The Complexity of Pain Care

Does the HEAL Initiative Research Plan Misunderstand the Complexity of Pain Care? – By Richard A. Lawhern, PhD and Stephen E. Nadeau, MD May 3, 2019

This informative article carefully, and with published scientific evidence, explains why pain care with prescribed opioids is not the cause of the “opioid crisis”:

With relatively little public fanfare, the US National Institutes of Health (NIH) launched an integrated set of research initiatives, called Helping to End Addiction Long-term (HEAL), one year ago to “provide scientific solutions to the opioid crisis.”

Funding for this initiative was put into place for FY2019 at $502 million, of which approximately $170 million is focused on the discovery of biological markers to characterize acute and chronic pain as well as the development of non-opioid therapies.   

The federal government’s declaration of a public emergency around opioids in 2017 served as the impetus for HEAL, but the initiative touches only tangentially on the causes of the crisis.

One major component, for example, is the illicit use of heroin admixed with fentanyl, costing tens of thousands of lives a year. These deaths are born out of a series of complex factors, including

  • the growth of hard pockets of poverty,
  • hopelessness, and desperation;
  • failure to provide adequate care for the mental illness that looms large in most every addict’s life;
  • the enormous profitability of opioid sales (whether licit or illicit); and variously ill-conceived and mistimed public policy efforts.3

The 2016 CDC Guideline on Prescribing Opioids for Chronic Pain follows in this vein. Because the guideline did not remotely target the causes of the growing crisis, it could not have been expected to impact it — a prediction now confirmed by the ever-increasing tide of opioid-related deaths. The guideline succeeded only in creating a second crisis: a collapse of treatment for those living daily in moderate to severe chronic pain.

While the HEAL initiative contains a great deal of bold and scientifically inspired thinking, its rationale is contaminated with the unscientific precepts of the 2016 CDC guideline.

CDC assumptions were not based on good science and have been repudiated in multiple public and US agency forums, including the American Medical Association.

In fact, the CDC and FDA themselves recently issued major “clarifications” on the guideline and how rapid opioid discontinuation or tapers can actually be harmful to patients. See PPM’s editorial on this subject.

In the following sections, the authors offer their perspective and cautionary notes intended to support reconsideration of key directives within NIH’s HEAL Initiative Research Plan for the management of acute or chronic pain

The HEAL Initiative Research Plan: A Look at the Pain-Focused Elements

Enhancing Pain Management

The section of the HEAL initiative on enhancing pain management begins with the following assertion:

“Many of the 50 million Americans with chronic pain are prescribed opioid medications to manage their pain, yet there is limited evidence to suggest that long-term use of opioids is effective for patients with chronic pain.”

As pointed out in multiple published papers, authors of the guideline interpreted the paucity of long-term trials for opioid pain relievers as an indication that such therapies have not been shown to be effective. But under this criterion, none of the major categories of pain therapy considered in the guideline could have been proven effective.

Length of trials for both non-pharmacologic therapies and non-opioid analgesics have generally been limited to 90 days or less, and dropouts are frequent among chronic pain patients treated with placebo.

Further, the medical community now has multiple studies indicating that the annual case fatality rate attributable to prescription opioid dosage in excess of 100 MMED is on the order of 0.25%,8-10 a risk that most patients with moderate to severe chronic pain would likely deem acceptable

Deaths from prescription opioids have remained static since 2012.

Deaths from heroin and fentanyl have increased from 7,500 in 2012 to nearly 30,000 in 2017.

Furthermore, the demographics of opioid mortality clearly implicate two distinct populations: individuals over age 54 who are prescribed opioids two to three times as often as younger adults; and individuals aged 15 to 24.

Opioid overdose-related mortality in seniors is the lowest of any age group but overdose mortality in youth has skyrocketed over a period of 17 years to levels six times higher than in seniors.

This body of data is not reflected in the HEAL strategy rationale.

As noted by Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA):

“Unlike tolerance and physical dependence, addiction is not a predictable result of opioid prescribing.

Addiction occurs in only a small percentage of persons who are exposed to opioids — even among those with pre-existing vulnerabilities.”

