Funded Projects

It is unclear if long-term use of opioids by head and neck cancer patients affects risk for depression, which is higher in this population compared to people without cancer. This knowledge could inform interventions such as increased opioid prescription safety or alternative pain management approaches and could thus help reduce the risk for depression-related outcomes. This project will use data from a national cancer database linked to Medicare claims and a Veterans Administration database to determine whether people with head and neck cancer that take opioid medications for more than 90 days have increased risk for new-onset or worsening depression or suicide death.

A more than 5-fold increase in the incidence of neonatal abstinence syndrome has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment. Five institutions (Duke University, Arkansas Children’s Research Institute, Cincinnati Children’s Hospital, University of Illinois at Urbana–Champaign, and University of North Carolina at Chapel Hill) have formed a consortium to develop strategies for the Phase II HEALthy Brain and Child Development Study. Research teams will develop instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools); conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments; and analyze available data, including imaging, behavioral, cognitive, and maternal data from studies on early brain development, to guide the Phase II study design. Upon completion, the consortium aims to conduct the Phase II study.

Given the magnitude of the opioid death epidemic, we need multiple approaches to increase use of medication treatment for opioid use disorder (MOUD) for people from diverse geographical locations. Pharmacists as dispensers of and gatekeepers to opioid medications, including those used for OUD treatment, are natural partners of health care providers. Community pharmacists are widely available even in rural areas. This 2-year study will use a mixed-method design that includes qualitative and quantitative approaches to study pharmacists’ knowledge of, attitudes about, and intention to provide patient care and services for screening, brief intervention, and referral to treatment for substance use disorders and MOUD. Study aims are to conduct stakeholder interviews, develop a survey instrument to assess such barriers and facilitators, pilot test the survey instrument, and conduct the survey among licensed pharmacists.

This project will design and test optimized temporal patterns of stimulation to improve the efficacy of commercially available spinal cord stimulation (SCS) systems to treat chronic neuropathic pain. Researchers will build upon a validated biophysical model of the effects of SCS on sensory signal processing in neurons within the dorsal horn of the spinal cord to better understand how to improve the electrical stimulus patterns applied to the spinal cord. They will use sensitivity analyses to determine the robustness of stimulation patterns to variations in electrode positioning, selectivity of stimulation, and biophysical properties of the dorsal horn neural network. Researchers will demonstrate improvements from these new stimulus patterns by 1) measuring their effects on pain-related behavioral outcomes in a rat model of chronic neuropathic pain and by 2) quantifying the effects of optimized temporal patterns on spinal cord neuron activity. The outcome will be mechanistically derived and validated stimulus patterns that are significantly more efficacious than the phenomenologically derived standard of care patterns; these patterns could be implemented with either a software update or minor hardware modifications to existing SCS products.

Improved pain management and reduction of opioid use could greatly benefit from improved pragmatic clinical trials (PCTs). The PRISM Resource Coordinating Center (CC), as part of the NIH Health Care Systems Research Collaboratory, will support up to nine more embedded PCTs that address pain management and the opioid crisis. Since 2012, the CC has nurtured 15 Demonstration Projects by providing leadership, resources, tools, training, and coordination of diverse elements. The CC will work collaboratively with each PRISM Demonstration Project team supported through the HEAL Initiative, including their partnering health care systems, to develop, test, and implement the projects while providing technical, design, and coordination support. The CC will also develop and refine technical and policy guidelines and best practices for the effective conduct of pain-related research studies in partnership with health care systems and disseminate best strategies for successful embedded PCTs.

Exposure to opioid analgesics during medical care is a key driver of the opioid epidemic. Such exposures are widespread. Yet opioids remain essential first-line agents in treating pain, and it remains vital that pain be appropriately managed. Non-opioid pain treatments help to resolve the opioid/pain conflict. This project will examine the opioid-sparing and pain-relieving potential of a novel, non-pharmacological treatment for pain, using the effects of green light exposure to reduce pain and thereby reduce the quantity of opioids needed for pain relief.

