Funded Projects

Thoracic (chest) surgeries often cause both short-term (acute) and long-term (chronic) pain and long-term opioid use. Unique genetic and clinical risk factors affect individual responses to surgical pain and pain medications. Current trial-and-error approaches to managing post-surgical pain and opioid prescribing are not ideal. This project will develop predictive software within a medical device that takes into account an individual’s genetic and clinical information to predict the likelihood of chronic pain following thoracic surgery. 

Novel treatments for opioid use disorder are critically needed as the addiction and overdose crises continue. Neuromodulation is a promising supplemental treatment to standard care. The overarching project seeks to evaluate low-intensity focused ultrasound that targets the nucleus accumbens, a primary component of the brain’s reward neurocircuitry. This supplement will expand the number of participants in part of the study and will increase the project’s overall impact consistent with the original objectives and aims of the parent grant.

Multiple social determinants affect the health of youth experiencing homelessness. These include a lack of stable safe housing, income, education, food security, restricted access to services, as well as discrimination, victimization, and social isolation. This project will test the use of prevention efforts to address the factors that may be embedded within systems that serve this population, such as drop-in centers. The research will gather generalizable information about helping these youth along with cost estimates to inform future implementation efforts.

The primary goal of the PRECISION Human Pain network and its participating centers is to generate comprehensive datasets of molecular signatures and cellular function phenotypes or signatures of various cell types that underlie transmission and processing of pain signals in humans. To maximize the impact of the data generated through this effort, it is vital to standardize and integrate all data generated by the various centers and make these data available in a meaningful way to the larger scientific community. As the Data Coordination and Integration Center, this project will support the network to curate, harmonize, and effectively integrate center-generated datasets as well as provide operational support for the network and conduct educational and outreach efforts.

The International Classification of Diseases 10th revision codes are insufficient to accurately identify individuals who use opioids and stimulants together. This project will search already collected electronic health record data using a computer program to identify people with polysubstance use and determine what health care they receive. The research will improve understanding of polysubstance use in a region of Los Angeles, California, with very high rates of overdoses involving fentanyl and stimulants. 

There is an urgent need for a new generation of non-addictive, pain-relieving medications that do not cause problematic side effects like breathing problems or constipation. The overarching project is testing a new potential medication that interacts in a new way with the opioid system in human research participants. This supplement will help cover costs associated with the Safety Review Committee meeting required by the U.S. Food and Drug Administration.

Sleep and circadian rhythms are understudied risk factors for opioid use disorder (OUD) and its treatment. Opioids affect sleep quality in a way that can inhibit recovery. The two most effective medications for OUD also cause sleep problems. This project will increase understanding about underlying circadian and behavioral mechanisms, such as changes in craving and/or the ability to regulate emotions, that link poor sleep with suboptimal opioid treatment response outcomes.

Human oral cancer is associated with significant chronic pain, and a comprehensive understanding of the biology and mechanisms underlying this chronic pain is critical for developing better pain management strategies. This project will determine molecular characteristics, including a specific signaling system (endosomal GPCR kinase), associated with chronic oral cancer pain, using tissue samples obtained from patients with this condition. The findings will then be used to inform studies in animal models of human oral cancer pain to enhance understanding how endosomal GPCR kinase contributes to human oral cancer pain.

Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain. 

Exposure to prescription opioids during pregnancy can alter growth of the fetus and cause persistent neurological problems during childhood. This project will identify biological underpinnings of oxycodone exposure on health of the placenta, brain development of the fetus, and behavioral problems observed in early infancy. This research will also assess whether melatonin supplementation can limit these harmful outcomes. Overall, the research aims to characterize the health effects of oxycodone used during pregnancy, as well as to point to new tools and molecular indicators (biomarkers) for diagnosing, treating, and preventing opioid harm to the fetus and mother.

This project addresses the significant challenge of providing evidence-based, non-pharmacologic pain management to veterans with chronic pain living in rural regions. This research will test whether an innovative, virtual complementary and integrative group-based treatment will improve rural veterans’ pain management, function, and well-being. The research will also devise, evaluate, and adapt strategies for implementing this intervention while working with the health care system, veteran patients, and communities. The scalable, 12-week intervention includes pain education, mindfulness, pain-specific exercises, and cognitive behavioral strategies.

Medications for opioid use disorder (OUD) are safe and effective. However, many people do not take them long enough to achieve sustained recovery, putting them at risk of overdose. Peer recovery support services—which are delivered by trained individuals with lived experience of addiction and recovery—may help people with OUD initiate and stay in medication treatment. This project will adapt peer recovery support services for use in outpatient substance use treatment settings and test their implementation and effectiveness in helping people with OUD achieve long-term recovery. If successful, the program could be implemented in a variety of outpatient treatment programs, including in underserved rural areas.