Funded Projects

NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-016
Summary:

Currently, there are no adequate therapies for abdominal pain in patients with Irritable Bowel Syndrome (IBS), a gastrointestinal disorder affecting 14-20% of the US population. More than 40% of IBS patients regularly use opioid narcotics. An alternative treatment for IBS that has been shown to be an effective pain management strategy is electroacupuncture. However its drawbacks include infrequent administration, unclear mechanistic understanding, and lack of methodology optimization. This study will use a noninvasive method of transcutaneous electrical acustimulation (TEA) by replacing needles with surface electrodes and testing acupoints that target peripheral nerves. Based on prior mechanistic and clinical studies, two stimulation parameters and effective acupoints will be tested. In the UG3 phase, the TEA device and a cell phone app will be optimized for use in IBS abdominal pain, and an acute clinical study will determine the best stimulation locations and parameters. During the UH3 phase, an early feasibility clinical study will be performed in 160 IBS patients in treating abdominal pain. Participants will self-administer the therapy at home/work and will be randomized across four treatment groups to determine the therapeutic potential of the TEA system.

NOFO Title: Development and Validation of Pain-Related Models and Endpoints to Facilitate Non-Addictive Analgesic Discovery
NOFO Number: NOT-NS-22-095
Summary:

Effective development of non-addictive therapies for pain requires animal models that reflect the human condition. Unfortunately, currently used models have limitations and have not always done a good job of predicting what will work in human patients. This project will refine a new way of measuring pain-related behaviors in mice that takes advantage of more natural mouse behavior and is less influenced by experimenter biases and artifacts. The research will verify that the promising results hold up in several different types of pain and that different classes of clinically used pain medications are effective. They will also make sure the data can be reproduced by an outside laboratory. If successful, this will support the use of this new read-out for future pain therapy development.

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:

The proposed Fast Track SBIR effort will develop and validate the reliable, low-cost KnowPain instrument. KnowPain will objectively and quantitatively assess the functional impact of chronic pain using measures derived from six degrees-of-freedom motion, heart rate, skin surface temperature, and skin conductivity collected via a specially designed, ergonomic wrist-worn biometric sensing instrument. The new assessment instrument will apply advanced psychometric methods to both physiologic and kinematic data to provide precise scores for functional impairment due to chronic pain. The assessment results will be presented to the clinician in an easy-to-understand report and will include longitudinal results, confidence estimates, and normative data to enable comparisons both within and between patients. The system will include provision to interface with electronic medical records. Accurate functional assessment is a crucial component in the effective treatment of chronic pain. The proposed approach will supplement existing methods for assessing patient function by providing novel and highly complementary information for a more complete (and often unobserved) picture of the impact of chronic pain on patient function. KnowPain measures will provide important data on the practical consequences of pain and on treatment efficacy. 

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

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. 

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:

Although opioid-based analgesics have been proven effective in reducing the intensity of pain for many neuropathic pain conditions, their clinical utility is grossly limited due to the substantial risks involved in such therapy, including nausea, constipation, physical dependence, tolerance, and respiratory depression. Cumulative evidence suggests that human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain with limited side effects due to its restricted expression in nociceptors within the peripheral nervous system; however, direct activation of MRGPRX1 at peripheral terminals is expected to induce itch side effects, limiting the therapeutic utility of orthosteric MRGPRX1 agonists. This finding led to the exploration of positive allosteric modulators (PAMs) of MRGPRX1 to potentiate the effects of the endogenous agonists at the central terminals of sensory neurons without activating peripheral MRGPRX1. An intrathecal injection of a prototype MRGPRX1 PAM, ML382, effectively attenuated evoked, persistent, and spontaneous pain without causing itch side effects. The goal of this study is to develop a CNS-penetrant small-molecule MRGPRX1 PAM that can be given orally to treat neuropathic pain conditions.

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

Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. While our understanding of the development of chronic pain has improved, the available therapeutics provide limited relief. We will examine the peripheral immune and inflammatory response. Secondary inflammation in response to SCI is a series of temporally ordered events: an acute, transient upregulation of chemokines, followed by the recruitment of monocytes/macrophages and generation of an inflammatory environment at the lesion site in the spinal cord, but also surrounding primary nociceptors in the dorsal root ganglia (DRG). These events precede neuropathic pain development. Previous work indicates that after SCI, macrophage presence in the DRG correlates with neuropathic pain. We propose to study: 1) whether the phenotype of macrophages that infiltrate the DRG is different than those that persist chronically after SCI and 2) how manipulation of macrophage phenotype affects nociceptor activity and pain development.

