Funded Projects

About 14% of U.S. adults report experiencing migraine symptoms within any given 3-month period, making it the second most disabling illness in the world. Nonspecific pain medications used in migraine (e.g., acetaminophen, nonsteroidal inflammatory drugs, opioids) are often not effective for severe migraine symptoms or cause significant adverse effects. A research team of migraine care specialists, device and drug developers, and clinical research specialists has created a technology for accurately delivering self-administered migraine medication to the upper nasal cavity. The technology enables development of a self-administered therapy to provide rapid pain relief without harsh and addictive side effects of existing migraine medications. This project will establish efficacy and evaluate commercial design feasibility for this treatment.

Clinician bias causes inequities in healthcare, and interventions are needed to mitigate and eradicate this bias. This project aims to develop and test the impact of two interventions on overcoming clinician implicit bias in the management of pain for children from ethnic minorities treated in the emergency department. The study will include pediatric patients from under-represented minority groups with pain from long-bone fractures or acute appendicitis who are cared for by racially and ethnically diverse caregivers. Researchers will use stakeholder-informed approaches to establish quality of care metrics and then use clinician audit and feedback as well as data from electronic health records to quantify evidence of bias.      

A more thorough understanding of neuropathic pain is critical for developing new target-specific medications. Researchers know that peripheral nerve injury changes various cell processes that affect two ion channels linked with chronic pain. Preliminary studies indicate that molecular changes known as phosphorylation to the collapsin response mediator protein 2 (CRMP2), one of five intracellular phosphoproteins, promotes abnormal excitability in the brain region that contributes to neuropathic pain. This project aims to develop small molecule inhibitors of CRMP2 phosphorylation as potential therapeutics for pain.

Voltage-gated sodium channels such as Nav1.7, Nav1.8, and Nav1.9 transmit pain signals in nerve fibers and are molecular targets for pain therapy. While Nav channels have been validated as pharmacological targets for the treatment of pain, available therapies are limited due to incomplete efficacy and significant side effects. Taking advantage of recent advances in structural biology and computational-based protein design, this project aims to develop antibodies to attach to Nav channels and freeze them in an inactive state. These antibodies can then be further developed as novel treatments for chronic pain.

Digital health interventions, such as virtual reality (VR) applications, have become available for the treatment and monitoring of numerous health conditions, including pain management. A current HEAL-funded study is evaluating the role of a therapeutic VR approach for chronic low back pain. However, racial and ethnic disparities exist in patient access and response to such VR applications, as well as in the incidence and reporting of pain. For example, non-Hispanic Blacks and Hispanics are more likely to report severe pain than non-Hispanic Whites, yet are less likely to have access to digital health information and interventions. To address these disparities, this project will develop a framework to advance diversity and inclusion in digital health trials and will seek to increase the proportion of non-Hispanic Black and Hispanic participants in the ongoing VR trial by tailoring recruitment materials and using novel artificial intelligence-driven cohort building tools.

There is a clear public health imperative to improve the care and outcomes of people who experience severe acute and chronic pain. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) is charged with conducting deep phenotyping and biomarker studies for specific pain conditions – and with conducting high-quality phase II clinical trials to test novel non-opioid pain treatments with academic and industry partners. This research will extend EPPIC-Net’s current portfolio to develop novel and efficient data-analytic methodologies for complex medical data, such as those that are expected to be generated by the clinical trials conducted by EPPIC-Net.

The University of California, San Francisco, as part of the Back Pain Consortium (BACPAC) Research Program, has established a Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (REACH). The main goal of REACH is to define different subtypes (phenotypes) of chronic low back pain as well as to identify underlying pain mechanisms that can lead to effective, personalized treatments for patients across all population subgroups. To achieve this goal, REACH is, or will be, participating in several clinical trials, and it is imperative that the patients participating in these trials reflect the diversity of the U.S. population. Therefore, this project seeks to adapt methods that have successfully improved minority participation in other settings as well as to develop and deploy digital strategies that can promote recruitment and engagement of patients from marginalized populations.

