Funded Projects

Opioid use during pregnancy is associated with adverse outcomes for pregnant individuals and offspring. The mechanisms through which these outcomes arise and the consequences of prenatal opioid exposure on child health and development remain largely unexplored. The HEALthy Brain and Child Development (HBCD) Study is a nationwide longitudinal prospective study of early child development that will assess a broad spectrum of biological, behavioral, social, and health factors among 7,500 pregnant women and their children from pregnancy to mid-childhood. This supplement will expand the biospecimen collection of the HBCD protocol at the University of North Carolina at Chapel Hill to include delivery specimens (placenta, cord tissue, and cord blood). This will provide an unprecedented resource-generating opportunity for the larger scientific community to comprehensively evaluate mechanisms that mediate the connection between substance use during pregnancy and adverse neonatal, infant, and/or maternal health outcomes and inform innovative preventive strategies.

Emergency departments (EDs) are key settings for identifying and treating opioid use disorder (OUD), but EDs are underused for this purpose. This project aims to develop a data system that automates and integrates electronic health record and administrative data from EDs into the Clinical Emergency Department Registry, partnering with the American College of Emergency Physicians. The research will assess the digital readiness of ED systems before developing and deploying the enhanced ED OUD data infrastructure. This research aims to guide near-real time hospital quality improvement initiatives, toward development of a web-based, near-real time dashboard that can be used in EDs across the country.

Pelvic pain (PP) includes more than 20 different painful and debilitating conditions, such as urinary tract infections, menstrual cramps, endometriosis, overactive bladder, and interstitial cystitis, and affects millions of people. Globally, pelvic pain affects 1 in 5 women and 1 in 12 men. This project will develop an instrument to monitor and treat pain-associated temperature changes in the pelvic region to reduce chronic pelvic pain. This novel system is intended to be used at home with personalized settings.

Chronic post-traumatic headache (PTH) is highly debilitating, poorly understood, and difficult to treat. This project aims to identify proteins located in the membrane of certain neurons that are critical for the development, maintenance, and/or resolution of PTH. These proteins may be targets for novel treatment approaches that are nonaddictive and have minimal side effects.

Decreasing opioid dosing faster than advised by clinical recommendations often leaves chronic pain unaddressed and may increase the risk of overdose and suicide compared to continuing long-term opioid treatment. The MIRHIQL Resource Center will provide infrastructure support for the network as well as create a risk-benefit decision tool to help providers determine when opioids should be continued as prescribed, tapered, or tapered/discontinued. The center will first develop and validate a clinical definition for individuals who take long-term opioids, then study long-term outcomes in participants who receive treatment in primary care settings. This research will partner with many groups including individuals with lived experience, community health care providers who treat such individuals, research scientists, bioethicists, and professional societies

Opioid use during pregnancy is associated with harmful health outcomes for infants including preterm birth, neonatal opioid withdrawal syndrome, and brain-related problems. This project will carry out an in-depth investigation of the effects of opioid use during pregnancy including changes to health of the placenta, inflammation in the fetus, as well as behavioral and movement-related outcomes during the first year of life. This research will contribute to fundamental knowledge about how the placenta and brain work together as well as identify new strategies for diagnosing, treating, and preventing opioid harm to the fetus and mother.   

There is an urgent need for longer acting opioid overdose reversal medications to treat acute fentanyl intoxication and overdose. This project will develop a novel molecule (CS-1103) that sticks to fentanyl and removes it from the body. Previous research with animal models shows that CS-1103 has several features that make it attractive for a new medication. It can reverse fentanyl-induced respiratory depression, preventing another overdose; work in combination with naloxone; and appears to be safe and well-tolerated. The research will continue exploration of CS-1103 toward testing CS-1103 in human research participants.

Physical therapy is the recommended treatment for patients with low back pain and is a cost-effective method for improving pain and reducing disability. However, only 7-13% of patients receive physical therapy services. Access is particularly limited in rural communities due to lack of provider availability, transportation, and missed work time. These factors have contributed to more low back pain-related disability and opioid use among rural populations. Physical therapy delivered through telemedicine may improve access by reducing patient-reported barriers. This randomized clinical trial will compare an innovative, patient-centered telemedicine version of physical therapy to a currently used psychologically based educational approach for rural patients with chronic low back pain. The research will match individual patients to a treatment approach based on their psychosocial risk of poor outcomes.

Neuropathic pain is a debilitating and complex medical condition for which safe and non-addictive treatment options are urgently needed. This project aims to develop new strategies for treating neuropathic pain by controlling the activity of transmembrane protein 97 (TMEM97), also known as the sigma 2 receptor, which has been shown to relieve pain in an animal model of neuropathic pain. The research aims to develop a new molecule that increases TMEM97 activity and is safe for human use, toward obtaining approval from the U.S. Food and Drug Administration for Phase I clinical testing. 

Osteoarthritis is one of the most common joint diseases affecting Americans. Osteoarthritis is particularly high among veterans with a service-related disability. This project will develop and refine a wireless ultrasound device that increases the penetration of over-the-counter pain medications into the body, which is expected to reduce pain. The research will conduct safety and clinical testing toward commercializing this technology. 

This project provides protected time for training and research activities that are required for an independent scientific career in delivering evidence-based treatments for people with opioid use disorder. The increasing presence of fentanyl in the drug supply creates challenges for the use of buprenorphine, because both patients and physicians want to avoid causing withdrawal. This research will interview both patients and physicians to understand their concerns and experiences and work with them to develop a buprenorphine induction toolkit to help balance the advantages of buprenorphine treatment against concerns about the potential presence of unknown fentanyl. 

Opioid use during pregnancy is associated with adverse outcomes for pregnant individuals and offspring. The mechanisms through which these outcomes arise and the consequences of prenatal opioid exposure on child health and development remain largely unexplored. The HEALthy Brain and Child Development (HBCD) Study is a nationwide longitudinal prospective study of early child development that will assess a broad spectrum of biological, behavioral, social, and health factors among 7,500 pregnant women and their children from pregnancy to mid-childhood. This supplement will expand the biospecimen collection of the HBCD protocol at the University of North Carolina at Chapel Hill to include delivery specimens (placenta, cord tissue, and cord blood). This will provide an unprecedented resource-generating opportunity for the larger scientific community to comprehensively evaluate mechanisms that mediate the connection between substance use during pregnancy and adverse neonatal, infant, and/or maternal health outcomes and inform innovative preventive strategies.

Oral cancer pain is debilitating and difficult to treat, in part because even the most effective available pain remedies are limited by side effects. Opioid-based pain medications have several side effects including dependence and tolerance, in which the body gets used to a medicine so that either more medicine is needed or different medicine is needed. Another side effect is hyperalgesia, in which people taking opioids become more sensitive to certain painful stimuli and may misuse the drugs and risk addiction. This project will evaluate lab-made versions of cannabinoid molecules known to block pain signals in nerve cells, but which cannot enter the brain to cause neurological side effects. The research aims to advance promising versions of the molecules to testing in human research participants.