Funded Projects

Chronic low back pain affects millions of people in the United States, resulting in high medical costs and lost productivity. New opioid-free treatments are needed to help people with chronic low back pain, but not all people respond equally to a given approach. IMPACT aims to use machine learning to analyze data such as physical activity, sleep, emotions, and pain levels and identify markers that can help predict how effective a mindfulness-based treatment approach (Mindfulness-Based Stress Reduction) can be for people with chronic low back pain.

There are currently no reliable tools to measure pain objectively, and health care providers must rely on patient’s subjective reports and observations of patient behavior to determine the level of pain a person experiences. This hampers both effective pain management and the development of new pain medications. This project will assess an imaging technology called Radiocaine that in animal studies has been able to identify the origin of pain as well as its intensity. The goal is to use Radiocaine in clinical trials for pain treatments, thereby enhancing treatment effectiveness and facilitating development of new treatments.

Recently, concerns have been voiced that medications to treat opioid use disorder (OUD) may contribute to dental problems, including cavities and tooth loss. These concerns may contribute to barriers preventing use of these medications. A better understanding of the effects of these medications on oral complications is critical. This project will use national databases to link dental, medical, and pharmacy claims data for Medicaid- or commercially-insured new users of various medications for OUD to determine and compare oral health outcomes. The project will also examine the perspectives and experiences of people with OUD on oral health.

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.

Immune checkpoint proteins regulate the immune system to prevent it from indiscriminately attacking cells. Some cancers activate these immune checkpoints to avoid attack, and drugs that target certain immune checkpoints are approved for cancer treatment. The same pathway may also be involved in pain because immune checkpoint proteins, such as programmed death 1 (PD-1) and the molecule that binds to it (programmed death ligand 1 [PD-L1]), also are found in sensory neurons, microglia, and macrophages. This project will investigate PD-1/PD-L1 in different cell populations to determine their contribution to pain and to the effects of opioids such as morphine. This knowledge may help identify new drugs for pain management that modify immune checkpoint activity.

Activation of immune cells (microglia) in the central nervous system and neuroinflammation have emerged as key drivers of neuropathic pain. These processes can be triggered by release of ATP, the compound that provides energy to many biochemical reactions. The source and mechanism of ATP release are poorly understood but could be targets of novel treatment approaches for neuropathic pain. This project will use genetic, pharmacological, and electrophysiological approaches to determine whether a large pore channel called Swell 1 that spans the cell membrane is the source of ATP release and resulting neuropathic pain and thus could be a treatment target.

Cerebral palsy (CP), the leading cause of childhood disabilities in the United States, refers to a group of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination. The experience of pain is one of the most common, poorly understood, and inadequately treated conditions in CP, impairing health and quality of life for both patients and caregivers. To understand why pain and motor dysfunction occur together, a model that accurately replicates both is needed. This project will validate an established, rabbit model of CP motor dysfunction for use in studying and developing effective treatments for CP-associated pain.

Knee osteoarthritis (OA) is a frequent cause of disability and chronic pain. Treatment often relies on analgesics like opioids to manage OA pain, with all the associated risks; other approaches to treat OA are often invasive and inaccessible to patients. Therefore, novel analgesic strategies are needed to reduce the high burden of knee OA-induced pain. This project aims to study in detail and target the sensory neurons that drive OA pain to assist in the development of more effective pain therapeutics.

Buprenorphine is used for treatment of opioid use disorder (OUD), and patients often take it for many years by slowly dissolving it in the mouth. In 2022, the U.S. Food and Drug Administration warned about possible oral complications from buprenorphine use, including tooth decay, oral infections, and tooth loss. However, this warning was largely based on small studies with no comparison group and no assessment of other risk factors such as limited dental care. This project will follow two groups of individuals with OUD who take either sublingual buprenorphine or methadone, to compare their oral health and understand barriers and facilitators of dental care. The results will be used to plan an intervention for preventing and treating oral diseases in this patient group.

Sublingual buprenorphine is a standard treatment for opioid use disorder and is considered safe and effective. However, in 2022 the U.S. Food and Drug Administration advised that buprenorphine is linked to oral disease. However, the underlying studies did not measure when oral disease started, how it progressed, or if other risk factors were present. How sublingual buprenorphine may impact oral health also remains unclear. This project will follow adults in two U.S. states who take sublingual buprenorphine or other medications for opioid use disorder to understand if and how these medications increase the extent, onset, and progression of oral disease, accounting for other risk factors.