Predicting Pain

Investigating the roots of chronic pain

Chronic pain is a health crisis in the United States. It affects an estimated 50 million Americans and costs more than any other disease, both in economic terms—total cost of about $600 billion annually—and in human suffering. However, the reasons why chronic pain develops are poorly understood.

In 2019, the National Institutes of Health funded the AC2CPS Acute to Chronic Pain Signatures Consortium, a first-of-its-kind research initiative supported by TACC to investigate the biological characteristics underlying chronic pain. The study reached a significant milestone this year—it now has more than 1,000 brain images to evaluate. In total, the initiative will evaluate 2,800 participants up to six months following surgery.

The initiative is the most comprehensive study to date to investigate the connections of peripheral biology, brain, psychological, and bio-behavioral risk factors. A project of this magnitude includes biologists, clinicians, pain neuroscientists, geneticists, and data scientists—and at the heart of the study is the individual who suffers with life-interrupting pain.

“Why do some people get better and others don’t? Ours is a first step where we can make a definitive statement and share the results with the pain community.”

Echocardiograms and cardiac biochemical markers are routinely used to diagnose heart disease; diabetes can be diagnosed with plasma glucose tests; and imaging is routinely used to help diagnose stroke and cancer. Viewed in this light, the need for biomarkers is especially crucial in pain research.

“Biomarkers are commonly used in many fields of medicine, but no validated biomarkers exist yet for chronic pain,” said Kathleen Sluka, a principal investigator in the Clinical Coordinating Center at the University of Iowa. “We’re evaluating 38 biomarkers in one sample set, which has never been done before.”  

The study is researching two types of participants— those undergoing knee replacement surgery with previous chronic arthritis pain, and those undergoing thoracic or cardio thoracic surgery who do not have pre-existing chronic pain.

“A lot of what’s happening with chronic pain involves changes in the central nervous system,” said Tor Wager, co-principal investigator at Dartmouth College. 

“We can measure those changes directly with structural brain imaging to look at the grey matter, and with functional brain imaging to see how the brain processes information and how brain areas connect to one another,” he explained. “We think these changes are going to be systematically related to the risk for future chronic pain and the incidence of chronic pain after surgery.”  

TACC provides the cyberinfrastructure and expertise that serves as the central nexus for information, data, analysis, and collaboration for the research initiative.

“A2CPS is a seminal study that will become a springboard for future studies of chronic pain and pain in general,” said Ari Kahn, Human Translation Genomics Coordinator at TACC and a co-principal investigator on the grant. “Our goal is to produce FAIR data, referring to a standard requiring that data be Findable, Accessible, Interoperable, and Reusable.”

The large sample size and comprehensive data collected over time give this study the credibility to predict who might be at risk. 

“Why do some people get better and others don’t?” Sluka asked. “Ours is a first step where we can make a definitive statement and share the results with the pain community.”

The A2CPS Consortium will be in the data collection period through 2026. Their paper published in the journal PAIN is titled, “Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.”