Opioids for Chronic Aches & Pains

photo by Paul Ingraham

The notorious opioids come from the “milk of the poppy,”1 and have a reputation as the most potent pain-killers short of anaesthesia drugs. They include weak opioids like codeine (mostly found in small doses in Tylenol IIs and IIIs) and more infamous strong opioids: morphine derivatives and synthetics like Oxycontin, Percocet, and Fentanyl. They are all capable of inducing deep relaxation, euphoria, and making you “not care” about pain.2 All opioids are narcotics, but in health care we like to talk about “opioids” because it sounds better than “Let’s give you some narcotics for your chronic pain.”

But there are so many problems. We joke about “the good stuff” like it’s a given that it will do the job if anything will, but satisfaction is far from guaranteed.

• They don’t work at all or well for quite a few people for a variety of reasons, including genetic immunity.
• They are generally underwhelming for common kinds of body pain, and can actually backfire, which is nightmare fuel. However, they certainly can be effective for some chronic pain patients.
• It’s not even clear that opioids are effective for acute pain. Fun fact.
• And, of course, they are dangerously addictive. Extremely dangerous.
• In principle, narcotic pain killers have unlimited pain-killing potential (in contrast to the over-the-counter pain-killers, which can only relieve so much pain). But, in practice, taking too much will suppress consciousness and even life as well as pain.

But, as with cars and mountain climbing, some risks are worthwhile, and there is a vigorous ongoing debate about how opioids should be used, if at all. For each patient, it depends, and you need to talk to your doctor about it. And some doctors are far more qualified/willing to discuss it than others.3 This article is intended to help patients with chronic body pain prepare for that conversation.

Opioids for chronic musculoskeletal pain are probably mostly a bad idea (but it’s complicated)

Prescription opioid abuse is causing so many deaths by overdose that, in early 2016, the American Centers for Disease Control and Prevention (CDC) decided it had to do something. (Not the FDA, but the CDC!4) They made many recommendations, including that opioids should not be considered an option for chronic musculoskeletal pain,5 which were quickly adopted by many physician colleges around the world.6 I’ll get into the evidence more below.

The CDC’s position is strongly opposed by pain patient advocacy groups, because opioids obviously can help many people. Some kinds of patients do benefit from opioids, of course — more about this below. It is a disaster for those patients for opioids to be stigmatized and inaccessible!

The danger is real, though: it’s been called the “opioid crisis” repeatedly in recent years, because deaths from opioid overdose have tripled (in the US).7 In fact, since 2014, more Americans have died from opioid overdoses than from car accidents8 — the first time in decades that car accidents haven’t been the number one cause of accidental death.

And a whopping 60% of opioid-related deaths are linked to a chronic pain diagnosis9 — which is a huge problem for the argument that opioids are safer when prescribed for chronic pain.

We should probably stop thinking of opioids as “powerful” pain killers

As if all the extreme danger wasn’t bad enough, opioids just don’t work all terribly well for many patients. It’s not that they don’t work at all, just not nearly well enough or in the right ways for enough people to be very impressed by their “power.” As with all drugs, the effects are unpredictable at best. Some people are literally immune to (oral) opioids: they can’t get high that way at all!10 In a few people, they just straight-up backfire, a rare but nasty fate in which opioids actually start to cause more pain (“opioid hyperalgesia,” more on this shortly).

But recent scientific literature on opioid efficacy for many kinds of musculoskeletal pain is a litany of disappointing results:

• 2015 — A review of opioids for non-cancer musculoskeletal diseases concluded that opioids were “only slightly more effective than their placebos, no more effective than acetaminophen, and somewhat less effective than nonsteroidal anti-inflammatory drugs (NSAIDs).11
• 2015 — Friedman et al. Adding opioids to NSAIDs for acute back pain "did not improve functional outcomes or pain at 1-week follow-up."12
• 2016 — Shaheed et al. concluded that “opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important within guideline recommended doses.”13

