterized by central sensitization at the level of spinal cord and brain, which often results from prolonged peripheral sensitization of nociceptors, consisting of small-diameter Aδ- and C-fiber afferents with cell bodies in the DRG. Our goal is to develop a novel treatment for chronic pain that provides sustained relief by targeting the root cause: reversing the underlying neural sensitization. The objective is the translational development of a combined device/drug treatment for chronic pain that utilizes a SmartStim device and a long-lasting, safe nerve block reagent to synergistically achieve selective blockage of peripheral nociceptors, especially C-fiber nociceptors. Existing neuromodulation methods, such as spinal cord stimulation, typically mask pain by inducing paresthesia but fail to address the underlying cause, leading to diminishing efficacy over time. The proposed SmartStim system addresses this by offering tunable and selective transmission blockage of sensitized nociceptive afferents through a combination of electrical stimulation and localized drug release at the level of DRGs. Prolonged suppression of peripheral nociceptive drive, especially from C-fiber nociceptors, can potentially engage central plasticity, eventually reversing the disease state of central sensitization. Additionally, the SmartStim system employs similar mechanical design and implantation methods as conventional DRG stimulators and also provides comparable paresthesia-based therapy to suppress pain, making it a safe and significant upgrade over existing DRG stimulators. Three Aims are proposed. Aim 1 will develop an implantable pulse generator (IPG) to deliver two proprietary stimulation protocols for blocking nociceptive afferents. Aim 2 will develop localized NaKA inhibition to enhance the therapeutic effect of DRG stimulation in blocking nociceptive afferent transmission. Aim 3 will develop the prototype of the SmartStim system and conduct system validation. Successful development of SmartStim will lead to a paradigm shift in chronic pain management, offering a mechanism-based and sustainable treatment option for patients who have not found relief with existing therapies.
