Funded Projects

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: RFA-TR-22-011
Summary:

Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain. 

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-042
Summary:

Chronic pain is maintained, in part, by persistent changes in sensory neurons, including a pathological increase in peptides derived from the neurosecretory protein VGF (non-acronymic). Preliminary findings show that the C-terminal VGF peptide, TLQP-62, contributes to spinal cord neuroplasticity and that TLQP-62 immunoneutralization attenuates established mechanical hypersensitivity in a traumatic nerve injury model of neuropathic pain. This project will test the hypothesis that spinal cord TLQP-62 signaling can be targeted for the development of new chronic pain treatments through immunoneutralization and/or receptor inhibition. It will pursue discovery and validation of TLQP-62-based therapeutic interventions along two parallel lines: identification of TLQP-62 receptor(s) and validation of anti-TLQP-62 antibodies as a potential biological therapeutic option for chronic neuropathic pain conditions.

NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
Summary:

Many individuals who receive medication-assisted therapy (MAT) leave treatment early and continue to struggle with opioid use disorder (OUD), often within the context of poorly managed comorbid chronic pain. Psychosocial interventions for pain have been effective in patients with chronic pain and substance use disorders, but these interventions have not been examined in the OUD population receiving MAT. This study proposes to refine and adapt a psychosocial pain management intervention (PPMI) delivered by telephone for patients with OUD receiving MAT and then to conduct a randomized controlled trial of the intervention in patients receiving MAT to improve adherence and pain- and substance-related outcomes. The intervention uses elements of cognitive behavioral pain management interventions adapted specifically for patients with OUD receiving MAT. The new intervention will be compared to an enhanced usual care condition (EUC) in 100 patients.

NOFO Title: Biology of the Temporomandibular Joint in Health and Disease (R01)
NOFO Number: PA-14-358
Summary:

Initial studies using positron emission tomography (PET) with [11C] carfentanil, a selective radiotracer for ?-opioid receptor (?OR), have demonstrated that there is a decrease in thalamic µOR availability (non-displaceable binding potential BPND) in the brains of TMD patients during masseteric pain compared to healthy controls. ?-opioid neurotransmission is arguably one of the mechanisms most centrally involved in pain regulation and experience. The main goals of our study are: first, to exploit the ?-opioidergic dysfunction in vivo in TMD patients compared to healthy controls; second, to determine whether 10 daily sessions of non-invasive and precise M1 HD-tDCS have a modulatory effect on clinical and experimental pain measures in TMD patients; and third, to investigate whether repetitive active M1 HD-tDCS induces/reverts ?OR BPND changes in the thalamus and other pain-related regions and whether those changes are correlated with TMD pain measures.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Promote Training in Clinical Research on Pain (Admin Supp ? Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-044
Summary:

There are numerous non-pharmacological interventions for chronic low back pain, yet no treatment is invariably effective for all. Understanding patient characteristics that predict differential responses to these non-pharmacological interventions will allow for tailored treatments to maximize positive patient impact. This supplement supports a training experience for an individual in clinical pain research, including exploring differential response to psychotherapeutic interventions. The aim of the project is to provide an extensive systematic literature review examining baseline phenotypic factors that predict differential responsiveness to the some of the most commonly used psychotherapeutic interventions for chronic low back pain.

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: 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:

Chronic overlapping pain conditions represent up to half of all chronic pain cases and can be more debilitating than other forms of chronic pain. These conditions include but are not limited to the following: temporomandibular disorders, fibromyalgia, irritable bowel syndrome, vulvodynia, interstitial cystitis/painful bladder syndrome, painful endometriosis, chronic tension type headache, migraine headache, chronic low back pain, and chronic fatigue syndrome. Common neurobiological mechanisms have been suspected to account for the overlap between these conditions, but until recently it has been difficult to efficiently classify each condition within individual patients. A digital classification tool for clinicians has been developed for this purpose, but access to the tool remains limited. Here we propose converting this chronic overlapping pain conditions classification tool into a common web-based application format.

NOFO Title: Research Project Grant (Parent R01)
NOFO Number: PA-13-302

NOFO Title: Mentored Research Scientist Development Award (Parent K01)
NOFO Number: PA-16-190
Summary:

Quality implementation of evidence-based programs (EBPs) in community settings for youth is critical for reducing the burden of alcohol, tobacco and other drug (ATOD) use and its consequences. EBPs delivered in schools are an efficient way to reach large populations of young people, including those underserved by other settings, and reduce and prevent ATOD use. Yet youth rarely receive EBPs as intended in community settings, including schools. This training and research plan will prepare the investigator to become an independent scholar in the implementation of theories and frameworks to better understand factors related to program delivery—approaches to enhancing ATOD programs for youth in community settings. More specifically, the training will allow him to expand the application of Consolidated Framework for Implementation Research (CFIR) to inform approaches to enhancing effective EBP delivery. The proposed training and research plan extends current implementation research to focus applying implementation theories, frameworks and strategies in other community settings (schools) and on economic evaluation of implementation strategies. The results are expected to improve current efforts to deliver EBPs in diverse community settings and aid in applying evidence-based implementation strategies in the school context to ultimately reduce and prevent ATOD use among youth.

NOFO Title: HEAL Initiative Limited Competition: Behavioral Research to Improve MAT: Ancillary Studies to Enhance Behavioral or Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-AT-19-007
Summary:

Chronic pain may be linked to poorer outcomes in those using medication-assisted treatments (MAT) to treat opioid use disorders (OUD). Psychosocial interventions for pain have been effective in patients with chronic pain and substance use disorders, but these interventions have not been thoroughly examined in the OUD population receiving MAT. The study team previously refined and adapted a psychosocial pain management intervention (PPMI) to be delivered by telephone for patients with OUD receiving MAT. The current study will understand the potential applicability of this intervention to other high-risk groups, such as veterans, study the longer-term impact of PPMI, and gather data to inform the implementation of PPMI in MAT patients. This work will provide a robust test of the PPMI intervention to help enhance MAT outcomes in a larger and more representative group of participants while also paving the way for future implementation of interventions to improve MAT retention.

NOFO Title: HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)
NOFO Number: DA22-047
Summary:

Little is known about what motivates people to use multiple drugs. Understanding these factors is important for tailoring treatment services. Behavioral economic theory, which determines how much value individuals assign to drugs and potential negative consequences, provides a framework to understand the choices people make. This project will identify patterns, motivating factors, and long-term trajectories of opioid-involved polysubstance use behaviors and treatment. This research will use a range of methods to analyze substance use episodes as well as examine motives and preferences associated with polysubstance use behaviors and how they change over time. The findings will be combined into a toolkit to inform timing, type, and tailoring of interventions and policies to guide implementation of effective clinical strategies and policies for managing polysubstance use in healthcare systems.

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

A persistent problem in the dissemination of medications for opioid use disorder (MOUD) is patient dropout, and matching patients to suitable medication early has the potential to minimize dropout. The overall objective of this secondary data analysis study is to develop and disseminate individual level risk prediction models using harmonized data collected from three multi-site clinical trials from the CTN, in order to predict specific clinical outcomes (e.g., dropout, relapse) for patients treated with MOUD, including methadone, buprenorphine or extended-release depot naltrexone. The relative importance of predictors in the best predictive models will be estimated, which may facilitate refinement of common data elements for future OUD studies. The comprehensive, harmonized database of treatment data created in this study can be used for future secondary data analysis studies and will provide a replicable data pipeline to process and validate OUD data in future protocols.