Mental health receives relatively little attention in the HEAL document and socioeconomic factors are mentioned only in very narrow contexts. This is quite startling given that a major facet of the opioid crisis is almost entirely a street-drug crisis.

Street drug abuse commonly starts with non-medical use of diverted opioid tablets. However, multiple studies make clear that the risk of long-term opioid use in patients prescribed opioids for post-surgical pain is miniscule.

In a US 2018 study reported in the British Medical Journal, investigators examined outcomes among more than 586,000 patients prescribed opioids for the first time after surgery. Less than 1% continued renewing their prescriptions longer than 13 weeks; 0.6% were later diagnosed with opioid use disorder (OUD) during follow-up periods averaging 2.6 years.

Finally, a 2016 study reported in JAMA tracked long-term opioid prescription renewals in non-surgical patients and compared prescription rates to 642,000 patients who underwent one of 11 common types of surgery. Opioid prescriptions were defined as “chronic” when 10 or more scripts were written in 1 year or when a prescription was renewed continuously for more than 120 days. In this study, the rate for chronic prescriptions of opioid analgesics among millions of non-surgical patients was estimated at 0.136%.

Biological Underpinnings of Chronic Pain

It is well-accepted medical practice to titrate dosage to the desired level (eg, with antihypertensive medications, anticonvulsants, antidepressants, and innumerable other drug classes). This same approach seems to be a logical response to polymorphic variability in opioid metabolism but is not mentioned in the HEAL strategy.

“The Acute to Chronic Pain Signatures Program” is one research opportunity described in the HEAL plan.

…the Signatures program assumes that acute pain frequently evolves into chronic pain, whereas there is robust scientific evidence (some cited herein) that this is not the case.

There is no doubt that  post-operative pain may be improved. However, it is likely that in many if not most cases of those living in moderate to severe chronic pain, the pain evolved in the absence of an acute incident.

Establishing the Best Pain Management Strategies for Acute and Chronic Pain Conditions

In this section of the HEAL research plan, clinical trials on pain management effectiveness are discussed.

First, there needs to be a major emphasis on the development of innovative trial designs that will test opioids as they are optimally used in current clinical practice, and in particular, to accommodate adequate dose titration and the high incidence of idiosyncratic side effects

Of the nearly 100 published randomized controlled trials of opioids for chronic pain, only a handful come close to meeting these standards, all of them employing enriched enrollment randomized withdrawal (EERW) designs (see for instance, References 19-23).

Second, it is essential that non-opioid therapies be vetted through comparative effectiveness trials. It is highly unlikely that non-pharmacological and non-opioid drug treatments will be able to replace opioids in the near term for adequate treatment of moderate to severe chronic pain, although they may enable opioid dosage reduction

Overall Observations

The initiative’s short-term goals (ie, 3 to 5 years) focus on approaches and strategies while actionable results are not foreseen for 5 or more years.

In the meantime, the two opioid crises—the heroin and fentanyl crisis in the streets and the CDC 2016 manufactured crisis impacting patients living in moderate to severe chronic pain—will continue unabated.

More direct and immediate measures to combat these frontline problems need to be taken now, very likely through multiple agencies beyond the NIH.

13 thoughts on “The Complexity of Pain Care

  1. canarensis

    did my browser have some sort of seizure, or is there supposed to be a pre-filled-in (with my name & email address) comment section in the middle of the article? Duplicated? (it appeared just after the line “The section of the HEAL initiative on enhancing pain management begins with the following assertion:”
    I was rather startled to see my info as the assertion at the beginning of the HEAL section! I assume each reader gets their own personalized version. ;-)

    Now to the actual paper:
    “authors of the guideline interpreted the paucity of long-term trials for opioid pain relievers as an indication that such therapies have not been shown to be effective.” This has been nearly universally true, and I can’t help wondering if logic has been outlawed while my back was turned, or, like one of the old SF stories, the Earth passed through an outer space “stupid cloud.” How can these people, supposedly with some clue about science, medicine, & evidence, reach the conclusion “there isn’t much evidence to prove X, therefore X must be false”?? Again I imagine some post-doc presenting this “thinking” at one of my regular lab meetings, and again the only possible response I see them getting is extreme scorn & derision, accompanied by suggestions they go to Mickey D’s & get a job flogging fries, which clearly is all their mental faculties are fit for. They’d be very lucky if it wasn’t a lunch meeting or they’d be wearing food items.

