The National Pain Strategy stood little chance.
The federally-funded, 17-part plan
to bolster systemic, evidence-based care for chronic pain in the US had many promising traits. It was goal-oriented, it was comprehensive, and it was dependent on measures proven to work for federal agencies.
But it competed with the opioid epidemic.
The plan was released in the same week of March 2016 as the US Centers for Disease Control and Prevention (CDC) guidelines for prescribing opioids in chronic pain. Discussion boomed around the latter; few gave attention to the former.
Strategy co-author Sean C. Mackey, MD, PhD, saw that coming from a mile away. When organizers told the Pain Medicine Division chief at Stanford that they would announce the plan around the same time as the new guidelines, he already knew which would catch headlines. He quipped to HCPLive®
the decision was simply a “strategic misfire”—but really, it was an issue he and colleagues are all too familiar with.
The pain medicine movement was struggling to progress in this century, hindered by what defined it in the century before.
“Here's the deal with the opioid crisis: like every other epidemic that we have faced in our country's history, we're going to address this problem, we're going to fix this problem,” Mackey said. “And then we're still going to be left with untold millions of people with chronic pain.”
Take the estimated 2.1 million Americans
with opioid use disorder (OUD). Add the approximate 950,000 annual heroin users in the US—for the sake of this exercise, assume they’ve all come from an opioid dependence.
Double that number. Double it again. And again. That number equals less than half of the Americans estimated to suffer from chronic pain.
Investigators like Mackey see modern pain medicine research branch off into two possible pursuits: to either seek means of reducing opioid dependence, or to seek efficient therapies that make their prescribed use redundant. Both are noble efforts; neither has been definitely accomplished.
But there’s some tangible hope in a handful of agents—and the general population has certainly endorsed lesser-regulated products cannabidiol and marijuana. But what may finally push pain medicine from a treatment void to a well-managed specialty is the combination of the right priority of drugs, the right care team, and the right system.
Old Agents Made New
Naltrexone has varying benefits in pain management. In fact, its use may cover both pursuits of the field: it can treat addiction and chronic pain.
The 57-year old oral opioid receptor antagonist was first approved by the US Food and Drug Administration (FDA) in 1984 for the treatment of opioid addiction. Generally taken as a 50 mg daily drug, naltrexone bears a similar structure and function to overdose therapy naloxone (Narcan), but has a greater oral bioavailability and longer biologic half-life.
What has interested Mackey and colleagues is low-dose naltrexone—a ≤5 mg dose of the longtime drug, which is showing in research
to have very effective and safe benefit for chronic pain.
“I'd say 30% to 40% of people respond well to it,” Mackey said. “And that's pretty typical of a lot of the drugs we have. But when people respond to this is, it's rather profound. And the nice thing is it has almost no side effects.”
The clinical benefits of low-dose naltrexone are also its hurdles in development. Because it’s a generic, it is cost-saving on prescribing. But it also has little to no monetary value among pharmacy companies as a generic, which limits research funding and makes it a near impossibility that a developer will pursue a new indication for it.
What’s more, Mackey envisions a more promising agent may deliver 50%, maybe even 60% efficacy on first use. Such a drug would align with the pain specialty’s hope for patient-tailored, precision medicines.
The diminished value of generic medications, as dictated by developers, is pitting researchers with another challenge in treating pain.
“We want to study 'new old drugs'—you know, repurposed drugs, that sometimes do not have a good incentive to do so, because there's not funding available,” Mackey said.
The Market Favorite
It’s likely impossible to name a product which has rejuvenated local US pharmacies like cannabidiol (CBD) has in recent years. More so than any other wonder pill, CBD has been widely touted for its so-called benefits across countless burdens and symptoms: anxiety, digestion, mood balance, appetite, and yes, chronic pain.
Its over-the-counter availability—from pharmacies to dispensaries and grocery stores—and generous marketing freedoms has driven its status as the next great replacement to the opioid pill. The collective CBD market is now projected to surpass $20 billion
in the US over the next 4 years. By large, the public is sold on its worth.
Mackey is not sold. As with medical marijuana, the basic science supporting CBD has not yet been backed by major clinical evidence. In some cases, the only available data is very conflicting.