• 2017 — A trial showed that regular pain-killers work just as well as lower-dose opioids for severe, acute extremity pain in the emergency room: “no statistically significant or clinically important differences in pain reduction at 2 hours.”14
• 2018 — Most relevant to most people, most of the time, a trial for patients with ordinary arthritis and back pain found that “treatment with opioids was not superior to treatment with nonopioid medication.” There were no important differences except that opioids have more side effects. A lot more.15
• 2021 — A huge review of common pain meds for arthritis concluded that the biggest loser was opioids: its modest benefit, “regardless of preparation or dose, does not outweigh the harm it might cause.”16 (The biggest winner, FWIW, was topical diclofenac.)
• 2023 — Daoust et al. reviewed opioids for post-ER usage and reported that “opioids do not seem to be more effective than nonopioid analgesics.” Importantly, they also clarified that by adding that “this absence of efficacy seems to be driven by codeine, as opioids other than codeine are more effective than nonopioids.” But still… probably not a lot more effective. And the failure of codeine is certainly notable in itself.17
• 2023 — The OPAL trial of opioids for moderate subacute back pain was negative on its face: "Opioids should not be recommended for acute non-specific low back pain or neck pain given that we found no significant difference in pain severity compared with placebo." (But it has also been strongly criticized, see sidebar below, Exhibit A: The trouble with the OPAL trial of opioids for back pain.)

All of this evidence suggests that opioids are surprisingly unimpressive as a pain treatment in general, and probably especially at safer dosages for many of the conditions people want them for. While they may well work better at higher dosages, then you’re flirting with greater addiction risk — and the stigma. The questionable efficacy should be a major point of concern when discussing the opioid option with a doctor.

What are the opioids? More detail

What are the opioids? Many opioids are household names, like the oxycodone brands Oxycontin and Percocet, the most popular narcotic painkillers in America for some time. Other familiar examples, some known better by the brand and others by their chemical names, are fentanyl (the drug that killed Prince), Vicodin (the one Dr. Greg House was addicted to), morphine, codeine (most widely available in Tylenol 2s and 3s), heroin and methadone, Demerol, and Darvon.

And, of course, there’s actual opium! Many famous people have infamous addictions to some of these drugs, such as Rush Limbaugh’s Oxycontin addiction.

photo by Paul Ingraham

Ripening seed head of an opium poppy.

“Opiate” is the older word referring specifically to poppy-derived compounds. “Opioid” refers to any drug with similar effects, opioid-ish, plus any pain-killing molecule the body produces itself. In practice, the terms are used imprecisely and opioid has been taking over. (Neither term includes the infamous benzodiazepines, better known as tranquilizers, like Valium.)

Weak versus strong opioids

The weak opioids are drugs like codeine, dihydrocodeine, and tramadol. The strong opioids are either morphine itself (the gold standard, the canonical opioid drug) or its derivatives and synthetic imitators like fentanyl, hydromorphone, methadone and oxycodone.

It seems like it would make sense to experiment with weak opioids before strong, but the weak ones are notoriously ineffective at lower doses, and when you increase the dose the efficacy doesn’t go up very much but you do get a lot more side effects! Bad deal. If you need any opioids, you probably need strong ones. If you don’t need strong opioids, weak ones aren’t worth it either. But that’s just an opinion, a starting place for a chat with your doctor.

Best prescription ever?

“Perco-Bull (Red Bull laced with perrcocett) [sic]… Side effects include but not limited to: Wings.” Source unknown.

Should opioids be demonized? Opioid phobia (especially in America)

The opioid crisis has led to extreme polarization and politicization of opioids, with patients largely caught in the middle. There are serious financial vested interests on both sides of the argument. In one corner, we have patient advocates fighting to protect access to opioids for chronic pain patients — but probably not all patient advocacy is altruistic, and there is cause to believe that some are being paid by the drug companies that are fighting to maintain their sales.18

In the other corner, there are anti-opioid players, some of them taking surprisingly extreme positions — and they too may be driven by surprisingly powerful vested interests.

In any case, demonizing an entire class of drugs is usually a bad idea. “Demonizing” requires oversimplification almost by definition. It might be justified and defensible to be “anti opioid,” given the serious dangers, but not everyone gets addicted and nothing is all bad. Opioids may still have a vital place in pain management for many kinds of patients, especially:

• severe acute pain (where there is an ongoing source of extreme “oh-shit” signalling from tissues)
• the terminally ill (where addiction and downregulation are not relevant)
• unusually severe/persistent pain where addiction is simply the lesser of evils, like some neuralgias or complex regional pain syndrome
• pain that cannot be treated with other kinds of analgesics for medical reasons

But there is still intense controversy about their use in any medical situation.

We certainly do need better evidence about opioids for severe, acute pain — that would be important even if they weren't such dangerous tools. But opioids aren't some silly alt-med or wellness whim, based on highly speculative biology mechanisms or wishful thinking and vitalistic nonsense. There is a compelling biological rationale for their judicious use, and I’d certainly prefer to have opioids for my severe, acute pain … even in the absence of evidence of efficacy.