Rates of neonatal abstinence syndrome (NAS) have skyrocketed during the last decade, and estimates suggest that 5% of mothers use at least one addictive drug during their pregnancy. To address this public health crisis, multiple groups—including the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics—recommend universal screening of substance use in pregnancy using standardized behavioral scoring tools. Unfortunately, such tools are often biased due to subjective scoring or self-reporting errors, and fail to identify babies who did not receive proper prenatal care. This project will develop a fast and accurate NAS screening tool that pairs a simple sample preparation protocol with a high-sensitivity panel of homogeneous enzyme immunoassays recognizing five common classes of drugs: fentanyl, morphine, amphetamine/methamphetamine, cocaine, and benzodiazepines. The potential benefits of such a system include reduced length of hospitalization for unaffected newborns, accelerated time to confirmatory results (under 2 hours), faster resolution of acute withdrawal symptoms, and improved referral to family/maternal support services.

There is an urgent need for non-opioid post-operative pain management solutions.  This research is developing a naturally absorbable polymer film that can release controlled amounts of the non-opioid analgesic bupivacaine – aiming to manage pain for several days following surgery. Project objectives are to optimize the timing of drug release, develop manufacturing standards, determine effective dosage for preserving motor function, and determine safety and efficacy in mouse models of neuropathic pain. Continued development of this film delivery system may lead to a new, non-opioid therapeutic strategy that could be combined with local anesthesia for up to 4 days after surgery to reduce or potentially eliminate opioids use.

Naltrexone is the only medication approved by the U.S. Food and Drug Administration to prevent relapse from opioid use disorder. This medication remains underused because it must be injected into muscle by a nurse and is relatively expensive. This project will develop and test a novel naltrexone skin patch that is easier to use, more comfortable, and inexpensive.

Research shows that individuals with chronic pain may experience brain changes that contribute to anxiety, depression, and cognitive impairment. This project will test a user-friendly, home-based device to treat chronic pain. The device stimulates the brain through olfactory training: repetitive daily stimulation with specific smells. The research will optimize a treatment approach and test the device in a clinical study.

Novel therapies that could alleviate the severe symptoms of opioid withdrawal and/or reduce risk of relapse could help address the devastating opioid crisis. Memantine, an FDA-approved NMDA receptor antagonist, has shown encouraging results as an adjunct to existing opioid use therapies. Its therapeutic efficacy likely derives from its preferential binding to NMDA receptors located outside the synapse, since broad spectrum NMDA receptor antagonists are associated with multiple clinical side effects. This project will use a preclinical model to evaluate a nanostructured version of memantine (AuM) that physically prevents its binding to synaptic NMDA receptors but allows activation of extrasynaptic receptors with potency exceeding that of free memantine.

Non-punishment, support-based preventive interventions in schools are needed to reduce misuse of opioids and other substances among youth. This project will test an intervention to improve school climate by introducing a learning approach that encourages behavior that is supportive and respectful in middle schools. ISLA reduces the use of exclusionary and discipline practices, such as suspensions and expulsions, that can be racially discriminating. The research aims to improve inclusive teaching practices, student engagement, student-teacher relationships, and school climate, while reducing student misuse of opioids and other substances.

Social determinants of health are individual and environmental factors that affect health, the ability to function, and quality of life. This project will study the impact of the family-focused Families Actively Improving Relationships (FAIR) prevention intervention currently offered in rural Oregon counties to parents experiencing substance use and mental health challenges. Through the FAIR program, participants receive substance use treatment services; mental health treatment services; parent management training; and support to access employment, housing, education or to mitigate exposure to violence and discrimination. This research will examine how the FAIR intervention affects substance use and societal determinants of health, toward informing payors and decision makers about the cost and value of FAIR prevention services in rural communities.