September is Pain Awareness Month and affords us an opportunity to recognize the burden of suffering and disability that people experience due to chronic pain. Scientists are helping to understand how best to treat chronic pain by mapping the cells and their connections in the brain and spinal cord that mediate “centralized pain” and identifying “peripheral” nervous system sensors that drive the sensation of pain. In 2021, two NIH grantees, David Julius, Ph.D., and Ardem Patapoutian, Ph.D., won the Nobel Prize in Physiology or Medicine for their discovery of receptors for temperature and touch, leading to new insights about the fundamental nature of pain and new targets for pain therapies. Scientific advancements like these that lead to a better understanding of the biological mechanisms of pain are crucial, but we also know that each person’s experience of pain is unique and shaped by multiple factors. The “biopsychosocial model of pain” takes a holistic look at how these factors, including biological, psychological (e.g., depression and anxiety; traumatic life events), and social (e.g., socioeconomic status; community relationships), interact to affect pain. By viewing pain and pain research through this lens, we increase the likelihood of finding successful interventions that can improve outcomes for the millions of people living with pain.
Pain research activities are broadly supported within and beyond NIH
Many NIH Institutes, Centers, and Offices (ICOs) support research within their missions that address pain, whether it be cancer pain, pelvic pain in women, pain due to musculoskeletal and skin disorders, dental-related pain, headache, abdominal pain, and more. NINDS works collaboratively with our fellow NIH ICOs to find better approaches to pain management. Key NIH-wide efforts to enhance pain research are supported by the NIH Pain Consortium and through the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®. The NIH Pain Consortium was re-established in 2003 to promote collaborative pain research efforts across 25 NIH ICOs. Launched in 2018 and led by the National Institute on Drug Abuse (NIDA) and NINDS, the NIH HEAL Initiative is resourced to speed scientific solutions to the overdose epidemic and the crisis of chronic pain. The NIH HEAL Initiative is pursuing targeted strategies to increase the development, testing, and accessibility of effective, non-addictive pain management strategies. Basic research supported by the NIH HEAL Initiative has led to approval for testing novel treatments for chronic and acute pain in humans, and the initiative is conducting large, collaborative clinical trials to find solutions for the treatment of common pain conditions. NIH HEAL Initiative pain research is supported and administered through a collaborative partnership of 15 NIH ICOs who are committed to improving pain care for all.
Over the past 10 years, the Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, or The BRAIN Initiative®, has funded the development of powerful tools to map, monitor, and modulate pain circuits in remarkably precise manners. NINDS and the National Institute of Mental Health are the lead Institutes among the 10 NIH ICs that participate in the NIH BRAIN Initiative. During this year’s BRAIN Conference, an individual with severe chronic musculoskeletal pain shared his journey with chronic pain before and after implantation with a closed loop brain stimulator. This is a device that detects brain signals that create a person’s perception of pain and then automatically triggers electrical stimulation of other brain regions that dampen the pain inducing signals. It provided remarkable relief of this person’s pain. The technology is helping us better understand the brain circuits that drive the perception of pain and those that can turn them off. It offers hope for those who experience severe pain that is not responsive to multiple pain management techniques.
Suffering due to chronic pain is a global health issue. To further promote collaboration that will advance the field of pain science, NIH, including the NIH Pain Consortium and NIH HEAL Initiative, teamed up with the IMI-PainCare Consortium in Europe to establish the INTEGRATE-Pain (IMI-NIH Transatlantic Emphasis Group on Research And Translation-to-care Efforts for Pain) Initiative. The goals of INTEGRATE-Pain are to facilitate and coordinate data collection and knowledge-sharing in research and clinical practice by using similar standards to collect pain relevant data and to share study findings broadly.
The voices of people who live with pain are crucial to advance meaningful pain research
Input and participation from people with lived experience of pain strengthens research, and NINDS includes individuals who bring that important perspective in workshops, roundtables, working groups, and committees as expert voices where they can directly inform research priorities. For example, the INTEGRATE-Pain Initiative gathered people with lived experience of pain, researchers, clinicians, and other interested groups to consider what biopsychosocial factors of the pain experience should be captured in research and clinical practice to make their findings meaningful to those who live with pain. A recently published paper describes recommendations for pain outcome measures that resulted from this activity. Incorporating all of these perspectives into this project has been crucial to its success in developing outcome measures that address different types of pain (acute, acute to chronic, recurrent/episodic, and chronic) and that are holistic in nature, covering biological, psychological, and social aspects of the pain experience.