“You find on one hand, well-controlled studies in laboratory situations showing benefit of cannabis in basic science models—and then even in some human neuropathic pain models. These are typically very short-term trials, carefully controlled laboratory conditions,” he said. “And yet on the other hand, we see more epidemiologic trials with larger populations where we show that it's not doing so well.”
Mackey also sees the boom of cannabis’ over-the-counter market as a hindrance to bettering research on its treatment of pain. The pharmacological push for thoughtful and thorough investigation is lessened when a non-prescription drug is embraced by consumers.
“Do I think that CBD is going to be the cure-all? No, absolutely not,” Mackey said. “If it were, we would be hearing reports from millions of people of how their pain has been fixed. And that's just not happening.”
Marijuana, at least, has been subjected to greater research effort. State-level trials are trying to establish a consistent benefit-risk portfolio, but Mackey is concerned that damage from legalization may already be done—especially among addiction-vulnerable patients.
Maybe, he prosed, cannabis proves to be curative—the true medical fix for pain. But maybe it doesn’t, and the pain crisis splits into a third branch of problems.
“There's only as a relatively small percentage of people on opioids that run into issues,” Mackey explained. “The vast majority of people are behaving themselves and doing fine. But when you start exposing huge numbers to opioids, you end up exposing a much larger number of that small percentage. And we may we may very well run into the same problem with cannabis.”
Putting Psych First
Beth Darnall, PhD, puts modern pain care into simple terms: treat it best, at the lowest risk. That strategy rejects opioids as the first option. It also stresses patient assessment—earlier, more extensively, and with an emphasis on treatment goals.
In a way, Darnall is practicing the traditional pain treatment plan in reverse.
Darnall, associate professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford, explained to HCPLive
that psychosocial care comes too late, if ever, for patients with pain. They’ve already exhausted their pharmacological options, have developed psychiatric burdens from their condition and care, and are now seeing a psychologist along with their specialist.
“At that point, what we’re treating is more their distress with the medical system and their experiences, rather than simply addressing the primary psychosocial dimensions of pain,” Darnall said.
Darnall and colleagues have found success in integrating psychology—namely, cognitive behavioral therapy (CBT)—to the very beginning of pain treatment. It makes sense: if there is no drug that’s evidently effective, safe, low-cost, and widely accessible, why would a prescription be the first response?
CBT, Darnall countered, has about 30 years of proven clinical benefit behind it. But its role is largely unrecognized by specialists, and its commitment is too great for the average chronic pain patient.
The “Empowered Relief
” program at Stanford, established by Darnall and colleagues, is a single-session, skills-based behavioral medicine class that condenses an eight-week CBT course into an afternoon. Patients with pain receive an education on their condition, interventions to improve their daily living, and they develop a personalized plan for pain relief by the class’ end.
What’s more, the class is not billed for insurance.
The program has quickly caught traction. A three-arm randomized control trial assessing the Empowered Relief pilot completes this year, and McGill University recently received a national grant to assess the effect of the program in primary care clinics throughout Canada.
Preliminary results from the 2020 trial show treatment groups reported a strong reduction of pain catastrophizing a 3 months post-care from eight-week CBT and a single session of the program. Citing its value as a didactic intervention, Darnall said a class in the program has effectively treated up to 85 patients and family members at a time.
“Pain is naturally distressing, and we're not naturally equipped with an understanding of how to modulate that,” she explained. “So that's what the class focuses on.”
Darnall insists the program is not designed nor capable of replacing long-course pain therapy. In fact, when used to inform patients on their condition, the language associated with pain treatment, and what can be accomplished with therapy, Empowered Relief could make pharmacologic care more effective—for swaths of patients all at once.
“We never put forward a concept that this in and of itself is going to be sufficient for everybody—but it is relevant and applicable to everybody, at minimum as a first step,” she explained. “For some people, that's really all they need—along with, of course, many other aspects of pain care.”
Indeed, education has been a long-overlooked gap in the chronic pain crisis.
Teaching the Patient to Treat
Robert Kerns, PhD, has had no choice but to treat pain as a major issue for all of his career. The professor of Psychiatry, Neurology, and Psychology at Yale School of Medicine and co-director of the NIH-DoD-VA Pain Management Collaboratory Coordinating Center has spent 4 decades treating and assessing one of the most comprehensively at-risk patient groups for pain: soldiers. Traumatic pain, acute pain, chronic pain, arthritis, psychological distress—the VA declared pain management a high priority for its patients in 1998. It was a high priority for Kerns and colleagues well before that.