Regardless of who’s right about what, it’s clear at least that there isn’t even consensus about using opioids for severe, acute pain. Many doctors now believe that the risk of addiction and other severe complications is just too great. Others — including many chronic pain specialists and patient advocacy groups like the American Pain foundation — believe that the risks of opioid addiction are exaggerated and the benefits of properly prescribed and monitored opioids are vital to many chronic pain patients. Some even argue that there’s essentially a tragic epidemic of treatable chronic pain going untreated because of ignorant prejudice against opioids.

For musculoskeletal pain in particular, over the last few years, expert opinion has shifted strongly towards the belief that they should only be used with great caution and close supervision … or not at all.21 But a lot of that opinion is dubiously based on trials like OPAL, which is obviously weak sauce.

How opioids can cause pain: opioid hyperalgeisa, and the insidious trap of “downregulation”

There are two distinct ways that opioids backfire:

1. Increased pain can be direct side effect of usage, a phenomenon known as “opioid hyperalgesia,” in which certain kinds of sensitivity ramp up while still taking the drug, for unclear reasons (very complex and poorly understood biochemistry).2223 This is a bit rare and exotic, and literally no one can explain it. We just don’t know what’s going on with these cases yet.
2. As an almost inevitable consequence of withdrawal from physiological dependence. This will happen to some degree to most people who take opioids, but you are shielded from it as long as you keep taking opioids. This phenomenon is powered by downregulation, which is a vital basic principle …

Nerves fire in response to specific chemicals. The number of receptors they have for specific chemicals is “regulated,” and they can be regulated “up” or “down.” If you flood a nerve with too much with a specific chemical, it will get “numb” to it — by downregulating the number of receptors for it. Clever system.

The opioid receptors are famous because they trigger the firing of nerves that inhibit pain. When you take opioids, you are washing those opiate receptors with many more opioid molecules than normal … and the body responds by getting rid of some receptors!

Downregulation of opiate receptors disables your pain inhibition system … and if you can’t inhibit pain, then you’re more sensitive to it. The trap has closed. The thing that killed pain has now made you more vulnerable to it.

The inexorable logic of downregulation applies to anything that tinkers with neurological signalling related to pain. It is a plague on the quest for a perfect pain killer, a fundamental reason why it may never happen. If you pick a pathway that inhibits pain, any pathway, give it a boost with some kind of artificial stimulation… gosh darn it if it doesn’t start downregulating and become less responsive to natural stimulation, et voila: you become either dependent on the artificial stimulation or seriously sensitized without it.

What if you’re already on opioids? Should you stop?

No one thinks these drugs are completely useless and dangerous for everyone all the time … just for so many people that it may be unwise to try them in the first place. All medical decisions are about balancing risk and benefit, and if you’ve already opened that door and walked through it, and there seems to be some real benefit and minimal risk in your case as far as you can tell so far… well then, phew. You’re one of the lucky ones: you’re demonstrating that opioids can be used safely.24

But please consider:

1. The benefits might be a least partially illusory. Opioids have that weird knack for making pain seem more tolerable — suffering reduction, rather than pain reduction. And suffering can be reduced in other ways. And maybe it should be.
2. The risks don’t go away just because you’ve been on the drug for a while and getting away with it. The risk of overdose continues. People can do just fine on opioids for a long time and then still get into trouble.

If you continue on opioids, work closely with your doctor and be wary of increasing your dosage, particularly if it has been stable for some time.

The smart way to ask for a opioids prescription

The rapid rise in “opioid phobia” comes with genuine and awful legal and ethical dilemmas for doctors and institutions, and arguably many of them aren’t handling it very well. Innocent patients who truly just want help are treated with great suspicion, like they are probably “drug seeking” — looking for a prescription to feed an addiction rather than to treat pain (which absolutely does happen). And of course such suspicion is likeliest with marginalized people. Guess who’s easiest to dismiss as a “drug seeker”? Weirdos! Wear a suit and tie to the ER or get treated like a criminal.

If you still want to dare to try opioids for your pain, find a doctor who respects opioids as a powerful tool to be used with great caution, if at all. And try the following

• Volunteer to accept only a low-dose prescription for a short period.
• Show that you understand the idea of dependence and the risks of addiction and death, and make it clear that you want supervision and collaboration.
• Ask for his or her opinion of what you should do.

Consider refusing a prescription from any doctor who does not show awareness of the risks — but those are getting rare these days, of course. If anything, the opposite problem is now looming: doctors are so hyper-aware of the issues that they don’t want to deal with opioids at all. And, in many cases, their hands are actually tied by policy.