Importantly, NIH has convened an external working group to develop pain research priorities for the next phase of the HEAL Initiative and the perspectives of people with lived experience of pain are a critical influence in this process. Earlier this year, the NIH HEAL Initiative sponsored a workshop on health equity in pain management that prominently featured input from individuals within communities experiencing health disparities. Stories from their experiences were important reminders that research data showing pain disparities are not just numbers–they represent real people facing systemic barriers in pain care. Findings from this workshop will be published soon. More recently, the 2024 NIH Pain Consortium Symposium focused on sex and gender differences in the biology, experience, and management of pain. The meeting underscored the value of people living with pain as partners in research and how they help to advance health equity in pain management. A panel of people with lived experience of pain emphasized that research partnerships are strongest when there is reciprocity and when researchers share their authentic selves in interactions.
Inequities within the pain experience
Beyond individual factors, systemic issues contribute to disparities in the experience and management of pain and health outcomes. For example, an individual’s pain story may be complex, unique, and influenced by unequal care associated with assigned sex at birth, gender, race/ethnicity, and/or socioeconomic status. The National Pain Strategy focuses on the need to improve access to care for all people living with pain, and NIH-funded research has sought to better understand the link between the effects of racism and other forms of social inequity on pain. NINDS is committed to efforts coordinated by our Office of Global Health and Health Disparities to address disparities related to care and outcomes for neurologic conditions, including pain, in projects that engage people with lived experience as research partners.
For example, many Tribal Nations have developed and continue to develop innovative approaches and systems of care for community members with substance use and pain disorders through culturally-grounded Indigenous knowledge. Despite the inherent strengths in Tribal communities, and driven in part by social determinants of health, Native American communities face unique health disparities related to the opioid crisis. In recent years, overdose death rates have been highest among American Indian and Alaska Native people. In response to this devastating inequity, in August, NIH launched the Native Collective Research Effort to Enhance Wellness (N CREW) Program to address overdose, substance use, mental health, and pain across Tribes and Native American communities. Led by NIDA, NINDS, and the National Center for Advancing Translational Sciences, N CREW aims to support Native American communities to conduct research prioritized by Native communities and to enhance research capacity by providing training, resources, and tools for research led by Tribes and Native American Serving Organizations.
Through these collective efforts and more, we look to build trust between researchers and communities experiencing pain disparities and advance health equity in pain management.
Involving people with lived experience to build and support the pain research workforce
We are continuing to grow and support the pain research workforce through unique perspectives in the research community. The Positively Uniting Researchers of Pain to Opine, Synthesize & Engage (PURPOSE) Network, an online career development network funded by the NIH HEAL Initiative, held its second annual meeting in May 2024. PURPOSE provides a collaborative space online for pain researchers and people with lived experience to learn about career opportunities, new funding opportunities, and upcoming meetings and events. It also facilitates peer-to-peer networking and ongoing training and educational activities.
In addition, the NIH HEAL Initiative continues to build the next generation of pain researchers through its National K12 Clinical Pain Career Development Award. This program, administered by the Chronic Pain and Fatigue Research Center at the University of Michigan, is designed to provide protected time for clinicians and scientists to focus on training in and conducting clinical pain research. A unique feature of this program is that people with lived experience serve as mentors to the K12 scholars. The 2025 Call for Applications was recently announced, and an informational webinar on the program was held on September 11, 2024. Letters of intent to apply are due on October 15, 2024.
Throughout Pain Awareness Month, we reflect on the progress made but also on the challenges that remain in addressing the continued crisis of chronic pain. Our commitment to listening to and incorporating the perspectives of people with lived experience communities as well as scientists and clinicians strengthens our ability to support meaningful research that can improve quality of life for everyone living with pain.