Purpose The purpose of this Funding Opportunity Announcement (FOA) aims to speed scientific solutions to stem the national opioid public health crisis by supporting the development of therapies and technologies directed at enhanced pain management through the Small Business Innovation Research (SBIR) program. Specifically, this FOA is focused on applications directed at improving pain measurement and treatment. Background This FOA is part of the NIH HEAL (Helping to End Addiction Long-term) Initiative—an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. More information about the HEAL Initiative is available at: https://heal.nih.gov. More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and lacks effective treatments. In recent decades, there has been an overreliance on opioids for chronic pain despite their poor ability to improve function. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative treatment options are thus critically needed. Research Objectives A. Scientific/Technical Scope Applications received under this FOA should have a primary focus on enhancing pain management, such as through measurement of pain-related outcomes. Applications must fall within the scope of the HEAL Initiative, including but not limited to: Tools and technologies to better understand the biological underpinnings of chronic pain, including new screening tools and models focused on pain and the development of pain therapies Discovery and pre-clinical development of non-addictive pain analgesic treatments with little or no addiction liability, including small molecules, biologicals, and devices Advancing new pain treatments with little or no addiction liability through the clinical pipeline Development of improved pain management strategies for acute and chronic pain conditions, including development of novel pain management technologies and devices, and objective pain measurement The following activities are not within scope of this FOA: Development of pain treatments with potential abuse liability, such as those targeting mu opioid mechanisms Methods to track or reduce opioid use other than through novel pain management solutions NIH-defined clinical trials to investigate novel pain management technologies While these activities are not within scope of this FOA, they may fall within scope of other funding opportunities through the HEAL Initiative and/or NIH STTR. For additional funding opportunities under the HEAL Initiative, please see: https://heal.nih.gov/funding/open. For additional funding opportunities under NIH STTR, please see: https://seed.nih.gov/small-business-funding/find-funding/sbir-sttr-funding-opportunities. The NIH clinical trial definition can be found here: https://grants.nih.gov/policy/clinical-trials/definition.htm. B. NIH Institute and Center Interests and Guidance National Institute of Neurological Disorders and Stroke (NINDS) The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The National Institute of Neurological Disorders and Stroke (NINDS) is interested in receiving applications directed at improving pain treatment, including the development of medications with little or no addiction liability, devices, and objective pain measurement. In addition, NINDS is interested in new screening tools and models focused specifically on pain and development of pain therapies. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) NIAMS supports research to develop therapies and technologies directed at enhanced pain management within the NIAMS mission. National Center for Complementary and Integrative Health (NCCIH) The National Center for Complementary and Integrative Health (NCCIH) will support research on development and optimization of technologies relevant to complementary and integrative health approaches and of nonpharmacological therapies for the management of acute or chronic pain conditions. Examples of research of interest relevant to this FOA include, but are not restricted to, natural products (e.g., herbs, prebiotic, probiotics, and selective medical diets), mind and body practices (e.g., acupuncture, meditation, manual therapies (e.g., spinal manipulation/mobilization), hypnosis, meditative movements (e.g. tai chi, yoga, etc.), music/art therapies, and whole person pain management (e.g. the development of sensory/diagnostic devices or applications that utilize Artificial Intelligence/Machine Learning (AI/ML) to elucidate the physiological, biological, and psychological mechanisms of multicomponent interventions on whole person pain management) National Institute on Minority Health and Health Disparities (NIMHD) Areas of interest: The mission of NIMHD is to lead, conduct and support scientific research to improve minority health and reduce health disparities. In the context of this FOA, NIMHD is interested in applications that focus on (but not limited to) the following areas: Addressing the intersection of chronic pain management and opioid use disorder (OUD): the development of therapeutic strategies and technologies that improve pain management and result in the enhanced continuity of care of patients with chronic pain. Conducting research/subgroup analyses to identify most effective therapies, technologies, and/or interventions at reducing the need for Opioid pharmacotherapy for specific populations, including the medically underserved and other health disparity populations. We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. National Institute of Biomedical Imaging and Bioengineering (NIBIB) The mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating engineering with the physical and life sciences to advance basic research and medical care. One way that this is achieved is through the support of research and development of new biomedical imaging and bioengineering tools and technologies to improve the prevention, detection, treatment, and monitoring of disease. NIBIB scientific program areas can be found at https://www.nibib.nih.gov/research-funding. NIBIB supports research from early stage technology development through first in human demonstrations and early feasibility clinical studies. National Institute of General Medical Sciences (NIGMS) NIGMS accepts applications directed at improving the treatment and management of pain in the peri-operative period, including the development of non-addictive drugs, devices and objectives measures of pain. NIGMS accepts applications on the development of strategies, methods, or new technologies to improve the delivery, monitoring, safety and efficacy of anesthesia. NIGMS also accepts applications relevant to pain management of burn injury. National Institute of Mental Health (NIMH) The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. For this FOA, the NIMH is interested in supporting the development of digital health technologies associated with pain and serious mental illness (SMI) or suicide, with the goal to reduce premature SMI mortality and to reduce suicide associated with pain and suffering. Examples of technology priorities within those specific goals include: automated, real time assessments of behavior in naturalistic environments, intervention refinement and delivery, and service delivery. Office of Research Infrastructure Programs (ORIP) The Office of Research Infrastructure Programs (ORIP) will support applications proposing relevant technologies to advance the determination, measurement, and/or amelioration/treatment of pain, using appropriate non-clinical models. National Institute of Dental and Craniofacial Research (NIDCR) The National Institute of Dental and Craniofacial Research (NIDCR) is interested in applications directed at improving diagnosis, management, and treatment of painful disorders of the orofacial region including temporomandibular joint disorders, trigeminal neuropathies, burning mouth syndrome, oral cancer pain, dental pain, and other conditions. Topics of interest include, but are not limited to, development of: new non-addictive medications, devices, technologies for objective pain measurement, screening tools and models focused on pain and development of pain therapies. Development of tools and technologies to better understand chronic orofacial pain conditions are also of interest to NIDCR. Investigators are encouraged to contact NIDCR program staff to discuss potential research projects prior to application submission to determine alignment of the planned studies with priorities of the Institute mission and strategic plan. National Center for Advancing Translational Sciences (NCATS) NCATS intends to fund applications that meet its mission. For a description of the NCATS SBIR/STTR research priorities see https://ncats.nih.gov/smallbusiness/priorities. National Library of Medicine (NLM) NLM intends to fund applications that meet its mission. For a description of the NLM SBIR/STTR research interest see https://www.nlm.nih.gov/ep/grantsbir.html National Institute of Nursing Research (NINR) NINR supports research programs that are developing and refining technologies to improve symptom risk assessment and identify potential interventions, promote health outcomes in diverse and underserved populations, and/or foster health, prevent illness, and improve health-related quality of life across the lifespan. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) NICHD is particularly interested in applications relevant to (a) persistent pain of women with endometriosis, chronic pelvic pain, vulvodynia/vestibulodynia, dysmenorrhea, and other gynecologic pain syndromes, (b) pain (acute and chronic) after minor and major surgical procedures, and (c) pain conditions (acute and chronic) in children, women of reproductive age, pregnant and lactating individuals, people with intellectual and physical disabilities, and health disparity populations (i.e. racial/ethnic groups, sexual and gender minorities, underserved rural and socioeconomically disadvantaged populations, people with limited English proficiency).