Funded Projects

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 tissue (myofascial pain) is a significant health concern affecting hundreds of millions of Americans. Understanding and managing myofascial pain has been limited due to a lack of tools to help clinicians diagnose and treat this disorder. While past efforts to understand myofascial pain have focused on impairments in how connective tissues connect to other tissues in the body, this project will use a new imaging technique to study myofascial tissue physical properties, including how they move in the body and their structural stiffness. This research will identify an imaging biomarker to be used in a randomized controlled clinical trial to predict patient responses to a myofascial pain 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:

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: 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:

 Chronic persistent post-operative pain (CPOP) is a devastating outcome from any type of surgical procedure. Its incidence is anywhere between 20-85% depending on the type of surgery, with thoracotomies showing one of the highest annual incidences of 30-60%. Given that millions of patients (approximately 23 million yearly based on incidence) are affected by CPOP, the results are increased direct medical costs, increased indirect medical costs due to decreased productivity, and associated negative effects on an individual’s physical functioning, psychological state, and quality of life. Given these extensive public health and economic consequences there is a resurgence of research in the area of preventative analgesia.  The goal of this project is to evaluate a novel small molecule antagonist of MD2-TLR4, DT-001 in preclinical models of surgical pain representative of persistent post-operative pain. In collaboration with University of California, San Diego, DT-001 will be evaluated for its ability to block the development of neuropathic pain states. These studies will evaluate dose escalating efficacy of DT001 in rats in formalin and spinal nerve injury (SNI) models using both intrathecal and intravenous routes of administration. Tissues will be preserved to assess functional effects on relevant pain centers for analysis by Raft. With demonstration of efficacy, these studies will determine the optimal dose and route of administration of DT001 and guide a development path to IND and eventually clinical trials.

NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-19-021
Summary:

Chronic pain is common, costly, and debilitating. Opioid prescription in the treatment of chronic pain is frequent and carries a consequent risk of poor treatment outcome, as well as higher morbidity and mortality in a clinically significant number of patients, particularly those who meet criteria for opioid dependence. Despite the alarming increases in prescription opiate misuse and opioid use disorder (OUD) nationally in the United States, there are few treatment options available that target both pain-related interference and OUD among patients with chronic pain. In military veterans, this issue is of particular importance as numerous reports indicate frequent use of opioids in the treatment of chronic pain, as well as increasing opioid-related problems. To date, there are no evidence-based treatment options that aim to both reduce pain interference while simultaneously addressing problematic opioid use. The overall aim of this study will be to determine the efficacy of an integrated psychosocial treatment in veterans with chronic pain who are taking buprenorphine for the treatment of OUD. To achieve this aim, they will utilize a randomized design to assess the efficacy of two empirically supported interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness-Based Relapse Prevention for substance use and misuse.

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:

G-protein coupled receptor 3 (GPR3) is an orphan receptor present in the central nervous system (CNS) that plays important role in many normal physiological functions and is involved in a variety of pathological conditions. Although the brain chemical that activates this receptor has not been identified, work with GPR3 knockout mice has identified GPR3 as a novel drug target for several Central Nervous System (CNS) mediated diseases including neuropathic pain. However, despite the emerging behavioral implications of the GPR3 system, little is known about how GPR3 affects behavior due to the lack of potent and selective chemical probes that allow scientists to examine functioning of the receptor. Recently, two cannabinoid chemicals present in the cannabis plant were discovered as affecting GPR3. This study will modify the chemical structure of these compounds to increase their potency and selectivity so that they may be used as pharmacological tools to investigate the role of GPR3 in modulating pain. In addition, this project focuses on identifying new compounds that show promise for development into therapeutics for the treatment of pain.

NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

Cholecystokinin B receptor (CCKBR) is a molecule found in the brain that helps regulate anxiety and depression but also influences the development of tolerance to opioids. CCKBR levels are also increased in models of nerve injury-induced (neuropathic) pain. Therefore, targeting CCKBR may offer a new approach to treating neuropathic pain and the associated anxiety and depression. Researchers have developed mouse antibodies that can inactivate CCKBR. However, to be usable in humans without causing an immune response, these antibodies need to be modified to include more human sequences. This project will use a fragment of the CCKBR antibody, modify it with the addition of human antibody sequences, and then select the clones that bind most strongly and specifically to human CCKBR. These will then be tested in cell and animal models of neuropathic pain to identify the most promising candidates for further evaluation in humans.

