Funded Projects

Overreliance on opioids to treat chronic pain has been a contributor to the increase in individuals experiencing opioid addiction. This project aims to develop an innovative treatment approach for chronic pain that targets the cannabinoid receptor 1 (CB1R) to block the sensation of pain. The approach seeks to identify molecules that interact with a different part of the CBR1 receptor than do endocannabinoids and the primary active component of cannabis, tetrahydrocannabinol. Molecules that bind to and activate CBR1 in this different way (at an “allosteric” site) may produce nerve signaling that might differ from the effects of cannabis and endocannabinoids. This redirection of signaling pathways could help eliminate the risk of adverse effects observed with natural cannabinoids and other CBR1-binding molecules. The goal of this project is to identify a CB1R allosteric molecule, conduct studies toward obtaining federal permission to develop it as a medication, and to test it in a Phase I clinical study.

Many barriers exist in primary care offices where socioeconomically disadvantaged patients are most often treated. This project seeks to address chronic pain disparities that affect racially diverse, socioeconomically disadvantaged individuals. The study aims to optimize multimodal pain management in primary care clinics for low-income populations. This study includes two group-based models: integrative group medical visits and group acupuncture. These two interventions will be compared to typical treatment to measure both pain interference and social isolation. National experts and patient stakeholders will refine and optimize the design of the study with English- or Spanish-speaking patients with chronic pain in two primary care clinics for low-income populations.

Most people with opioid use disorder are either not in treatment or receive inconsistent treatment. Peer support is proven to be effective at engaging patients who are unwilling or unable to seek traditional treatment, but commonly available group support models are often separate from other clinical care or are otherwise hard for patients to access. This research will test a novel, machine learning enabled, digital peer support program added to an anonymous text-based social network that can provide 24/7 support for patients at all stages of recovery. The project will examine the ability of this digital service to engage and retain patients with opioid use disorder and will also develop novel techniques to automatically analyze patient messages for clinical and social determinants of health-related needs.

Currently available treatments for opioid use disorder (OUD) are insufficient for many patients. Novel compounds that can promote alterations in brain connections (i.e., neural plasticity) possess enormous potential for improving substance use disorder (SUD) treatments. Psychedelic compounds induce neural plasticity and can elicit long-lasting, beneficial impacts on a wide variety of SUDs. However, these compounds have significant side effects, including hallucinations and cardiotoxicity. Researchers have developed a novel, synthetic derivative of the psychedelic ibogaine, called tabernanthalog, that does not have these side effects. This compound has demonstrated both short- and long-term therapeutic effects in a preclinical model of OUD. This research study will determine the molecular and neural mechanisms through which tabernanthalog affects opioid seeking. It will also evaluate whether the effects are specific to opioids and do not alter response to natural rewards and will examine the efficacy of tabernanthalog in a preclinical model of comorbid opioid and alcohol use disorder.

Chronic pelvic pain is a debilitating condition that negatively affects the social and sexual quality of life for up to 20% of American women. Pelvic floor muscle (PFM) pain is caused by many factors, as well as by incorrect posture and excessive sensitization of the peripheral nervous system. This project will introduce a prototype of the Chronic Pelvic Pain (CPP) HomeTrainer that monitors, quantitatively and in real time, both PFM activation capacity and muscle interactions between the PFM and hip/trunk muscles and adapts the PFM training to the user’s needs in their own home. The proposed CPP HomeTrainer offers biofeedback to aid myofascial physical therapy and movement pattern training by tailoring the protocol to specifically correct interactions between the PFM and problematic hip/trunk muscles.

Both pain experience and treatment response are determined by a variety of factors, including race and ethnicity. Inequities in access to healthcare and pain treatment affect patients from minority populations, such as Hispanic/Latino populations of all age groups. This study will develop and test an online intervention—Web-based Tailored Intervention for Preparation of Parents and Children for Outpatient Surgery (L-WebTIPS)—tailored for Latino families of children having outpatient surgeries. The intervention aims to lower child and family anxiety before surgery as well as to reduce post-surgical pain by enhancing parent self-efficacy and behavioral pain coping strategies. After an exploratory phase to assess usability and acceptability of the intervention, the study will evaluate the impact of L-WebTIPS on child pre-surgery anxiety and post-surgery pain as well assess other child and parent outcomes.

Lumbar spinal surgery, an increasingly common surgery in adults with severe chronic back pain, is associated with acute post-surgical pain, costly postoperative opioid-related adverse effects, long hospital stays, high-risk for chronic post-surgical back pain, and persistent opioid use and dependence. Each individual responds differently to opioids based on their unique genetic and clinical factors, and the current trial-and-error approach to opioid use and prescribing promotes excessive opioid use, costly adverse outcomes, and poor surgical pain management. To address this issue, this research project will develop a preoperative diagnostic test that will use genetic and clinical information to proactively assess each person’s risk for opioid-related adverse events and chronic post-operative pain. The results will help clinicians provide personalized pain management to maximize pain relief while minimizing opioid-related safety risks, including opioid dependence.

There are significant and persistent gaps in knowledge about effective pain management for acute and chronic sickle cell pain. This is an area of relevant interest for the NIH HEAL Initiative's Early Phase Pain Investigation Clinical Network (EPPIC-Net). In order to provide guidance for hospital-based administration of the medication ketamine, this project will conduct a cross-sectional survey study of healthcare professionals within EPPIC-Net who provide care for people with sickle cell disease. This information can be used to design a clinical protocol for a multisite, randomized clinical trial of sub-anesthetic (low) doses of ketamine for challenging vaso-occlusive episodes (“pain crises”) in people with sickle cell disease.

This research project will investigate the cannabinoid receptor 2 protein (CB2R) as a novel therapeutic target for opioid-induced respiratory depression caused by fentanyl, oxycodone, and heroin. This study will shed light on how the endocannabinoid system in the brainstem works to control breathing under normal conditions and during opioid-induced respiratory depression. The research aims to determine whether activation of the CB2R with a brain-penetrant CB2R-binding molecule is safe and clinically useful for treating opioid overdose prevention and reversal. This research will pave the way for discovering new medications that activate CB2R to reduce opioid-related deaths.

There is a continued need to discover and validate new targets for potential therapeutic strategies for effective and safe treatment of pain. This project focuses on the protein metadherin, also known as astrocyte elevated gene-1 protein (AEG-1), as a possible new target for pain treatment. Preliminary studies have shown that mice genetically engineered to lack metadherin had significantly lower inflammation and chronic pain-related behaviors. This project aims to further validate AEG-1 as a pain target and test whether reducing levels in white blood cells called macrophages might work as a therapeutic strategy to reduce chronic inflammatory and/or neuropathic pain using an innovative nanoparticle approach to target specific cells.

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.

Pain is a common problem for people with end-stage renal disease that receive hemodialysis. Opioid use rates in this population are almost three times that of the general U.S. population over 65, putting them at significant risk for addiction. This research is testing treatments to manage chronic pain in this patient population. This project will develop educational materials to overcome barriers to telehealth toward enhancing research participation by American Indian/Alaska Native communities.