A Strategy to Shape the HEAL Initiative’s Future

The National Institutes of Health is taking an all-hands-on-deck approach to guide where the HEAL initiative to advance pain research and treatment should go next.

The opioid crisis in the US had been building for two decades, spurred by the overprescribing of drugs like OxyContin beginning around the turn of the century. To manage this growing public health emergency, the National Institutes of Health (NIH) launched a new program, the Helping to End Addiction Long-term^® (HEAL) Initiative in 2018. This endeavor had two main goals: To fund research that advances the understanding, management, and treatment of pain; and to advance solutions for the opioid overdose epidemic based on that research.

“We’ve been focused on reducing pain and finding ways to develop safe and effective treatments and prevention strategies to reduce chronic pain burden,” said Kathleen Sluka, a pain researcher at the University of Iowa, Iowa City, US, and co-chair of the HEAL Pain Strategic Research Priorities Working Group. “The idea is to propel the science forward so we can reduce the risk of opioids and improve the quality of life for people who live with pain.”

Now, since HEAL’s beginnings in 2018, with more than $3 billion in funding already distributed to support more than 1,800 research projects across every state in the US, NIH is building a roadmap for the future of this program. Having called for input from all stakeholders – including scientists, clinicians, advocates, and people with lived experience of pain –NIH will then take that information to develop a comprehensive set of strategic research priorities for the next phase of the project.

“This is a good time to assess how things are going, what HEAL has done well, what gaps may still be there, and what we can do to improve going forward,” said Robert Gereau, a pain researcher at Washington University in St. Louis, US, and co-chair of the Working Group. “We know there is always the opportunity to do better, and, at this moment, we want to hear from everyone touched by the opioid and pain crisis, so we understand what work we need to do in order to move the needle.”

The future of HEAL should be of great interest to migraine/headache researchers, considering that many investigators in the field have already received funding from HEAL and remain eligible for funding as HEAL takes its next steps. Pain research and migraine research have tended to progress on separate tracks, but as far as HEAL efforts are concerned, pain and migraine share the same umbrella.

HEAL’s accomplishments … so far
Since 2018, HEAL has funded a plethora of studies on opioid misuse and overdose, but also on preclinical, translational, and clinical research into pain management. Funded migraine and headache projects have included the development of a self-administered intranasal treatment targeting the trigeminal nerve, a drug-free nerve block device using thermal modulation, and an antagonist of protease-activated receptor-2, a receptor whose activation has been linked to headache in preclinical models.

To date, one of the program’s greatest accomplishments has been to develop strong research support capabilities to streamline the discovery and development of new therapeutics, said Sluka. This includes help with clinical trials, as well as an ecosystem to share data so researchers do not have to reinvent the wheel whenever they start a new project.

“There’s a lot a researcher has to do to take a drug from development to market. We’ve developed a network to help them do that and help them test their interventions in the real world,” she said.

Michael Oshinsky, director of the National Institute of Neurological Disorders and Stroke (NINDS) Office of Preclinical Research, NIH, Bethesda, US, added that three new treatment candidates are now ready for clinical trials, which is a “tremendous” step forward. They include the protease-activated receptor-2 (PAR2) inhibitor, as well as drugs that target MNK, an enzyme whose signaling has been associated with pain, and another drug that inhibits an enzyme regulating the activity of a type of anti-inflammatory fatty acid.

“Are they over the finish line? No. But when you look back at five years of work and three drugs with little potential for misuse that can go to clinical trials – not to mention the more than 60 new potential targets that are now being validated for the treatment of pain – you can see we are making good progress,” he said.

Preparing a plan for the future
With such success already in hand, one might wonder why HEAL is developing strategic research priorities. To start, Sluka said, most research projects are funded in five-year increments, so this is a good time to reevaluate the program.

But there is also another reason. NIH, like all federal agencies, is required to follow the rules provided by the Federal Advisory Committee Act (FACA) when creating advisory committees and strategies for different projects. Because of the exigency of the opioid crisis when HEAL started, the program relied on the 2017 Federal Pain Research Strategy, a strategic plan for federal agencies and departments that support pain research. Now, however, HEAL needs to abide by FACA guidelines as it comes up with its next set of priorities.

“There was a tremendous amount of external input into the foundation of HEAL and its goals, including many listening sessions for determining gaps and opportunities for addressing the opioid epidemic from the standpoint of pain treatment and overdose,” said Oshinsky. “But it was not a formal strategic planning process because we were in a health crisis emergency. Now we are at a natural inflection point to look at the kind of science that came out of our original funding, whether the landscape has changed, and where we need to go from here.”

To that end, the HEAL Pain Strategic Research Priorities Working Group put out a public request for information last summer. It then took the information and set up seven subcommittees, independent of any specific pain-related condition, to delve further into research needs. Those subcommittees include ones on non-addictive pain therapeutics development, pain biomarkers and predictors, optimization of existing and novel interventions for pain, implementation and health services for pain, health equity and pain across the life course, the intersection of pain and substance use, and pain research workforce and training.

“Each subcommittee has added their own experts, from across the spectrum of stakeholders,” said Gereau. “And what’s happening now is that each subcommittee is charged with coming up with a handful of high-priority goals that they believe will be most important going forward.”

Sluka said that the subcommittees recently hosted a series of virtual workshops to help guide those recommendations, and all voices were welcome. People can also provide their feedback to the different subcommittees via email.

“I’ve learned, over the years, that putting a bunch of different people in a room and letting them hash it out can help you come up with bigger and better things,” she said. “You gain really good perspective to help probe where we need to go next.”

Once the information is collected from the workshops, as well as emails and other communications, each subcommittee will review all the feedback and consolidate it into three to five strategic priorities. Those priorities will go to the HEAL Pain Strategic Planning Executive Committee headed up by Sluka and Gereau. Upon review, those recommendations will then be presented to NIH in January to help it craft the next set of HEAL funding programs.

“What we hope is that everyone knows that we are listening,” said Gereau. “We are working on a rapid timeline so we can get the ground laid and everything is ready to go for fiscal year 2027.”

For his part, Oshinsky said he is excited about the guidance all of the stakeholder input will bring. He added that migraine researchers were some of the first to look beyond the mu-opioid receptor for pain treatments, and others can learn from their hard work, risk taking, and innovations. The newly developed strategic research priorities will help guide HEAL, ensuring that the initiative continues to innovate and advance the pain field as efficiently and effectively as possible.

“Once we understood that regular use of opioids made headache worse – medication overuse headache – the field moved away from opioids and opened up the possibility for triptans and CGRP drugs,” he said. “It was revolutionary, and we can use the headache field as a model for what we are trying to do across the rest of the chronic pain field.”

Kayt Sukel is a freelance writer based outside of Houston, Texas.

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