It’s getting harder to find doctors that will help with getting off opioids

More and more chronic pain patients are “forced to navigate their transition off prescribed opioids, often with little or no assistance or guidance, with the potential for disastrous results,” explain the authors of a well-written NEJM editorial about the serious medical consequences of physicians choosing to “simplify their lives by discontinuing prescribing of opioid analgesics.”25

And why would physicians stop prescribing opioids? “The most important contributor to a desire to stop prescribing opioids is the effect of opioid prescribing on clinicians’ emotional well-being.”

Translation: dealing with opioids professionally is a huge bummer.

It’s difficult to walk into an exam room knowing that we have to significantly reduce or stop a patient’s opioid treatment — and then deal with the lengthy, emotional, possibly confrontational encounter that typically ensues.

“It’s difficult.” An understatement, I am sure.

Addiction versus dependence

Addiction is a loaded word, full of mischief. Like opioids themselves, it must be used with caution. It’s often used casually to refer to anything people overindulge in: chips, video games, shoes. But these terms have precise meanings that matter:

Addiction: Complex, compulsive, self-destructive behaviour driven by a craving.

Dependence: A relatively simple biological need for a drug, and immediate and significant medical consequences of deprivation.

And now with a little more feeling …

Physical dependence is the biological need for a drug to maintain normal function, caused by the drug itself, which does its damage only when the dosage is reduced. You can be dangerously dependent on a drug without knowing it, without being an “addict” at all (exactly the case for many people on opioids… and you can get addicted without dependence (gambling is the classic example). Importantly, physical dependence on a prescribed drug is always, by definition, an iatrogenic (doctor-caused) disease — doctors have an ethical responsibility to treat dependence regardless, but all the more so when they actually prescribed the drug that caused dependency.

Addiction is much messier than dependence: it’s a legitimate disease in its own right, but also a much more complex disease of self-destructively compulsive behaviour. It usually involves what most people think of as “psychological addiction.” The harm of addiction is mainly done by the behaviour, and addicts are routinely villified and personally equated with their disease.26

“Addiction” is such a powerfully stigmatizing concept that it undermines, dilutes, and distracts legitimate claims to physical dependence. When people are written-off as addicts, they often don’t get the medical care they obviously need for dependence. Or even just the damn sympathy.

For more information, see Is There Really a Difference Between Drug Addiction and Drug Dependence? [ScientificAmerican.com]

Related Reading

• Although the book predates the recent dramatic escalation in the opioid crisis, Marni Jackson explores the controversy with style in her book, Pain: The science and culture of why we hurt — a highly recommended read for anyone with chronic pain.
• “CDC issues guidelines against opioid prescriptions to treat chronic pain,” Susan Zalkind, TheGuardian.com. An excellent summary of the controversy around the CDC’s choice to do the FDA’s job and issue guidelines for opioid prescribing.
• “Five Studies: Understanding America’s Opioid Crisis,” Livia Gershon, PSMag.com. A good data-driven review of the prescription opioid addiction and overdose disaster unfolding around the world since the early 2000s.
• How risky are NSAIDS? A detailed review of anti-inflammatory medication safety, by pharmacist Scott Gavura.
• Planet Money Episode 711: Hooked on Heroin (17:38).
• PainSci guides to other kinds of pain medications:
  • The Science of Pain-Killers — A user’s guide to over-the-counter analgesics like acetaminophen, ibuprofen, and more
  • Voltaren Gel: Does It Work? — The science of the topical pain-killers, which can be effective without dosing your entire system
  • Vitamins, Minerals & Supplements for Pain & Healing — Critical analysis of most popular “nutraceuticals” — food-like pseudo-medicines taken for medicinal purposes, especially glucosamine and creatine, mostly as they relate to pain, arthritis, and recovery from exercise and injury
  • Does Epsom Salt Work? — The science and mythology of Epsom salt bathing for recovery from muscle pain, soreness, or injury
  • Marijuana for Pain — The hype versus the science! What does the evidence actually show about cannabis and chronic pain?
  • Vitamin D for Pain — Is it safe and reasonable for chronic pain patients to take higher doses of Vitamin D? And just how high is safe?
  • Does Arnica Gel Work for Pain? — A detailed review of popular homeopathic (diluted) herbal creams and gels like Traumeel, used for muscle pain, joint pain, sports injuries, bruising, and post-surgical inflammation
  • Homeopathy Schmomeopathy — Homeopathy is not a natural or herbal remedy: it’s a magical idea with no possible basis in reality
  • Muscle Relaxants — This topic is covered in several of my books in detail — low back pain, neck pain, trigger points, frozen shoulder, headaches. There is also condensed (but free) information about them in Cramps, Spasms, Tremors & Twitches.

