Funded Projects

NOFO Title: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-010
Summary:

Pain signals originate predominantly in a subset of peripheral sensory neurons that harbor a distinct subset of voltage-gated sodium (NaV) channels; however, current NaV channel blockers, such as local anesthetics, are non-selective and also block NaV channels vital for function of the heart, muscle, and central nervous system. Genetic studies have identified human NaV1.7, NaV1.8, and NaV1.9 channel subtypes as key players in pain signaling and as major contributors to action potential generation in peripheral neurons. ProTx-II is a highly potent and moderately selective peptide toxin that inhibits human NaV1.7 activation. This study will optimize ProTx-II selectivity, potency, and stability by exploiting the new structures of ProTx-II—human NaV1.7 channel complexes, advances in rational peptide optimization, and rigorous potency and efficacy screens to generate high-affinity, selective inhibitors of human NaV1.7, NaV1.8, and NaV1.9 channels that can define a new class of biologics to treat pain.

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:

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of pain and disability. Current challenges of managing OA are that there is no OA disease-modifying drug available, there are few effective treatment strategies, and there is an over-reliance on the use of opioids to manage OA-related joint pain. This project aims to validate vascular endothelial growth factor receptors 1 and 2 (VEGFR 1 receptor = Flt1) and (VEGFR 2 receptor = Flk1) as novel therapeutic targets for OA. This is based on a hypothesis that blocking these two specific receptors of VEGF will inhibit cartilage tissue degeneration and alleviate pain symptoms. This study will test the role of VEGFR-1 and -2 in multiple OA animal models using multiple available VEGF inhibitor molecules. The findings from these studies will develop a rationale for future clinical trials to target VEGFR-1 and -2 for OA patients and develop a novel non-addictive treatment for both joint pain and OA pathology.

NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018
Summary:

The research team will develop stimulation control algorithms to treat chronic pain using a novel device that allows longitudinal intracranial signal recording in an ambulatory setting. Subjects with refractory chronic pain syndromes will undergo bilateral surgical implant of temporary electrodes in the thalamus, anterior cingulate, prefrontal cortex, insula, and amygdala to identify candidate biomarkers of pain and optimal stimulation parameters. Six patients will proceed to chronic implantation of “optimal” brain regions for long-term recording and stimulation. The team will first validate biomarkers of low- and high-pain states to define neural signals for pain prediction in individuals. They will then use these pain biomarkers to develop personalized closed-loop algorithms for deep-brain stimulation (DBS) and test the feasibility of closed-loop DBS for chronic pain in weekly blocks. Researchers will assess the efficacy of closed-loop DBS algorithms against traditional open-loop DBS or sham in a double-blinded cross-over trial and measure mechanisms of DBS tolerance.

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

There is a need to improve access to treatments and address the stigma, bias, and mistrust that harm and isolate people with chronic pain, especially those from ethnic and racial minority populations. The Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE) Chronic Pain (CP) intervention blends cognitive-behavioral therapy, physical therapy, mindfulness, and pain education, and is delivered by a trilingual mobile app and supported by a telehealth pain coach who coordinates with doctors. The coach will collect and summarize patient reports on pain, depression, anxiety, substance use, and social factors, and share them with healthcare providers. In this project, researchers will create the digital tool and coaching protocol, develop educational and implementation strategies for healthcare providers, and conduct a pilot test. They will then perform a randomized clinical trial to compare INSPIRE to current treatment, analyze its effects, and evaluate outcomes.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Chronic focal neuropathic pain, which includes pain etiologies such as radiculopathy and radiculitis, focal peripheral neuropathies, and low back pain, affects as many as 25 million patients annually in the United States. Chronic focal neuropathic pain is maintained by genome-wide transcription regulation in the dorsal root ganglia (DRG) / spinal cord network. The transcription factors driving this regulation constitute a promising class of targets with the potential to alter the course of pain with a single treatment. DNA decoys are oligonucleotides that specifically inhibit the activity of certain transcription factors. AYX2 binds and inhibits Krüppel-like transcription factors (KLF) in the DRG-spinal cord. The goal of this Phase 1 proposal is to advance AYX2 toward an IND submission, allowing for human clinical trials. We propose in Aim 1 to characterize AYX2 pharmacokinetics in the cerebrospinal fluid and plasma and its distribution in the DRG, spinal cord and brain following an IT injection. With this information, AYX2 will be tested in a panel of complementary toxicology studies in Aim 2 to allow for final IND-enabling studies, supported by Phase 2 of the grant. This research will accelerate development of AYX2 as a novel drug candidate for the non-opioid treatment of pain.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575
Summary:

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves, but no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, the team will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain.  