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

Pain is a major problem for spinal cord injury (SCI) patients that tends to persist and even worsen with time. No treatments are currently available to consistently relieve pain in SCI patients. This study will investigate the feasibility of Epidural Electrical Stimulation (EES) using the Abbott Proclaim? SCS system with two electrodes to treat neuropathic pain in patients with thoracic spinal cord injury. In this double-blind, prospective, randomized clinical trial, patients with subacute, traumatic, complete thoracic SCIs with American Spinal Injury Association (ASIA) Impairment Scale A will be randomized to receive either ?EES on? (treatment intervention) or ?EES off? (control intervention) of the target regions for pain control (lead overlying the spinal cord anatomy corresponding with their pain distribution) and neurorestoration (lead overlying the conus medullaris) as an adjunct to physical therapy. This study will help determine whether EES can help patients with SCI neuropathic pain and have more widespread clinical applicability.

NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

TWIK-related spinal cord K+ (TRESK) channel is abundantly expressed in all primary afferent neurons (PANs) in trigeminal ganglion (TG) and dorsal root ganglion (DRG), mediating background K+ currents and controlling the excitability of PANs. TRESK mutations cause migraine headache but not body pain in humans, suggesting that TG neurons are more vulnerable to TRESK dysfunctions. TRESK knock out (KO) mice exhibit more robust behavioral responses than wild-type controls in mouse models of trigeminal pain, especially headache. We will investigate the mechanisms through which TRESK dysfunction differentially affects TG and DRG neurons. Based on our preliminary finding that changes of endogenous TRESK activity correlate with changes of the excitability of TG neurons during estrous cycles in female mice, we will examine whether estrogen increases migraine susceptibility in women through inhibition of TRESK activity in TG neurons. We will test the hypothesis that frequent migraine attacks reduce TG TRESK currents.

NOFO Title: HEAL Initiative: National K12 Clinical Pain Career Development Program (K12 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-045
Summary:

The Interagency Pain Research Coordinating Committee has reported that early-stage investigators are leaving the clinical pain research workforce for other fields. In addition, pain clinician researchers at the senior/mentor level are also exiting the field. This project will create a national training center for early-career clinicians and scientists interested in pursuing and sustaining independent careers in clinical pain research. Research will focus on rigorous scientific methods and procedures in pain research as well as the importance of stakeholder engagement.

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

Debilitating pain is the most common complication of sickle cell disease (SCD), but there is significant variability in pain expression in these patients. Currently, there is no plasma biomarker that can prognosticate which patients are likely to experience pain. The overall goal of this proposed research is to develop a biomarker that prognosticates the clinical expression of pain in SCD. Project aims are to (1) derive the inflammatory index for pain by identifying inflammatory and immune regulatory gene probe sets that will distinguish healthy controls, patients with SCD in baseline health, and patients with SCD in acute pain and (2) determine whether co-expressed genes from patients with SCD correlate with clinical pain data. Subsequent aims are to (1) determine the clinically meaningful changes of the index in patients with SCD and (2) investigate the preliminary clinical validity of the index as a prognostic biomarker for pain in patients with SCD.

NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

Neck pain is the fourth leading cause of disability and also a significant cause of cervicogenic headaches. Many of the currently available neck pain treatments are invasive with associated risks and complications, particularly because of the complex anatomy. Magnetic resonance guided focused ultrasound, a novel, completely noninvasive technique, can precisely target spinal facet joints to help ameliorate neck pain, potentially transforming the current practices. The goal of this study is to develop a cervical spine-specific device and demonstrate its safety and efficacy on targeting cervical sensory fibers and the third occipital nerve. The results of these studies will provide an understanding on how to best use this technology for chronic neck pain as well as a basis for translation into human use.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107; PA-21-071
Summary:

Current evidence indicates that chronic pain after a traumatic injury is influenced by the body’s response to stress. This project will conduct a comprehensive analysis of gene expression after traumatic stress exposure in a range of animal models in various body regions including the brain (amygdala, hippocampus, hypothalamus) and spinal cord, as well as nerves and immune cells throughout the body. These studies will be conducted in animals with no stress exposure as well as in animals treated with a molecule (FKBP51) known to block the stress response. This research will enhance understanding of how FKBP51 and post-injury stress affect pain processes.