    And another reason for the paucity of studies longer than 3 months is, it was considered unethical to subject participants to longer terms without pain relief…the dropout rate is already high among those receiving placebo even limiting to 3 months. (Yet this country –& especially Oregon– has no ethical qualms at all about forcing unwilling subjects into permanent withholding of pain meds; they won’t even do that to lab rats).

    “Signatures program assumes that acute pain frequently evolves into chronic pain…” The same BMJ article cited also repeats the fact that under-treating acute pain drastically increases the likelihood of it becoming chronic…so the program may be on the way to being correct in their assumption, since this country is now dramatically increasing the number & percentage of acute pain becoming chronic by refusing to treat the acute pain appropriately. Despite robust evidence that much chronic pain occurs in the absence of a precipitating injury, we’re in the process of conducting an involuntary experiment upon millions that will likely change that trend by deliberately creating a huge new population of chronic pain victims.

    ‘Best medical care in the world,’ my ass. I have a neighbor who’s a prime candidate for someone who’ll never again take a breath without agony due to the US Culture of Sadism. Surgery without adequate pain relief, then a blood clot in the lungs which is much more painful even than the original (fairly major) ab surgery, without pain relief. The person will be very, very lucky not to end up feeling like they’re being stabbed with a butcher knife with every breath they take for the rest of their lives. I’ve been in that situation since thoracic surgery in 2001 (with inadequate pain relief after), and I feel desperately sorry for this person and their kids who’ve gotten to watch their parent in agony for weeks. I pray they’re not one of the unlucky ones who ends up with acute pain turning chronic, but the setup is perfect.

    Liked by 2 people

    Reply
          1. canarensis

            I love to give folks a laugh! Glad ya got one.

            And well, (*ahem*) it feels great! I’d be happy to send you an autographed picture to brighten your life, for only (*cough cough*) a small fee. Sure to be a collectors’ item soon; you’ll get your money back & then some, I’m sure!

            Hopefully, that was good for at least a small smile ;-)

            Like

            Reply
  2. louisva

    Don’t you love REAL science? Science, until money comes into play, is the only thing I can think of that is self-correcting (more info and data)! I’m absolutely in love with the ‘scientific method.’

    Liked by 2 people

    Reply
    1. canarensis

      louisva;
      yep, been a science nerd forever. That’s part of what drives me so fricking crazy about this whole (successful) hysteria campaign; it’s absolutely AGAINST science & data & evidence & all that sort of thing. And $$$ is the only reason I can think of why such travesties of “studies” like the Krebs study & most of R Chou’s pathetic outputs get published…even formerly reputable scientific journals have jumped onto the hysteria/$$ train. To me, that’s blasphemy.

      Liked by 1 person

      Reply
  3. louisva

    I’m such a science nerd that I believe that humans and the opium poppy co-evolved. Why else would we have receptors to use the wonderful medicine it provides. Same with marijuana!

    Liked by 1 person

    Reply
    1. canarensis

      Hm, good point on the co-evolving. God knows, humans (& every other species on the planet) have been going after mind-altering substances since the first slime ran across a different slime that made it light-headed.

      Liked by 2 people

      Reply
      1. Zyp Czyk Post author

        Co-evolution is an interesting concept that seems to explain a great deal. I mentioned this back in ‘16 in a post about some NSAIDs leading to kidney cancer (https://edsinfo.wordpress.com/2016/07/13/nsaids-may-raise-risk-of-fatal-kidney-cancer/):

        Drugs that are concentrated versions of natural substances that have co-evolved with us (like aspirin, opioids, and cannabinoids) seem to be far less damaging, even over the long run, than those we chemically create to improve on the naturally-occurring version.

        Liked by 1 person

        Reply

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