Funded Projects

NOFO Title: HEAL Initiative: Development and Validation of Non-Rodent Mammalian Models of Pain (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-070
Summary:

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.

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: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain (Admin Supp – Clinical Trial Not Allowed)
NOFO Number: NOT-NS-21-048
Summary:

Improving pain treatment for is a major goal of the NIH HEAL Initiative. This award supports an early career physician toward achieving a future in clinical pain research and in conducting phase II clinical trials focused on pain. Research activities will provide this individual with the skills needed to serve as a primary investigator for future clinical trials in chronic pain and will help to answer a key question that could improve the design of analgesic clinical trials for neurogenic intermittent claudication, a distinct form of chronic low back pain for which no available treatment exists.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

Osteoarthritis is a degenerative joint disease marked by progressively worsening chronic joint pain that affects function and quality of life. Non-opioid, alternative medications are needed for people with this condition. Joint inflammation, damage, and pain involve signaling through the interleukin-6/glycoprotein 130 pathway. This project will test blocking this pathway in rodents with a new molecule with improved drug-like properties, toward developing an oral medication for osteoarthritis. 

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Buprenorphine-naloxone is known to work for the treatment of Opioid Use Disorder (OUD). However, despite its success in treating OUD, retention for these kinds of medication-assisted treatments (MATs) for OUD is notoriously low, having a dropout rate of approximately 50 percent within the first 6 months. One factor known to negatively impact a person?s adherence to treatment is stigma. This includes, not only stigma associated with having OUD, but also that of multiple stigmatized identities, including stigma associated with race. The goal of this supplement award is to decrease OUD- and race-related stigma in low income African American communities using a Behavioral Economics Stigma Reduction intervention that functions at the intrapersonal, interpersonal, and community levels. The investigators will work at the individual level to address stigma in untreated individuals who present with OUD at local community or faith organizations through stigma reduction counseling and tangible rewards for treatment uptake. To assess the interpersonal stigma, referred family members or support persons of these individuals will also be enrolled to receive stigma reduction and supportive skills counseling. Finally, a stigma reduction campaign will be developed and administered to the community via social media and billboards. Community members? substance use stigma will be compared before and after the campaign.

NOFO Title: HEAL Initiative: Development and validation of virtual assessments to study children and caregivers in their natural environment (R01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-23-050
Summary:

High-quality parent-infant interactions set the stage for secure parent-child attachment, self-reliance, and children’s ability to flexibly solve problems and “bounce back” from difficulties. This constellation of behaviors reduces the risk of developing substance use disorders later in life. This project will develop algorithms that use data from wearable sensors, trained separately for English- and Spanish-speaking families, to assess the quality of early mother-infant interactions objectively, automatically, and remotely in natural home environments, with the goal of developing tools to facilitate identification and prevention of early risks for substance use disorders.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Migraine is the most common neurological disorder. Currently available treatments fail to effectively manage migraine in most patients. Development of new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). The central hypothesis is that PAR2 expression in nociceptors that project to the meninges plays a key role in the pathogenesis of migraine pain. The aims are to: 1) use the established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like properties; 2) use pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in migraine; and 3) use mouse genetics to study the cell type–specific role of PAR2 in migraine pain.

NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

This study aims to determine whether a subset of understudied genes that are expressed in human and mouse dorsal root ganglia (DRG) tissues (critical for relaying the sensation of pain from the body to the central nervous system), are also expressed in human induced pluripotent stem cell DRG mimetics. The study will also determine if these genes are involved in neuronal excitability changes under inflammatory conditions and compare these responses to those of primary DRG neurons. Third and finally, the study will optimize genetic depletion of target genes enabling future fundamental and preclinical research studies.

NOFO Title: HEAL Initiative: Research Networks for the Study of Recovery Support Services for Persons Treated with Medications for Opioid Use Disorder (R24 Clinical Trial Optional)
NOFO Number: RFA-DA-22-043
Summary:

About 23 million Americans identify as being in recovery from opioid and other substance use disorders. While recovery support services are an established best practice to support people in recovery, there is little scientific evidence to support the efficacy and implementation of peer recovery support services, training approaches, and delivery models. Recovery support services are particularly lacking in the U.S. Southwest and for individuals who choose to take medications for opioid use disorder as part of their recovery pathway. This project will establish the Peer Recovery Innovation Network to address research gaps. This research will incorporate input from people with lived experience in all stages of the recovery process – toward helping to set the research agenda and conducting the research, as well as enhancing infrastructure for peer recovery support services research.

NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Debilitating neuropathic pain occurs in 40 percent to 70 percent of people who suffer from spinal cord injury (SCI). There are no distinguishing characteristics to identify who will develop neuropathic pain. The objective of this research is to develop a biomarker signature prognostic of SCI-induced neuropathic pain (NP). The aims of the project are to (1) identify autoantibodies in plasma samples from acute SCI patients to CNS autoantigens and determine the relationship between autoantibodies levels to the development of NP, (2) identify the autoantibody combination with maximal prognostic accuracy for the development of NP at six months after SCI, and (3) develop and optimize an assay to simultaneously measure several autoantibodies and independently validate the prognostic efficacy for NP using plasma samples collected prospectively. Establishing a panel will refine the prognostic value of these autoantibodies as biomarkers to detect who are vulnerable to NP and may be used to for development of nonaddictive pain therapeutics.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Multi-protein complexes have emerged as a mechanism for spatiotemporal specificity and efficiency in the function and regulation of myriad cellular signals. In particular, many ion channels are clustered either with the receptors that modulate them, or with other ion channels whose activities are linked. Often the clustering is mediated by scaffolding proteins, such as the AKAP79/150 protein that is a focus of this research. This research will focus on three different channels critical to nervous function. One is the"M-type" (KCNQ, Kv7) K+ channel that plays fundamental roles in the regulation of excitability in nerve and muscle. It is thought to associate with Gq/11- coupled receptors, protein kinases, calcineurin (CaN), calmodulin (CaM) and phosphoinositides via AKAP79/150. Another channel of focus is TRPV1, a nociceptive channel in sensory neurons that is also thought to be regulated by signaling proteins recruited by AKAP79/150. The third are L-type Ca2+ (CaV1.2) channels that are critical to synaptic plasticity, gene regulation and neuronal firing. This research will probe complexes containing AKAP79/150 and these three channels using"super-resolution" STORM imaging of primary sensory neurons and heterologously-expressed tissue-culture cells, in which individual complexes can be visualized at 10-20 nm resolution with visible light, breaking the diffraction barrier of physics. The researchers hypothesize that AKAP79/150 brings several of these channels together to enable functional coupling, which the researchers will examine by patch-clamp electrophysiology of the neurons. Förster resonance energy transfer (FRET) will also be performed under total internal reflection fluorescence (TIRF) or confocal microscopy, further testing for complexes containing KCNQ, TRPV1 and CaV1.2 channels. Since all three of these channels bind to AKAP79/150, the researchers hypothesize that they co-assemble into complexes in neurons, together with certain G protein-coupled receptors. Furthermore, the researchers hypothesize these complexes to not be static, but rather to be dynamically regulated by other cellular signals, which the researchers will examine using rapid activation of kinases or phosphatases. Several types of mouse colonies of genetically altered AKAP150 knock-out or knock-in mice will be utilized.

NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOFO Number: PA-18-484
Summary:

Opioids remain the gold standard for treating moderate to severe pain, but their use is limited by numerous adverse effects, including tolerance, dependence, abuse, and overdose. Adverse effects could be avoided by combining an opioid with another drug, such that smaller doses of the opioid (in combination with another drug) produce the desired therapeutic effect. Direct-acting serotonin type 2 (5-HT2) receptor agonists interact in a synergistic manner with the opioid morphine to produce antinociceptive effects, suggesting a 5-HT2 receptor agonist could be combined with small amounts of an opioid to treat pain, thereby lowering the risk associated with larger doses. Unfortunately, very little is known about interactions between 5-HT2 receptor agonists and other opioids. The proposed studies will evaluate the therapeutic potential of mixtures of opioids and 5-HT2 receptor agonists using highly translatable and well-established procedures to characterize the antinociceptive, respiratory-depressant (overdose), positive-reinforcing (leading to misuse), and discriminative-stimulus (subjective) effects of drug mixtures as well as the impact of chronic treatment on the development of tolerance to and physical dependence on opioids. If successful, these studies will provide proof-of-concept for this innovative approach to pain treatment and evaluate the utility of targeting 5-HT receptors for analgesic drug development.

NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Scientists do not know the details of how the nervous system interacts with the temporomandibular joint (TMJ) that connects the lower jaw with the skull. This project aims to comprehensively explain the functions, types, neuroanatomical distributions, and adaptability (plasticity) of specific nerve cells in the brain (trigeminal neurons) that connect with the TMJ. The research will analyze nerve-TMJ connections associated with chewing muscles and other structures that form the TMJ such as cartilage and ligaments. The project will analyze samples from both sexes of aged mice, primates, and humans with and without painful TMJ disorders. This research aims to uncover potential treatment and prevention targets for managing TMJ pain.