Funded Projects

NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

High-voltage-gated calcium channels convert electrical signals into physiological responses. After a nerve injury, levels of these channels go down in some neurons in the dorsal root ganglia that communicates pain signals to and from the brain. This decline results in reduced flow of calcium that may underlie pain. This project will develop novel approaches to block these calcium channels p to further study their roles in controlling pain.

NOFO Title: HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
NOFO Number: NS22-016
Summary:

Spinal cord stimulators (SCS) and related devices are commonly used for hard-to-treat pain conditions, but how they work remains unclear. This knowledge is important for improving device design and stimulation patterns, as well as for determining which patients will benefit. Through a series of clinical studies in patients with SCS devices, this project will explore the hypothesis that SCS devices reduce pain by changing the excitability of peripheral sensory nerve fibers in the spinal cord. The results should guide development of biomarkers to advance research further.

NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Chronic pain severely reduces the quality of life and ability to work for millions of Americans. Because misuse of opioids for chronic pain treatment contributes to opioid addiction and opioid overdose, there is an urgent need to study novel non-opioid mechanisms, targets, and treatment strategies for chronic pain. Many ion channels control the flow of electrical signals in peripheral sensory neurons and are thus key targets for understanding and treating chronic pain. This project will conduct detailed studies to identify major ion channel-related molecular activities, targets, and treatment strategies for chronic pain. In particular, this research will explore the role of a specific ion channel (lysosomal mechanosensitive ion channel, orTmem63A) in neuropathic pain resulting from nerve injury.

NOFO Title: HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
NOFO Number: NS22-016
Summary:

Despite the need for non-opioid treatments for chronic pain, few alternative treatment approaches exist. Transcutaneous auricular neurostimulation (tAN) is a safe and effective treatment for pain during opioid withdrawal; however, researchers do not understand how tAN reduces pain, which limits its clinical use. A better understanding of how tAN affects neurophysiological processes to provide pain relief would likely expand tAN development and use. This interdisciplinary project will conduct research in both healthy adults and those with chronic pain to explain the neurochemical and neurophysiological mechanisms for tAN-based pain relief, and also help optimize treatments and their use.

NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Opioids affect the body by attaching to certain types of receptors that attach to G-proteins (particularly, a subtype called G-alpha). Opioids vary in their ability to provide pain relief as well as in their ability to require more drug to provide a response, known as tolerance. This project will explore the potential of various G-alpha subunits to increase or decrease opioid receptor signaling. The research findings will lay the groundwork for tailoring G-alpha related opioid effects to provide more pain relief while being less addictive.

NOFO Title: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp Clinical Trial Not Allowed)
NOFO Number: PA21-071
Summary:

There are significant and persistent gaps in knowledge about effective pain management for acute and chronic sickle cell pain. This is an area of relevant interest for the NIH HEAL Initiative's Early Phase Pain Investigation Clinical Network (EPPIC-Net). In order to provide guidance for hospital-based administration of the medication ketamine, this project will conduct a cross-sectional survey study of healthcare professionals within EPPIC-Net who provide care for people with sickle cell disease. This information can be used to design a clinical protocol for a multisite, randomized clinical trial of sub-anesthetic (low) doses of ketamine for challenging vaso-occlusive episodes (“pain crises”) in people with sickle cell disease.

NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Routine treatment of pain with prescription opioid medications may evolve into opioid use disorder, addiction, and potentially overdose. New, non-opioid molecular targets for pain are needed as a key element of responding to the opioid and overdose crisis. Ion channels are molecular gateways that convert electrical signals into physiological responses, and many have been implicated in transmitting pain signals. The ion channel Kir6.1/KCNJ8 has been linked to the control of postoperative and cancer pain. Studies in animal models show that low levels of this ion channel are evident after an injury. This research will identify compounds that can open the Kir6.1/KCNJ8 channel as potential treatment strategy for pain.

NOFO Title: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp Clinical Trial Not Allowed)
NOFO Number: PA21-071
Summary:

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.

NOFO Title: HEAL Initiative: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management
NOFO Number: RFA-AT-22-003
Summary:

Pain in muscles and surrounding connective tissue (myofascial pain) is a significant health concern affecting hundreds of millions of Americans. There is no objective way to identify and measure myofascial pain. This project will address this unmet challenge by developing a robust approach to identify imaging biomarker(s) that can distinguish different states of myofascial pain. The research will then examine the ability of identified biomarker(s) to predict patient responses to a myofascial pain treatment in a randomized controlled clinical trial.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

This research project will include focus group interviews with clinicians, patients, medical interpreters, and healthcare administrators to identify barriers and facilitators to administering the GetActive+ intervention in a group visit at a clinic for older adults with chronic pain, to inform development of a therapy manual. The project will then test the GetActive+ intervention for changes in physical function immediately post-intervention and after 6 months, as well as for changes in pain, sleep, depression, and anxiety at both time points. This research will also assess feasibility, acceptability, fidelity, and adoption of the intervention with patients, providers, and healthcare staff. 

NOFO Title: HEAL Initiative: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management
NOFO Number: RFA-AT-22-003
Summary:

Pain in the muscles and surrounding connective tissues (myofascial pain) can affect many regions of the body and is a key component of chronic low back pain. Patients with chronic low back pain have a range of musculoskeletal problems perpetuating their pain. There is a significant clinical need to identify the components of myofascial pain in people with chronic low back pain. Advances in ultrasound technology have allowed researchers to identify several differences in muscle and connective tissues related to myofascial pain. This project will develop and validate an ultrasound-based biomarker signature for myofascial pain in the low back. This research will also refine the biomarker signature using advanced machine learning approaches, toward future testing in in a randomized controlled clinical trial.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

Cancer pain treatment disparities are associated with a decreased ability to tolerate treatment, as well as increased rates of disability, unemployment, institutionalization, and early death. The Achieving Equity through SocioCulturally-informed, Digitally-Enabled Cancer Pain managemeNT (ASCENT) clinical trial will test whether a novel digitally enabled, collaborative approach to team-based pain management can improve clinical outcomes and reduce long-standing and devastating disparities among rural dwelling and Hispanic/Latinx cancer survivors. A major focus of the randomized, effectiveness clinical trial is to test the hypothesis that the ASCENT intervention will reduce pain and unplanned healthcare use, while improving function, mood, sleep, and quality of life.