It wasn’t until another 10 years from then that the Veteran’s Health Administration (VHA) launched the stepped-care model for pain management (SCM-PM)
, a strategy to ensure VA-based clinicians have full, consistent training of chronic pain management techniques that emphasize patient needs and expedient response to symptoms.
The National Institutes of Health (NIH) were among the fellow federal agencies that emulated the SCM-PM model at the time. From 2008 on, Kerns told HCPLive
, clinicians and organizations began to decrease pain medicine prescribing as they adopted similar models too.
“This broadly has transformed the way the practice of patient care occurs,” Kerns said.
But it’s up to the patient to seek out and trust these models of care. And what new pain patients generally have in common is little to no understanding of their condition. Kerns said patients struggle to manage and understand the actions of over-the-counter analgesics like acetaminophen and ibuprofen—how can they be expected to confidently manage drugs with even less clinical history, like CBD?
This situation—in which patients with chronic pain develop anxiety, and then desperation around treating their pain, while not learning more about their treatment—harbors public health crises like the opioid epidemic. Add to that equation a growing frustration around the limited access to actual evidence-based therapies in the current healthcare system, and the modern pain management strategy is in dire straits without better patient literacy.
“Whether we're talking about managing diabetes, heart disease or cancers, people are increasingly understanding the importance of our own behavior and our ability to make healthy choices versus poor choices that are health-damaging,” Kerns said. “Increasingly in the pain world, we're also trying to encourage that same way of thinking.”
As a psychologist, Kerns also advocates for a CBT-centric pain management plan. He noted patients have also had success from physical rehabilitation and exercises like yoga. But these strategies require a continued use to be beneficial—which means the patients improving are often the most disciplined and self-managed.
“That’s contrary to how many of us have grown up thinking about pain management,” Kerns said. “The emphasis is on learning to integrate some of these approaches into one's daily lives, as a way of more successfully ‘living with pain.’”
The VA is currently funding a large, multi-center trial that implements CBT via a web-based program that Kerns helped develop for chronic pain patients. The trial, which begins relatively soon, echoes similar to Darnall’s programs: CBT as the primary treatment, drugs and therapies as an add-on.
The makeup of these programs—which is distinguishable even in the National Pain Strategy—leads Darnall to believe we are finally in a renaissance of pain education: for the clinician, for the patient, for their family, for the future patient.
All that’s needed now is accessible, proven treatments, Darnall said—and a greater embrace of these strategies.
Since the strategic misfire of the National Pain Strategy, Mackey has spent time retooling its implementation. He understands what it lacked was a process that would drive its strategy goals, and first steps, into the public arena.
Irresponsible manufacturing, prescribing, and regulation led to mass addiction of opioids. That lead to greater heroin addiction, and that lead to greater synthetic drug addiction. Take the action that kick-started this epidemic decades ago, and you’re left with a national overdose body count of almost 430,000 in about 20 years. The OUD rates are about five-fold, and the overall numbers are likely still likely underreported.
Mackey hates that it’s such a tragedy like this that has drawn attention to his specialty, but he wants to make the most of it now that there’s a call for change. There’s greater opportunity for federal funding and more incentive to research non-opioids. And there’s greater reason for everyone to consider the value of team-based care while the pharmacological answers are sought.
In a way, the opioid guidelines overshadowing the pain strategy 4 years ago was a positive incident. While beginning to drum up fresh support for the plan, Mackey realized it’s more relevant now than it was in 2016. The opioid guidelines served to apply more regulated prescribing strategies, and emphasized the benefits of comprehensive pain management. The work of Darnall, Kerns, and others gained greater traction, and now the National Pain Strategy has a well-defined purpose and value among clinicians.
Because of the opioid epidemic, the public now understands the importance of properly treating pain. Mackey and colleagues now have the spotlight.
“My whole career has been about keeping my eye down the road, and seeing what the needs are in the future,” Mackey said. “And there's just such an overwhelming, clear, compelling need to address our pain problems.”