Finding a Signature for Chronic Pain Risk

About 3.5 million adolescents in the United States (and millions more globally) live with chronic musculoskeletal pain – but only about half find effective relief.

“A lot of teens are told that they have growing pains or that it’s something that they’ll just grow out of,” says pain psychologist Laura Simons, Ph.D., of Stanford University School of Medicine in Stanford, California. “But they don’t, and we don’t have a lot of good treatment options for them.”

That discomfort can interfere significantly with school, family, social interactions, sleep – and everything else that’s part of teen life. But Simons says many people don’t even realize that kids have chronic pain.

Simons’ research team, SPRINT: Signature for Pain Recovery IN Teens, is looking for a “pain signature” that will accurately predict persistent musculoskeletal pain – that is, teens with long-lasting pain in their bones, joints, muscles, and surrounding tissues. Funded by the National Institute of Neurological Disorders and Stroke via the Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®, the study explores what combination of characteristics lead to treatment-resistant musculoskeletal pain. Ultimately, the study team aims to provide a blueprint for guiding treatment.

That’s incredibly important, because without effective care, two-thirds of adolescents with chronic pain become adults with chronic pain.

The Care Journey

People of all ages living with chronic pain typically work their way through primary care providers, orthopedic specialists, rheumatologists, and sometimes even the emergency department before reaching a specialty pain clinic.

Adolescents who visit a specialty pain clinic include student athletes whose injuries just won’t heal, or those who get sick with the flu or other viral infection but don’t recover from the general tiredness and all-over body aches. Another group of teens with chronic pain is those with super flexible joints, a condition known as joint hypermobility. Having joints that are too loose can lead to frequent injuries and diffuse musculoskeletal pain.

The SPRINT team is gathering a huge amount of data from a few hundred adolescents with chronic musculoskeletal pain. That includes biological measures like functional and structural brain scans, fatigue and sleep health, sensitivity to touch and painful stimuli, and immune system activity, among other molecular data.

Simons’ team is also investigating how psychological and social factors affect treatment response in teens with chronic pain. These measures capture anxiety, depression, relationships with friends and peers, worries and fear of pain – as well as how much pain interferes with life. It’s important to capture this comprehensive set of information – biological, social, and psychological – because an individual’s pain experience is shaped by all these factors.

And while right now it’s not practical to perform routine brain scans or gather detailed molecular or behavioral information on individuals who visit a health care provider, the SPRINT research study hopes to identify the collection of factors (the signature) shared among teens at risk for treatment-resistant chronic musculoskeletal pain. Through further research, that signature may be simplified into a blood test or other non-invasive diagnostic strategy, Simons predicts.

“For example, we’ve discovered that one of the best measures for predicting knee pain is an individual’s change in sensitivity to a test where a mildly painful stimulus is repeated several times,” says Simons, further explaining that this measured level of sensitivity correlates with increased risk for knee pain. These simple procedures can lead to the development of clinical screening tools performed in a health care visit.

Beyond Pain Relief

For most adolescents Simons and her team talk to, pain relief is less important than function: the ability to live life the way you want to. In other, related research, Simons is conducting one-on-one interviews to learn more.

“We’ve talked to 44 families of adolescents with chronic musculoskeletal pain, asking them to walk us through their pain care journey and draw a timeline of it,” Simons explains, adding that often these individuals don’t view recovery as a main goal, but rather learning how to live with pain in a way that’s manageable for them.

Although pain has been less studied in children and adolescents, this approach is consistent with lots of research in adults with chronic pain. Psychologically guided pain management involves learning and practicing a range of coping skills that include guided relaxation, intentional distraction, and other approaches. HEAL research is currently evaluating how to increase use of these evidence-based strategies in adults and children.

Big Data and AI to Understand Pain in Teens

To generate an accurate, predictive signature for chronic musculoskeletal pain, Simons and her team are inputting thousands of data points that will be analyzed with artificial intelligence (AI) tools like machine learning. This is not her expertise, but she’s got plenty of help.

“The beautiful thing about this project is that we’ve been lucky to bring together some really brilliant people who have unique core skill sets to be sure everything is looked at properly rather than just at a surface level.”

The research is done in two phases: a “discovery” cohort of 152 youth and a “validation” cohort of 100. The first phase identifies all the components of a pain persistence signature, and in the next phase, the SPRINT team will see if the signature holds up in a different, unrelated group of adolescents with chronic musculoskeletal pain.

Even after the SPRINT study is complete, there’s a lot more to be done, Simons urges, explaining that the data they will have collected is from the largest cohort of adolescents with musculoskeletal pain to ever be collected to with this amount of detail.

“In my lifetime, I can’t answer all the questions that can be posed from this large dataset,” she notes, but HEAL has set up an easy way for others to use it.”

The HEAL Data Ecosystem provides a user-friendly infrastructure and centralized data management tools to help scientists maximize the investment in the SPRINT project and all of HEAL research. More shots on goal is key to solving the difficult problem of chronic pain – providing hope that children with chronic pain will not become adults with chronic pain.