Chronic pain is common and a major economic burden. An estimated 100 million people in the US, and 1.5 billion people worldwide, suffer from chronic pain. In the US alone, estimates of the total annual incremental cost of health care due to pain ranges from $560 billion to $635 billion (in 2010). So far, only approximately 1 out of 4 individuals with chronic pain receive appropriate therapy. A significant contributor to poor chronic pain management is misuse of medication (e.g., opioids). Studies have shown that opioid nonadherence rates range from 47% to 78% in chronic pain patients. This proposal aims to develop a wearable and minimally invasive sensing system that will enable remote and continuous monitoring of opioid medication adherence as part of prescribed treatment for chronic pain management. A wearable sensory patch containing microneedles will be developed to continuously monitor opioid levels in the interstitial fluid. The opioid sensor will communicate securely and wirelessly to a system that will aggregate data collected from multiple wearable devices (such as activity monitors and physiological sensors) to estimate the patient physiological and functional state as well as detect overdose and nonadherence events. The proposed project directly aligns with the mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) through the research and development of a new biosensing technique to fundamentally improve the monitoring of opioid-based pain management adherence and early detection of opioid overdose. Also relevant to the NIBIB mission, achieving the aims of this project requires a multi- disciplinary approach and complementary advances in materials science and computer science. From the healthcare perspective, this project will offer evidence-based and personalized decision support to caregivers for better treatment of chronic pain. The long-term impact of improved pain management adherence will lead to better pain control, reduce the economic burden of pain and palliative care, and reduce the deadly side effects of opioid overdose.