This award funds EPPIC-NET’s first phase 2 clinical trial, testing the novel oral drug CNTX-6970 in patients with moderate to severe knee osteoarthritis pain. It will include 150 participants at EPPIC-Net sites across the United States. Preclinical studies of CNTX-6970, which binds effectively and dose-proportionally to C-C chemokine type 2 (CCR2) receptors, have demonstrated potent analgesia in multiple pain models, with no emergent safety issues. CNTX-6970 has effects both at an affected joint, as well as on neural signaling. Participants will be randomized to receive CNTX-6970, placebo, or a third pain medication and will be followed for 24 weeks.

Social determinants of heath may affect breast cancer diagnosis and disease staging at time of mastectomy. It is unclear if socioeconomic factors such as annual income, marital status/single parent household, number of children, distance from the hospital, and other life stressors facing individuals from under-resourced populations affect development of postmastectomy pain syndrome or response to the drug ketamine. This research will analyze these factors toward mitigating post-mastectomy pain. This analysis will also serve as the basis for further research to define pathways that minimize health disparities plays in the development of chronic, post-surgical pain. The ultimate goal of this research is to normalize risk for chronic pain after breast surgery.

Identifying optimal chronic low back pain treatments on a patient-specific basis is an important and unresolved challenge. Tailoring interventions according to patient movement characteristics is one option. This research is characterizing patients based on spinal motion during functional tasks and daily activities and will use artificial intelligence to objectively characterize motions of the spine during both clinical assessments and day-to-day life. During clinical assessments, participants will be asked to perform functional tasks while wearing motion sensors. Data collected from the sensors will be used to identify tasks of interest, such as activities of daily living and aberrant/painful motions. An artificial intelligence approach will then interpret data collected continuously during assessment in patients’ homes over a 7-day testing period. Ultimately, this data could be used to help clinicians tailor treatments that are responsive to a patient’s real-world functional impairments.

To avoid the reliance on opioids for treatment of pain, researchers are investigating alternative approaches to disrupt the transmission of pain signals by specialized neurons in the body, such as dorsal root ganglion neurons in the spinal cord. Molecules called voltage-gated sodium channels that are located in the membranes of dorsal root ganglion neurons are essential for transmission of the pain signals. People carrying a specific variant of these channels, NaV1.7, are insensitive to pain; therefore, strategies to block this particular channel might help in the development of non-addictive pain treatment approaches. Navega Therapeutics is developing an innovative gene therapy that specifically targets NaV1.7. Using studies in human cell lines, they will identify the best designs to then test this gene therapy approach in human dorsal root ganglion neurons.

Cancer remains a leading cause of death among Hispanic/Latino populations in the United States. Compared with non-Hispanic Whites, Hispanic/Latino cancer patients are more likely to experience poor quality of life and inadequate cancer-related care, including less effective pain relief and poor patient‒provider communication. Additionally, Hispanic/Latino populations often have inadequate access to pain treatment, due to both social disparities and language barriers. However, most behavioral and psychosocial oncology research continues to focus on non-Hispanic Whites, and empirically validated and effective treatment interventions, particularly psychosocial interventions, are often not available in Spanish. This project will generate a Spanish-language version of the painTRAINER internet-based coping skills training program that is both linguistically and culturally sensitive and will evaluate its feasibility and acceptability in Hispanic/Latino patients with persistent cancer-related pain.

A main goal of the NIH HEAL Initiative and the Early Phase Pain Intervention Clinical Network (EPPIC-Net) is to improve pain management by discovering and validating biomarkers and non-opioid pain medications. This award will leverage the resources at the University of Washington’s EPPIC-Net’s Specialized Clinical Centers by implementing and evaluating strategies to improve the engagement, recruitment, and retention of individuals from underserved racial/ethnic minority populations to participate in EPPIC-Net clinical trials. The site’s network spans multiple states and specialties, allowing access to geographically and demographically diverse patient populations, including underrepresented and underserved populations.