Funded Projects

This project will develop PIDA, which will allow researchers to measure the activity of pain-sensitive human neurons in response to pain stimuli and potential pain treatments. The tool will use automated digital microscopes in the absence or presence of a potential pain medication. Since this tool contains human neurons, it may be more effective at predicting the efficacy of potential pain drugs in human patients than the animal models that are currently used.

Hesperos uses microphysiological systems in combination with functional readouts to establish systems capable of analysis of chemicals and drug candidates for toxicity and efficacy during pre-clinical testing, with initial emphasis on predictive toxicity. The team constructed physiological systems that represent cardiac, muscle and liver function, and demonstrated a multi-organ functional cardiac/liver module for toxicity studies as well as metabolic activity evaluations. In addition, the team demonstrated multi-organ toxicity in a 4-organ system composed of neuronal, cardiac, liver and muscle components. While much is known about the cells and neural circuitry regulating pain modulation there is limited knowledge regarding the precise mechanism by which peripheral and spinal level antinociceptive drugs function, and no available human-based model reproducing this part of the pain pathway. The ascending pain modulatory pathways provide a well characterized neural architecture for investigating pain regulatory physiology. In this project, the research team propose a human-on-a-chip neuron tri-culture system composed of nociceptive neurons, GABAergic interneurons and glutamatergic dorsal projection neurons (DPN) integrated with a MEMS construct. Using this model, investigators will interrogate pain signaling physiology at three levels, 1) at the site of origin by targeting nociceptive neurons with pain modulating compounds including noxious stimuli and inflammatory mediators, 2) at the inhibitory GABAergic interneuron, and 3) at the ascending spinal level by targeting glutamatergic DPNs. These circuits will be integrated utilizing expertise in patterning neurons as well as integration with BioMEMs devices. This system provides scientists with a better understanding of ascending pain pathway physiology and enable clinicians to consider alternative indications for treating pain at peripheral and spinal levels. 

Fifty million Americans experience chronic pain, including about 25 million who report pain that substantially interferes with daily activities and reduces quality of life. Mental health problems, including depression, anxiety, and post-traumatic stress disorder, increase risk for severe chronic pain. This project will use genetic data, information about observable characteristics (phenotypic data), and neuroimaging data from three large databases to identify psychosocial factors that predict chronic pain, assess differences across diverse U.S. populations, and determine whether risk profiles predict post-surgical chronic pain.

Chronic pain remains a significant global heath challenge. Development of novel safe and effective treatments requires a deeper understanding of the molecular and cellular mechanisms that underlie the development of chronic pain. One protein that has been implicated in controlling the transition from acute to chronic pain is N-acylethanolamine acid amidase (NAAA). This project will evaluate how NAAA controls pain susceptibility after an acute insult and how this affects the emergence of chronic pain.

Musculoskeletal pain is common, costly, and affects millions of Americans. Clinical guidelines strongly recommend complementary and integrative treatments such as physical therapy, but nearly half of people receiving physical therapy for musculoskeletal pain seek additional care. Additional treatments such as medication and surgery are more aggressive and carry higher risk. This project will use data from a large physical therapy dataset and nationwide medical claims data to investigate why some people do not respond well to physical therapy for musculoskeletal pain, toward finding safe and effective options for these individuals.

Some chemotherapy treatments damage nerves outside the brain and spinal cord. This condition, chemotherapy-induced peripheral neuropathy, involves tingling, burning, weakness, or numbness in hands and/or feet and affects nearly 70% of cancer patients receiving chemotherapy. Common pain medications, including opioids, can relieve pain for short intervals but are not suitable for long-term therapy. This project will develop and test a new type of treatment (reduced size cyclic analogs) for this condition. The research will evaluate the ability of this therapy to reduce inflammation and pain, as well as to repair nerve damage.

Pain is common, complex, and debilitating in many cancer patients. Although adequate pain management can significantly improve health-related quality of life for these individuals, substantial disparities limit care access, especially among underserved populations. After the 2014 Drug Enforcement Agency policy that raised the risk potential of the opioid hydrocodone (from Schedule III to Schedule II), few studies examined the impact of this policy on pain management strategies and outcomes among cancer patients. This project will use national cancer registry data linked with Medicare claims to assess the change in opioid and non-opioid medication use among older lung cancer patients before and after this policy change. By focusing on older racial/ethnic minority groups dually eligible for both Medicare and Medicaid, the research will also examine disparities in the use of medications for pain management and service use consistent with inadequate pain management.

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. 

Chronic pain affects millions of Americans and remains poorly understood and challenging to manage. Researchers do not fully understand brain processes involved in chronic pain, which can vary considerably from person to person. This project will analyze brain function using magnetic resonance imaging (MRI) in individuals with and without chronic pain. The research will also directly determine the degree of pain-related brain imaging changes by using a large database of brain imaging data.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a first line pharmacologic pain therapy for chronic musculoskeletal pain, and rheumatoid arthritis (RA) and moderate to severe osteoarthritis (OA) specifically. However, insufficient pain relief by NSAID monotherapy has encouraged the use of combination therapy. Combinations of NSAIDs plus weak opioids are widely used although objective evidence for efficacy is limited and they have many adverse events.  A growing body of evidence suggests that ?2/?3 subtype-selective positive allosteric modulators (PAM) of the ?- aminobutyric acid A receptor (GABAAR) may effectively restore central pain regulatory mechanisms thus providing effective relief of chronic pain with reduced prevalence and severity of side-effects.  Based on these promising preliminary studies and considerable supporting literature data, the research team will test the hypothesis that combination dosing of TPA-023B with an NSAID will work synergistically to suppress the acute and chronic pain components of chronic musculoskeletal pain. 

Knee osteoarthritis is one of the leading causes of chronic pain and disability worldwide, affecting more than 30% of older adults. Rates of this condition have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and body mass index among the U.S. population. This project supports a scientist from a group underrepresented in biomedicine to expand ongoing clinical research comparing various non-medication-based treatments for knee osteoarthritis.

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.

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.