Funded Projects

There are currently few effective therapies available for chronic nerve injury-induced pain, associated anxiety, and depression. This project aims to extend previous research aiming to uncover the mechanism of action of artificially modified immune molecules (humanized cholecystokinin-2 receptor [CCKBR] single-chain variable fragments [scFv]) on human neurons and how it reverses chronic pain and anxiety-like behaviors in mouse models. This potential treatment approach offers important advantages over existing therapies, including extreme specificity, higher affinity, brain/nerve penetrance, safety, and reduced self-immunogenicity.

The Interagency Pain Research Coordinating Committee has reported that early-stage investigators are leaving the clinical pain research workforce for other fields. In addition, pain clinician researchers at the senior/mentor level are also exiting the field. This project will create a national training center for early-career clinicians and scientists interested in pursuing and sustaining independent careers in clinical pain research. Research will focus on rigorous scientific methods and procedures in pain research as well as the importance of stakeholder engagement.

Rheumatoid arthritis is an autoimmune disease characterized by episodes of joint inflammation and pain. There are currently no safe and effective treatments that achieve long-term remission of the condition or the associated pain. Many patients use opioid medications to manage the pain and are at increased risk of developing opioid use disorder; therefore, additional treatment options are needed. In rheumatoid arthritis, pain-triggering sensory neurons interact with immune cells in the joints. This project aims to dissect the neuroimmune crosstalk underlying pain and inflammation in arthritic joints and uncover novel therapeutic avenues for this painful condition.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder, and overdose, gaps remain between those needing and those receiving prevention and treatment. There is a need to better understand how to make these programs and services most effective at a local level, a problem being addressed by the HEALing Communities Study. This project supports a scientist from a group underrepresented in biomedicine to continue ongoing work to test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings.

Current evidence indicates that chronic pain after a traumatic injury is influenced by the body’s response to stress. This project will conduct a comprehensive analysis of gene expression after traumatic stress exposure in a range of animal models in various body regions including the brain (amygdala, hippocampus, hypothalamus) and spinal cord, as well as nerves and immune cells throughout the body. These studies will be conducted in animals with no stress exposure as well as in animals treated with a molecule (FKBP51) known to block the stress response. This research will enhance understanding of how FKBP51 and post-injury stress affect pain processes.

Many molecular gates known as ion channels control the flow of electrical signals to sensory neurons and are thus key mechanisms and targets for understanding and interrupting pain signals. Recent breakthroughs in structural and computational biology shave illuminated specific molecular shapes of ion channels, which permits the improved design and refinement of small, stable protein-like molecules (peptide antigens). These peptides can stimulate an immune response that can then be targeted with a bioengineered antibody to match the peptide antigen. This project will test bioengineered antibodies in a rat model of chemotherapy-induced peripheral neuropathy within a region of the rat spinal cord that transmits signals to and from the brain.

Many individuals with opioid use disorder pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings is critical to addressing the opioid crisis. The Justice Community Opioid Innovation Network (JCOIN) is studying approaches to increase high-quality care for people with opioid misuse and opioid use disorder in justice populations. This research supports a scientist from a group underrepresented in biomedicine to expand capacity of the Mason Coordination and Translation Center that is managing logistics, stakeholder engagement, and dissemination of findings and products from the JCOIN network.

The Acute to Chronic Pain Signatures Program is developing a comprehensive data set that can be used to help predict which patients will recover from acute pain associated with surgery or injury and which ones will develop long-lasting chronic pain. This project will support an early career faculty member from a group underrepresented in biomedicine. The research will enhance skills development toward conducting and coordinating clinical pain research, generating omics datasets, advancing understanding of statistical methods, and other activities required for career development. 

An important step for identifying new, non-addictive chronic pain treatments is the search for new, non-opioid molecular targets that reflect the human condition. Recent findings show an increase in levels of two proteins (calcium channel alpha-2delta-1 subunit and thrombospondin) in sensory and spinal cord neurons after nerve injury. This increase is associated with the development of neuropathic pain. This project will determine if chronic injury to key nerve fibers involved in pain cause changes in rat behavior that indicate altered mood. These nerve fibers include the trigeminal nerve that communicates pain, touch, and temperature sensations from the face to the brain and the L5/6 spinal nerves often associated with back and leg pain. This research will also test whether small protein-like molecules (peptides) that block calcium channel alpha-2delta-1 subunit and thrombospondin also block the mood-related behaviors.

The Interagency Pain Research Coordinating Committee has identified a need for organized opportunities for early-stage pain researchers to meet and learn from more experienced pain researchers and mentors – who are exiting the field at a faster rate than they are being replaced. This project will create a coordinating center for early-stage pain researchers, with an online networking platform to encourage interactions and collaboration among these scientists. The research will also develop a training curriculum and make it accessible to NIH funded, early-stage pain scientists.

The Early Phase Pain Investigation Clinical Network (EPPIC-Net) conducts comprehensive analyses of observable traits (deep phenotyping) and aims to identify molecular and physiological signatures to help characterize specific pain conditions. To achieve these goals, researchers collect complex data using technologies such as magnetic resonance imaging of the brain, actigraphy, and electroencephalography. There is a need to train researchers to be able to extract key information from high-powered computing resources now widely available.  This research will complement the goals of EPPIC-Net by enhancing development of novel statistical methods to analyze complex data generated by EPPIC-Net pain studies.

Acute and chronic pain vary widely across patients, due in large part to genetic differences between individuals. The same variation occurs in preclinical animal models with diverse genetic backgrounds. The development of automated mouse “pain scales” using high-speed videography, machine learning, and custom software allows pain to be assessed in a quantitative manner in nonverbal animals. This technology will be used to identify genetically different mice with high or low pain sensitivity, which will facilitate the development of new therapeutic strategies to treat pain and reduce reliance on opioids.