September is Pain Awareness Month – an opportunity to reflect on our efforts to help the millions of Americans who suffer from chronic pain and to acknowledge that pain has cascading impacts on individuals, families, communities, and the nation. At the National Institute of Neurological Disorders and Stroke (NINDS), in collaboration with our partners across the National Institutes of Health (NIH), our programs support research at all levels - from basic science to therapy development to clinical research. This interconnected tripartite strategy is contributing to an explosion in basic pain science and enables the transition of discoveries in the lab to the development of effective new non-opioid treatments for specific pain conditions. Equally important is the testing of available pain management algorithms to determine those that optimize function for an individual. Many of these efforts are part of the NIH Helping to End Addiction Long-term Initiative®, or the NIH HEAL Initiative®, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis.
Our approach recognizes the multifaceted nature of pain, and the complex ways in which chronic pain affects so many aspects of one’s life. Now our clinical studies are designed and launched with this patient-centered approach in mind. We also have a special focus on pain in populations that have been traditionally underrepresented in research.
NINDS is supporting the discovery of novel analgesic through basic research aimed to identify potential targets for pain relief, as well as co-leading the HEAL Acute to Chronic Pain Signatures Program, which aims to identify biomarkers that predict one’s susceptibility to chronic pain after bodily injury. NINDS also co-leads the HEAL Preclinical Screening Platform for Pain, a program that provides infrastructure to assess the efficacy of potential pain therapies using animal studies. Other ongoing NINDS efforts are underway to identify and validate animal models that may be more predictive of the human conditions than traditional rodent pre-clinical models. For investigators from academia or biotech with a novel pain therapeutic target, NINDS co-leads several projects that facilitate the process of developing a means to engage that target and even to testing in early phase clinical trials. In addition, the HEAL Non-addictive Analgesic Therapeutics Development program is focused on accelerating the development of non-addictive pain therapeutics. This milestone-driven program provides grant support, but also provides access to resources for the steps required to obtain an investigational new drug (IND) approval from the Food and Drug Administration (FDA) and Phase I clinical testing. Since HEAL began awarding grant funding, two projects anticipate IND submission within the next 18-24 months, and one of these projects has already been licensed for commercial development as a treatment for neuropathic pain.
NINDS also co-leads the HEAL Early Phase Pain Investigation Clinical Network (EPPIC-Net), which provides infrastructure to perform Phase 2 trials on promising pain therapeutics, supporting analgesic development from target identification all the way to efficacy research. Since EPPIC-Net opened to applications in 2019, three clinical trials have been funded, two with unique novel pain therapeutics and one with a re-purposed drug.
Other promising clinical efforts are also underway. For example, the HEAL Back Pain Consortium (BACPAC) research program led by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) began as a translational, patient-centered effort to address the need for effective and personalized therapies for chronic low back pain (cLBP). Its initial goals were to develop a state-of-the-art model for cLBP, identify factors to predict treatment effectiveness for well-defined patient subpopulations, and conduct a large-scale collaborative clinical study to inform an algorithm for multi-modal interventions for people with cLBP. I’m grateful to share that after NIH investments of over $130 million, the clinical trials for BACPAC are now beginning, and they represent an important step in achieving the NIH HEAL Initiative’s patient-centered goals.
With a patient-centered approach in mind, the NIH Pain Consortium held its seventeenth annual symposium this past June, titled Pain Management through the Lens of Whole Person Health. The meeting’s theme acknowledged how the complexity of pain management and treatment warrants consideration of multiple factors beyond separate organs and body systems and recognizes the interconnected nature of multiple biological, behavioral, social, and environmental factors. The symposium featured speakers from the research community and those living with pain conditions, with research presentations and discussions emphasizing the necessity of treating people for more than just their pain. The experience of pain is multifaceted and often overlaps with a host of other health conditions, increasing the complexity of pain management and treatment options.
HEAL Initiative studies have adopted innovative approaches to engage persons living with pain conditions. In fact, HEAL has provided supplemental resources to most of its clinical studies to enhance patient and community stakeholder engagement across the continuum of study design and planning, to outreach and recruitment of study participants, to continuity of study and health outcome goals beyond the duration of the project.
NINDS also recognizes that drivers of the complexity of pain may differ within an individual, across the population, differ among various populations, and be impacted by disparities in access to care. It is important to recognize needs of underrepresented groups and populations with few socioeconomic resources who have higher rates of chronic pain and co-morbid conditions and receive poorer pain care. The National Pain Strategy addresses the need to improve access to care for all people experiencing pain, and especially for those who currently are underserved by the medical community. NINDS is committed to broad efforts across biomedical research to address disparities in health care and outcomes, coordinated by our Office of Global Health and Health Disparities (OGHHD) within the Division of Clinical Research, including for pain conditions.
Progress and innovation depend on new voices and perspectives, and thus, it is essential that new researchers continue to join the field of pain research. The NIH Pain Consortium is working with HEAL to enhance the pain clinical research workforce through a multifaceted approach. HEAL now supports protected time for several experienced clinical pain researchers to mentor early career stage investigators, as well as diversity funding support to expand the field of pain researchers. In addition, HEAL will soon launch an effort that couples nationwide training and career development opportunities for early-stage investigators with a nationwide networking platform and opportunities for pain researchers to interact and learn from one another. The goal of these and other ongoing efforts is to create an enduring pipeline of highly trained pain researchers to meet NIH’s goals to improve pain management and develop effective non-opioid treatment options for pain conditions. To aid in the understanding of the NIH funding process and provide the opportunity for potential grantees to have their questions answered, the NIH Pain Consortium hosts a webinar series to provide the pain community with information on funding opportunities and resources provided by the NIH. All webinars are now available to view at the NIH Pain Consortium Website.
Throughout the month of September and beyond, it is important to remember that the dual crises of untreated pain and opioid use disorder and overdose are still with us. Every day in September and throughout the year, we in the NIH pain research community are striving to develop more effective treatments for the millions of Americans who suffer from chronic pain and other pain conditions. With strengthened attention to the multitude of factors that influence how individuals experience pain and through engagement with the pain community, we are hopeful for the progress we can achieve.