Summary/Abstract There are currently no biomarkers or tools capable of objectively measuring pain signals. Historically, pain in humans has been measured using subjective rating scales to determine its presence and severity. In animal models, pain is measured by semi-quantitative assays that rely on the observation of pain behaviors. Though useful, the inherently subjective nature of these measures has hampered both research and treatment efforts. The annual economic burden of chronic pain is estimated to exceed $800 billion in the USA alone, largely because inadequately managed pain requires disproportionately more healthcare resources. Similarly, clinical trials for pain therapies are the most expensive, and have the lowest success rate, of all neurological indications. Difficulty managing chronic pain has led to the opioid epidemic as many individuals turn to prescription painkillers as a means of relief, but often end up becoming addicted and resorting to more potent and dangerous opioids as their tolerance increases. Radiocaine is a novel positron emission tomography (PET) imaging agent that we are developing as a biomarker to address the issues in pain care and therapy development. Our recently published findings in a rodent model of neuropathic pain demonstrate the ability to localize the pain generator rapidly and accurately and objectively measure its signal intensity. Our ultimate goals are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The use of pain imaging biomarker technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations, i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. The proposed study will evaluate Radiocaine in early-stage clinical trials. Successful results will set the stage for applied clinical trials that further develop this promising approach into a useful biomarker for transforming pain care.

Project narrative Voltage-gated sodium channels (NaVs) are centrally involved in pain transmission, including aberrant function and expression levels that cause hyperexcitability and chronic pain. Radiocaine is a positron emission tomography (PET) ligand for NaVs. The goal of this project is to evaluate the clinical utility of Radiocaine PET imaging as response monitoring biomarker for chronic pain.