Funded Projects

NOFO Title: Career Development Awards in Implementation Science for Substance Use Prevention and Treatment (K01 - Clinical Trial Required) 
NOFO Number: PAS-22-206
Summary:

Many people with opioid use disorder (OUD) also have a serious mental illness and other chronic conditions, which can be difficult for individuals and primary care providers to manage. A chronic disease self-management program is an established health care model in which peers help to educate patients about their condition(s) and build problem-solving skills to manage their health. Such programs have been effective in other populations and settings, but they have not been adapted for primary care patients who have OUD and SMI. This project will adapt and test a chronic disease self-management program for this population to understand its feasibility, acceptability, impact, and how best to put such programs into place widely in primary care settings.

NOFO Title: Innovation Award for Mechanistic Studies to Optimize Mind and Body Interventions in NCCIH High Priority Research Topics (R33)
NOFO Number: RFA-AT-16-006
Summary:

Low back pain (LBP) is a common and costly condition. Spinal manipulative therapy (SMT) is a common mind-body intervention for individuals with LBP. Studies that have supported SMT have generally found relatively small treatment effects. The prior work of this research team has identified two mechanisms explaining the therapeutic effects of SMT: a reduction in spinal stiffness and improved activation of the lumbar multifidus muscle. Our research team has also developed accurate, non-invasive methods to measure these effects and their response to SMT. Our overall goal is to optimize SMT treatment protocols for patients with LBP. In this project, we will use innovative methodology to efficiently evaluate the effects of various individual treatment components toward an overall effect. Results of this project will provide optimized SMT protocols that will be ready for application in future randomized controlled trials examining the efficacy and effectiveness of SMT.

NOFO Title: CTSA Network - Trial Innovation Centers (TICs) (U24)
NOFO Number: RFA-TR-15-002

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:

Using neural tissues from pain patients, this project will investigate mechanisms of neuronal and/or immune dysfunction driving chronic pain. The researchers will use spatial transcriptomics on human dorsal root ganglion (DRG) and spinal cord tissues to examine the cellular expression profile for these targets using the 10X Genomics Visium technology. The use of tissues from control surgical patients and organ donors as well as surgical patients with neuropathic pain will enable validation of expression of these targets in human tissue as well as indication of their potential involvement in neuropathic pain. This collaborative effort will use DRGs removed from pain-phenotyped patients during neurological surgery, as well as lumbar DRGs and spinal cord from organ donors. This study will map the spatial transcriptomes at approximately single cell resolution in the human DRG and spinal cord.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Effective treatments are elusive for the majority of patients with neuropathic pain. Reactive oxygen and nitrogen species (ROS/RNS) are involved in neuropathic pain, because they drive mitochondrial dysfunction, cytokine production, and neuronal hyperexcitability; therefore, stimulation of endogenous antioxidants is predicted to simultaneously resolve multiple neuropathic pain mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that is a potential therapeutic target because it regulates the expression of a large number of endogenous antioxidant-related genes and can be activated with a single drug. This project will test the hypothesis that Nrf2 activation increases multiple endogenous antioxidants, therefore reversing neuropathic pain behaviors and counteracting neuropathic pain mechanisms that are driven by ROS/RNS and could provide an effective pain therapy, with minimal abuse/addictive potential.

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

This training and dissemination project will develop an office-based buprenorphine treatment module for primary care, including the algorithm for buprenorphine treatment and integration of OUD measures; assess the acceptability of the OUD module; evaluate the impact of the OUD module on screening and identification rates of problem opioid use and successful initiation and maintenance rates of buprenorphine in primary care; assess barriers to implementation of buprenorphine treatment and methods for overcoming these barriers in the network partner clinics; and develop a strategy to refine and more broadly implement opioid problem use and OUD treatment.

NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Chronic pain from tissue injury often stems from long-term changes in spinal cord circuits that change nerve sensation. Reversing these changes may provide better pain therapeutics. Previous work in animal models showed that activating G protein-coupled receptor 37 (GPR37) dampens nerve signal intensity after long-term stimulation and alleviates pain behavioral responses. This project aims to validate GPR37 in the spinal cord as a useful target for new treatments for neuropathic pain. The work will facilitate screening and identification of new molecules that activate GPR37, which can then be tested for efficacy and safety in further research in animal models of pain.

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

Functional selectivity is a term used to describe the ability of drugs to differentially regulate the activity of multiple signaling cascades coupled to the receptor. The underlying mechanism for functional selectivity is based upon the formation of ligand-specific receptor conformations that are dependent upon ligand structure. Functional selectivity has the potential to revitalize the drug discovery/development process. Ligands with high efficacy for specific signaling pathways (or specific patterns of signaling) that mediate beneficial effects, and with minimal activity at pathways that lead to adverse effects, are expected to have improved therapeutic efficacy. We propose to demonstrate that ligand efficacy for specific signaling pathways associated with antinociception can be finely tuned by structural modifications to a ligand. We propose to use U50,488 and Salvinorin-A (Sal-A) as scaffolds to develop functionally selective analogs that maintain high efficacy for signaling pathways that lead to antinociception and minimize activity toward anti-antinociceptive signaling pathways.

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.

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: 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.