By Rebecca McKinsey

With the prevalence of chronic pain in the United States—affecting at least 50 million people, 20 million of whom experience high-impact chronic pain that affects their day-to-day life and ability to work - and the challenges and cost inherent in treating it, a significant key is preventing it in the first place.

One major way to do so is to reduce the likelihood that acute pain will become chronic.

When someone experiences an injury or medical procedure that causes short-term, acute pain, what makes that person more likely than the next to experience long-term, chronic pain resulting from that acute incident?

The answer to that question could have massive implications—and it’s one that the National Institutes of Health (NIH) is seeking to answer.

Through its Acute to Chronic Pain Signatures (A2CPS) research initiative, NIH is seeking to identify “signatures,” or a series of characteristics or markers, that would make one person more likely to develop chronic pain stemming from the acute pain of an injury, surgery, or disease.

“In those who transition to chronic pain, maladaptive changes occur throughout the nervous system. Our ability to reverse these changes is very limited,” states information from NIH about the project. “Our lack of understanding of the mechanisms of transition to chronic pain is a major gap in knowledge that limits development of effective preventive therapies.”

With the identification of those signatures, people who are found to carry them in the future could receive targeted treatment plans immediately following an injury or acute event, and leading up to and following a surgery, to better treat the acute pain and reduce the likelihood that it would become chronic.

“This is so important, because chronic pain is both an individual problem, where some people’s lives are totally disrupted, and a population-level problem—which triggers an evaluation of what it costs the nation to treat people with chronic pain when we could have caught it earlier, treated them appropriately, and avoided it,” says Linda Porter, PhD, director of the Office of Pain Policy at NIH’s National Institute of Neurological Disorders and Stroke, and NIH staff co-lead for A2CPS. “This is a public health crisis. We need to address it.”

This is the first time a large-scale project focusing on chronic pain has been funded through the NIH Common Fund rather than on a smaller scale through an individual NIH institute, and it was approved now in part because of the opioid crisis and the need for better management of chronic pain, Porter notes.

“This project recognizes that chronic pain is a huge public health problem that needs to be served,” she says.

A project on a national scale

Across the United States, a consortium of researchers are collaborating on various aspects of the research initiative. They are studying two groups of people for six months or more: one having total knee arthroplasty surgery, or a knee replacement, and the other having thoracic surgery. The intent is to study about 2,800 patients in total.

These two procedures were selected because they’re relatively common, and there is a “high percentage of people, higher than it should be,” who go on to have chronic pain after these surgeries, Porter says. She notes that the study is examining two different procedures, rather than just one, in the hopes of finding parallels or differences in markers between the two, which could better indicate that the results would apply on a larger scale to multiple causes of acute-to-chronic pain.

Over the course of several months following each person’s surgery, the study will attempt to identify differences between people whose acute pain heals as it should, and those who continue to experience pain three to six months following the procedure—the typical length of time for pain to be considered chronic.

The study is taking place on a rolling basis, as additional participants are identified and their surgeries are scheduled. NIH is still seeking individuals to participate. The study will include individuals having surgery either at the University of Michigan, with sites across the state of Michigan, or Rush University in the Chicago metropolitan area.

‘Really cool science’

Dozens of markers in several key areas will be studied, including pain, function, disability, mood and affect, sleep, cognitive function, trauma, depression, anxiety, social support, as well as sensory testing that measures how various stimuli affect pain, and multiple characteristics measured through brain imaging and blood tests. Out of all the factors being examined, the study’s intent is to identify a smaller grouping of markers that together would best predict who is most likely to transition from acute to chronic pain.

“We don’t think any one single item will be the magic bullet—we think it’ll have to be a combination of things grouped together to actually predict who’ll transition to chronic pain,” explains Kathleen Sluka, PT, PhD, FAPTA, a professor of Physical Therapy and Rehabilitation Science and a principal investigator for the project at the University of Iowa, the A2CPS Clinical Coordinating Center.

At the Clinical Coordinating Center, one of the hubs around the country managing various aspects of the project, researchers help set, coordinate, and monitor processes to keep the data collection and clinical sites running smoothly.

“We’re all in this because of the really cool science,” Sluka says. “We want to see that data in the end, we want to see what’s going to happen with it, and we’re doing everything we can to get the highest-quality, best data we can with the most number of subjects in a timely manner.”

Far-reaching results

Part of what makes this project so groundbreaking is its scope—no other study has looked at this subject with as many biomarkers and as many clinical subjects.

“[Identifying key signatures] could lead to treatments that prevent people from getting chronic pain in the first place. As a society, that’s a good thing. People can just recover,” Sluka notes. “Take thoracic cancer—we cure it [with surgery] but then introduce a chronic pain condition that they’ll have forever. We want to prevent that altogether.”

A project of this scope has the ability to live far into the future, with the results of the study likely prompting novel treatments and additional, more targeted studies in the future, says Emine O. Bayman, PhD, an associate professor of Biostatistics and Anesthesia at the University of Iowa. She is working as a co-investigator on the project on a team that will create statistical models to analyze the extensive study results.

Bayman notes that the extensive list of markers being studied through A2CPS, and the resultant data, could feed into countless studies in the future.

“The [long-term implications of the study] excite me the most,” Bayman says. “So many patients have surgery every single day, everywhere in the world, and most of the time, after only several weeks, they’re back to their normal life. But then in some patients, that pain becomes persistent, months after their surgery. I think it will be really important to identify reasons why that group of participants ends up with long-term pain from that surgery, impacting their quality of life.”

In addition to the value to researchers and medical professionals, individual awareness of the project’s results will be an important aspect as well, Porter says.

“Not everyone in the world has access to good care, that’s a whole other issue,” she says. “But we want people to be aware that if you have an injury or have a surgery, it’s good to prepare and be aggressive—if it’s a self-management strategy, or if it’s a strategy that involves a group of providers. Public awareness will be important.”

The study’s authors hope that the results will help contribute to a greater understanding of the mechanisms of chronic pain, an important key to advocacy, research, and better treatment.

“Chronic pain is a biopsychosocial experience. It’s not one thing,” Porter says. “People who have chronic pain understand that, but the general public, not so much. That’s the word we’ve been trying to get out about chronic pain; it’s so important.”