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:

Neuropathic pain conditions are exceedingly difficult to treat, and novel non-opioid analgesics are desperately needed. Receptomic and unbiased transcriptomic approaches recently identified the orphan G-protein coupled receptor (oGPCR), GPR160, as a major oGPCR whose transcript is significantly increased in the dorsal horn of the spinal cord (DH-SC) ipsilateral to nerve injury, in a model of traumatic nerve-injury induced neuropathic pain caused by constriction of the sciatic nerve in rats (CCI). De-orphanization of GPR160 led to the identification of cocaine- and amphetamine-regulated transcript peptide (CARTp) as a ligand which activates pathways crucial to persistent pain sensitization. This project will test the hypothesis that CARTp/GPR160 signaling in the spinal cord is essential for the development and maintenance of neuropathic pain states. It will also validate GPR160 as a non-opioid receptor target for therapeutic intervention in neuropathic pain, and characterize GPR160 coupling and downstream molecular signaling pathways underlying chronic neuropathic pain.

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

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.

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:

The Acute to Chronic Pain Signatures (A2CPS) Program aims to identify combinations of biomarkers that predict susceptibility or resilience to the development of chronic pain. This career enhancement award will help a promising postdoctoral trainee gain access to tools and develop skills needed to pursue a career in clinical pain research. The research involves conducting collaborative multi-site cohort studies and analyzing A2CPS data to determine if a combination of metabolic and psychosocial biomarkers can be used to explain pre-surgery differences in pain, function, and disability in patients with severe knee osteoarthritis.

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-036
Summary:

The Helping to End Addiction Long-term? (HEAL) Initiative’s Early Phase Pain Investigation Clinical Network (EPPIC-Net) is a unique opportunity to impact the management of pain, through expeditious discovery and validation of biomarkers and analgesic therapies, and in-depth phenotyping. The University of Washington’s (UW) Division of Pain Medicine (UW Pain; “hub”) includes four core clinical sites. Committed spokes include specialty care clinics, primary care clinics, external academic medical centers, and health systems. To achieve the goals of the HEAL Initiative’s EPPIC-Net, the study group will (1) establish UW EPPIC-Net hub and spokes infrastructure, provide scientific leadership and administrative oversight, and apply expertise in design and conduct of high-quality multidisciplinary Phase 2 clinical trials and biomarker validation studies; (2) develop policies and procedures for rapid design, initiation, recruitment, conduct, and closure of high-quality multidisciplinary Phase 2 clinical trials and biomarker validation studies for specific pain conditions at UW Pain EPPIC-Net hub and spokes; and (3) establish mechanisms for communication, education and training, and performance assessment of the UW-EPPIC-Net hub and spokes, to assure efficient and timely utilization of resources to most effectively recruit research participants into EPPIC-Net.

NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (U44 Clinical Trial Optional)
NOFO Number: RFA-NS-19-017
Summary:

The research team will develop an implantable neural stimulation system to provide natural and intuitive sensation for prosthesis users. The nerve cuff technology meets the requirements for a sensory feedback system capable of providing consistent and controlled electrical stimulation. Coupled with a multichannel implantable stimulator, this electrode array will offer substantial improvement over existing options to treat phantom limb pain (PLP). In Phase I, researchers will finalize array architectures for evaluation in cadaver studies, complete integration of electrodes with our stimulator, conduct benchtop verification of electrical and mechanical performance, send implants for third-party evaluation of system biocompatibility, and complete a Good Laboratory Practice animal study to validate safety and efficacy. In Phase II, researchers will conduct a 5-subject clinical study to test the implantable stimulation system. Each unilateral prosthesis user will be implanted for one year as researchers evaluate the safety and efficacy of this implantable device to treat PLP.

NOFO Title: HEAL Initiative: Discovery of Biomarkers and Biomarker Signatures to Facilitate Clinical Trials for Pain Therapeutics (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-22-050
Summary:

Neuropathic pain is a chronic and difficult to treat condition that affects people in different ways. This project aims to personalize treatments based on individual pain profiles. The research will develop an inexpensive test using a technique called quantitative sensory testing to predict how a patient will respond to two common pain medications. The research will also look for other factors in blood that enhance the accuracy of these predictions.