George Mason researchers awarded $4.65 million NIH grant to explore chronic knee pain

For millions of Americans, chronic musculoskeletal pain is a daily reality that makes even simple activities like walking across a room, playing with grandchildren, or just getting through a workday feel daunting. At George Mason University, researchers at the Center for Advancing Systems Science and Bioengineering Innovation (CASSBI)are leading a new $4.65 million National Institutes of Health-funded R01 study to better understand what shapes those experiences, and how to improve care.

"Like many people all over the world, I have known close family members living with unexplained chronic pain," said the project's lead investigator Siddhartha Sikdar, professor of bioengineering and director of CASSBI. "I have seen firsthand how frustrating it can be to navigate a disjointed health care system that often does not prioritize patient voices. That's why I'm so excited about this project. It prioritizes understanding each person's lived experience of pain, so we can come up with better guidelines for personalized management of chronic pain."

Chronic musculoskeletal pain is one of the world's most common-and least understood-health conditions. It refers to ongoing pain in soft tissues of the neck, shoulders, back, hips, arms, or legs. Lower back and knee pain are leading causes of disability worldwide, disrupting work, family life, and well-being.

Despite its prevalence, the condition is poorly understood. Pain perception is difficult to measure, and each individual's experience of chronic pain is unique. Findings on currently available diagnostic tests paint an incomplete, and sometimes misleading, picture of the underlying problems. Too often, people with chronic musculoskeletal pain encounter fragmented care, misdiagnoses, or treatments that are expensive, invasive, and ineffective. Many report feeling dismissed or unheard.

The research team will work to solve this problem by studying how physical, biological, emotional, and social factors come together to shape the daily experience of living with chronic knee pain. They will look at whether analyzing multiple symptoms over time can help identify important turning points in a person's pain journey, and how each individual's particular mix of stress, biology, and movement plays a role in achieving maximal potential for function.

Over the next four years, the team will recruit participants with chronic knee pain who are receiving treatment at Optimal Motion, a community-based physical therapy clinic. For one year, participants will be followed closely, with data collected every three months on their biomechanics, physical function, biological health, and psychosocial well-being. A smartphone app will also allow participants to share daily reflections, giving researchers an unprecedented look into the lived experience of chronic pain.

"Chronic pain is not just about an abnormal finding in a single body part," Sikdar explained. "It's an individual, day-to-day experience that cuts across physical, emotional, and social dimensions."

Improving chronic pain management without overreliance on opioids and other medications with harmful side effects is a critical priority for addressing the ongoing public health crisis of opioid and other medication misuse, addiction, and overdose in America. Better understanding the factors that shape pain could lead to more effective personalized care and help reduce the devastating ripple effects of medication misuse and addiction.

This study is different from traditional pain research in three important ways. First, it uses a whole person focus. Instead of viewing knee pain only as a local problem in the joint, the team is taking a holistic approach that considers the entire person and the many factors influencing their pain. Second, it puts patient voices at the center. By using advances in large language models, researchers will analyze patient narratives, stories, and reflections, capturing rich perspectives often overlooked by conventional assessments. Third, it will track change over time. Rather than relying only on one-time snapshots, the study will follow patients' pain experiences as they shift from day to day and month to month.

The interdisciplinary project will involve medical scientists, community-based medical professionals, engineers, data scientists, neuroscientists, and CASSBI's chronic pain advisory board of patient advocates and community-based practitioners. George Mason faculty collaborators include:

• Kevin Lybarger, assistant professor, Department of Information Sciences and Technology, College of Engineering and Computing (expertise: artificial intelligence, natural language processing)
• Secili DeStefano, adjunct faculty, Department of Health Administration and Policy, College of Public Health (expertise: physical therapy)
• William Rosenberger, Distinguished University Professor, Department of Statistics, College of Engineering and Computing (expertise: statistics)
• Seiyon (Ben) Lee, assistant professor, Department of Statistics, College of Engineering and Computing (expertise: statistical modeling of complex data)
• Samuel Acuña, research assistant professor, Institute for Digital Innovation, Office of Research, Innovation, and Economic Impact (expertise: rehabilitation engineering, human-centered product design)
• Cameron Nowzari, associate professor, Department of Electrical and Computer Engineering, College of Engineering and Computing (expertise: robotics)
• Lynn Gerber, MD, professor emerita, medical doctor, Inova Center for Integrated Research (expertise: rheumatology, internal medicine, rehabilitation)

The team is also partnering with the University of Wisconsin-Madison and community-based providers such as Optimal Motion.

The project supports NIH's interest in advancing the understanding of individual differences in pain with a whole person approach to personalized medicine. It also aligns closely with CASSBI's mission to bring together scientists, engineers, health care professionals, and community members to drive real-world medical innovation.

For more than a decade, George Mason researchers at CASSBI have been working across disciplines to better understand chronic pain and this new study builds on that legacy with fresh tools, new partnerships, and functional outcomes that reflect wha patients have expressed is important to them .

"Pain is a uniquely personal perception and experience," said Sikdar. "Our goal is to listen more closely, understand more fully, and translate those insights into better care guidelines and treatments. Ultimately, it's about helping people get back to living their lives."