Project Summary/Abstract: The most common noticeable symptom of disease and injury is pain. It can warn of danger or the need to treat a problem, however, when it becomes chronic, it can become debilitating. Chronic pain is estimated to affect up to a third of the global adult population(Majeed et al., 2018). Complications from pain treatment continue to cause addiction and injury (including death). Alternative methods for treating chronic pain (especially that recalcitrant to treatment) is critical to addressing both chronic pain itself and mitigating the hazards of long-term administration of current treatment methods. As is seen in the ongoing opioid crisis and the massive costs of chronic pain treatments, the consequences of untreated pain and treatment that lacks specificity can be dire. This results in a loss of quality of life and productivity. Optogenetics offers the possibility for both highly specific and customizable control of cellular activities, opening pathways for treatments that reduce risks via cellular specificity while also allowing personalized therapies. Currently, the most common opsins require an excessive amount of power to be activated or are sensitive to wavelengths of light that can damage tissues, thus limiting their utility in medical treatments. To address these limitations, we have developed a unique sensitive opsin and a stimulation device which can provide targeted and tailored activation of the opsin. Multi- Characteristic Opsin (MCO) can be delivered to neurons involved in the sensation and processing of pain and stimulated as needed to minimize pain perception. Preliminary research has established the baseline parameters for optogenetic modulation of pain, and our continued research establishes the value and safety of this approach for pain management. To further the characterization and optimization of our approach, we plan to perform the following aims: Aim 1: Optimize OPM optical delivery and transdermal/wireless optogenetic stimulation device. Aim 2: Optimize the efficacy of the Modulator and Opsin construct for safe long-term treatment of pain. Successful development holds the promise to revolutionize pain therapy through a highly specific, personalized approach to pain mitigation with reduced hazards and enhanced rewards. This novel optogenetic treatment could be applied to several chronic pain syndromes with potential applications for other neurological conditions.

Project Narrative (3 sentences): Cell specific and customizable treatments for chronic pain are essential for addressing this global health challenge and its related adverse consequences. Here we outline a virus-free method to sensitize cells in the spinal cord to the the uniquely sensitive and potent Multi Characteristic Opsin (MCO) as well as the compact and transdermal Optogenetic Pain Modulator (OPM) device to treat pain. Successful development of this therapy will enable the production of a clinically viable product that could treat chronic pain in a safe, effective, and personalized manner.