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: Back Pain Consortium (BACPAC) Research Program: Phase 2 Clinical Trials (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-AR-19-029
Summary:

The chronic low back pain (cLBP) subgroup with comorbid depression or anxiety disorders, known as high negative affect (NA), needs better non-opioid, comprehensive pain treatment options. Data shows that the combination of antidepressants (AD) and fear avoidance physical therapy is more efficacious at improving pain, function, depression, and anxiety in cLBP patients with high NA than each treatment alone or a control condition. Research also finds that an enhanced fear avoidance rehabilitation protocol (EFAR; fear avoidance-based physical therapy, pain education, and motivational messaging) further improves outcomes. To address the unmet needs of cLBP patients with high NA, this study will test in a randomized trial whether the combination of AD and EFAR is more effective than each treatment alone at relieving pain, improving function, combating depression, and preventing opioid misuse. This multimodal combination approach of pharmacotherapy and behavioral therapy is novel to the field and has the potential to shift current treatment paradigms.

NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-20-028
Summary:

Approximately 20% of patients who undergo surgery develop chronic Postsurgical Pain, which is linked with slow recovery, persistent opioid use and dependence. This project supports a scientist from a group underrepresented in biomedicine to expand ongoing research testing ketamine during and/or after surgery to prevent post-mastectomy pain syndrome. Ketamine is a low-risk treatment option that is easy to implement in a wide range of clinical settings.

NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-20-028
Summary:

Approximately 20% of patients who undergo surgery develop chronic pain, or Chronic Postsurgical Pain (CPSP). CPSP is highly associated with impaired functional recovery and persistent opioid use and dependence, and current standard postoperative multimodal analgesia is only moderately effective for its prevention. This study aims to determine whether the use of ketamine during and/or after surgery prevents Post-Mastectomy Pain Syndrome (PMPS), one of the most common CPSP conditions. Ketamine is a low-risk treatment option that is easy to implement in a wide range of clinical settings. If successful, this treatment could improve postoperative pain management in individuals undergoing mastectomy and help combat the opioid epidemic.

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:

The emergency department is an ideal venue to reach and intervene with adolescents and young adults at risk for opioid misuse, particularly as young adults may disconnect from primary care when transitioning out of care in pediatric settings. This study will evaluate the efficacy of interventions of varying type and intensity to prevent or reduce opioid misuse or opioid use disorder. The research leverages technology that is appealing to youth to facilitate intervention delivery by health coaches. In this study, adolescents and young adults in the emergency department screening positive for opioid use or misuse will be randomly assigned to one of four intervention conditions with outcomes measured at 4, 8, and 12 months. Technology-driven, scalable interventions delivered via health coaches allow for real-time tailoring to the rapidly changing opioid epidemic, with the potential to prevent an increase in opioid misuse among adolescents and young adults.  Black/African American youth are at increased risk for opioid and other substance use, but they often do not participate in research studies. As a result, it is not known how well prevention interventions work with Black/African American people. This supplement will focus on increasing participant diversity and inclusion by recruiting additional Black/African American participants for this ongoing randomized controlled study of technology-driven prevention interventions.

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 California Clinical and Translational Pain Research Consortium (CCTPRC) consists of four University of California academic medical centers with considerable experience in pain management clinical trials, phenotyping, and biomarker validation. The network will leverage solid existing Clinical and Translational Science Award (CTSA) resources to make clinical trial execution efficient and rapid. The hub will be located at the University of California, San Diego, with spokes located on the other three campuses to provide maximum flexibility, ready to accommodate studies in a variety of pain conditions and provide successful recruitment and high-quality data collection.

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 Required)
NOFO Number: PA-18-573
Summary:

 Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain (CP) in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of CP [25-28]. However, the most common NIBS methods, e.g., transcranial direct current stimulation, have shown limited, if any, efficacy in treating neuropathic pain. It has been postulated that limitations in conventional NIBS techniques’ focality, penetration, and targeting control limit their therapeutic efficacy . Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue . This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat CP in carpal tunnel syndrome (CTS), both as a lone treatment and in conjunction with physical therapy (PT). Investigators hypothesize ESStim can be provided synergistically with PT, as both can encourage plasticity-dependent changes which could maximally improve a CTS patient’s pain free mobility. In parallel with the CTS treatments, the team will build multivariate linear and generalized linear regression models to predict the CTS patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics. The computational work will be used to develop an optimized CTS ESStim dosing model.