By Stephani Sutherland

Despite significant progress in pain research during the molecular biology explosion around the turn of the 21st century, the development of new drugs to treat pain has remained slow.

A growing awareness of chronic pain as a widespread and critical health condition led to more efforts to treat it. But doctors had few tools available aside from opioid medications—which can cause significant side effects, are not effective or viable for everyone, and have become less available as a pain therapeutic following the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain.

In response, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-term (HEAL) Initiative, a massive research effort aimed at addressing both pain and addiction, in part by supporting the development of non-addictive pain treatments.

The vision: Accelerate therapeutic innovation

Leading up to HEAL’s introduction in 2018, Linda Porter, PhD, had been working to better coordinate NIH pain research, which occurs not at one particular institute but across many of the NIH’s 27 institutes and centers.

“There was a lot of advocacy and recognition that pain research needed to be done more globally across NIH, instead of at individual institutes, and that we needed bigger programs,” she says.

Porter—named director of the Office of Pain Policy and Planning at NIH’s National Institutes of Neurological Disorders and Stroke from its founding until the NIH’s reduction in force removed her position and others in 2025—worked with a group of leading pain researchers in 2017 to produce the Federal Pain Research Strategy, a Department of Health and Human Services initiative.

It offered a vision for what was needed in the coming years to advance pain research, and ultimately helped guide HEAL’s priorities.

Kathleen Sluka, PT, PhD, FAPTA, a pain researcher and professor at the University of Iowa, also worked on the federal strategy. She has since served as the investigator for several HEAL-funded research studies.

“The HEAL Initiative was designed to make advances quickly in pain science,” she explains.

The biggest hurdle? Large-scale clinical studies.

“What HEAL has done,” Sluka notes, “is put together resources and mechanisms to do these large-scale studies”—the scale at which real breakthroughs start to happen.

The approach: Transform pain research

From the start, the researchers spearheading HEAL’s efforts and priorities had certain targets in mind.

“We needed larger clinical studies to understand how the biological underpinnings of pain aligned with the biopsychosocial phenotypes,” Porter explains, referring to the ways patients experience pain in their lives.

They also identified a clear need for better pain measurement and assessment. One major focus of HEAL has been identifying biomarkers—objective measures of disease progression or treatment response. There are no reliable, consistent biomarkers known for pain, and multiple research programs have been aimed at pinpointing them.

New treatments were a salient priority as well. There was broad recognition that new pain drug development had stalled. HEAL sought to help fill that gap.

“For the last 50 years, we’ve had very few new pain medications,” says Sluka. “There’s a lot of barriers that stop a new pain drug from getting into practice”—such as the cost, both chronological and financial, of translating basic research discoveries into clinically viable compounds. “So the NIH developed an infrastructure to allow a basic researcher to take a target they think is viable all the way into human subjects, to test for safety and then show it has some efficacy.”

The hope is that pharmaceutical companies will then advance those compounds to the next stages. Several compounds and devices developed with HEAL funding are now in clinical trials.

Another feature of HEAL lauded by Sluka, a physical therapist, is its support for studies on non pharmaceutical pain treatments. In the past, there was little research to reinforce their use in pain treatment—but, she explains, “Now people recognize them as important.”

As a whole, Porter says, HEAL is championing individualized, multimodal care.

“We’re moving toward tailored medicine by finding and testing new treatments,” she shares. “And most of the clinical trials we ran also involved multidisciplinary care—it’s a big part of HEAL’s strategy to look at integrated care.”

THE FUTURE: HEAL’S STRATEGIC RESEARCH PRIORITIES

After seven years of HEAL funding, NIH leadership convened the HEAL Pain Strategic Research Priorities Working Group in 2024 to create a blueprint for the initiative’s future.

The group—which Sluka co-chaired with Robert Gereau, PhD, a pain researcher at Washington University Pain Center in St. Louis—invited experts in the field to strategize HEAL’s next steps. Seven subcommittees were formed, including in non-addictive pain therapeutics development, biomarkers and predictors, health equity and pain, research workforce and training, and more.

The groups held online public workshops in the fall of 2024 and settled on a series of 10 recommended research priorities. The recommendations hit a range of key aims, Sluka says, including identifying biomarkers, developing pain therapeutics, improving clinical practice, exploring multidisciplinary treatment, reducing the acute-to-chronic pain transition, and training pain researchers.

In addition to the recommendations, the committee also drafted a series of five core principles that should be embedded into any HEAL funded study, including utilizing interdisciplinary teams and educating providers and the public. The first principle: Include people with lived experience (PWLE) at every stage of research, from planning to implementation.

And that started with the strategic planning project itself. “We had PWLE as active participants through the entire process,” Sluka notes. “That helped us guide what would be important to individuals who are experiencing chronic pain.”

Learn more about HEAL: heal.nih.gov