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About Paul Ingraham

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter., or subscribe:

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Notes

1. Yes, that is a Game of Thrones reference. Throughout the books and show, the “milk of the poppy” comes up again and again, prescribed by the “maesters” of Westeros, always to horribly wounded and dying characters — of which there are quite a few, of course.
2. “Not caring” is a highly subjective and imprecise way of explaining an extremely complex phenomenon. Opioids don’t actually stop pain at the source. That is, information about tissue damage flows normally from your tissues to your central nervous system (with some possible exceptions). Mostly, opioids change how those warning signals are processed and interpreted in the brain. One way to put it is that they tinker with the perception of pain rather than the sensation of it, your pain tolerance, and your emotional and behavioural responses to pain — all subtly different things.
3. Ingraham. The Medical Blind Spot for Aches, Pains & Injuries: Most physicians are unqualified to care for many common pain and injury problems, especially the more stubborn and tricky ones. PainScience.com. 1387 words. Most doctors lack the skills and knowledge needed to care for common aches, pains, and injury problems, especially the chronic cases, which they tend to underestimate the complexity of. This has been shown by many studies, like Stockard et al., who found that 82% of medical graduates “failed to demonstrate basic competency in musculoskeletal medicine.” It’s just not their thing, and people with puzzling or stubborn pain should take their family doctor’s advice with a large grain of salt, and even lower their expectations of specialists (who tend to be too specialized).

   By all means, discuss opioids with your family physician — but it’s really the domain of specialists, preferably a doctor at a pain clinic, or any specialist who deals with a lot of chronic body pain (neurologists, rheumatologists).

4. The CDC usually leaves drug regulation to the Federal Drug Administration, but chose to issue their recommendations because of the rapidly increasing number of deaths from prescription opioids. They saw a dire need, and they stepped up. It was an interesting move.
5. CDC.gov [Internet]. Centers for Disease Control and Prevention. CDC Guideline for Prescribing Opioids for Chronic Pain; 2016 Apr [cited 16 Jun 22]. PainSci Bibliography 53446 ❐ “Plainly stated, the risks of opioids are addiction and death, and the benefits for chronic pain are often transient and generally unproven.” (CDC Director Tom Frieden, from March 2016 press briefing about the new guidelines). The FDA quickly responded with “enhanced warnings” about the “risks of misuse, abuse, addiction, overdose and death.”
6. For example, in Canada: “Physician regulatory colleges in four provinces, alarmed by Canada’s opioid epidemic and frustrated by a lack of federal action, are endorsing new national standards in the United States for prescribing painkillers” (Globe and Mail, May 8, 2016). In recent years, Canadian doctors have been prescribing more opioids than doctors anywhere else in the world.
7. PSMag.com [Internet]. Gershon L. Five Studies: Understanding America’s Opioid Crisis; 2016 July 27 [cited 16 Jul 29]. PainSci Bibliography 53301 ❐
8. National Safety Council: “Unintentional poisoning deaths in the adult population were not prevalent until the early 1990s. Since then this category has skyrocketed to 1st place, driven by unintentional drug overdose — predominantly from prescription painkillers.”
9. Olfson M, Wall M, Wang S, Crystal S, Blanco C. Service Use Preceding Opioid-Related Fatality. Am J Psychiatry. 2017 Nov:appiajp201717070808. PubMed 29179577 ❐
10. Tennant F. Why oral opioids may not be effective in a subset of chronic pain patients. Postgrad Med. 2016 Jan;128(1):18–22. PubMed 26635137 ❐

    We tend to think of opioids as potent drugs that are going to make pretty much anyone high, and therefore probably provide some pain relief … but there’s an incredible range of responses to drugs, even strong ones. This paper presents some specific reasons why some people just aren’t much affected by (oral) opioids: “there is a group of intractable pain patients who do not effectively metabolize oral opioids,” mainly because of gastrointestinal disorders and an inherited metabolic problem (cytochrome P450 enzymatic defects).

11. Berthelot JM, Darrieutort-Lafitte C, Le Goff B, Maugars Y. Strong opioids for noncancer pain due to musculoskeletal diseases: Not more effective than acetaminophen or NSAIDs. Joint Bone Spine. 2015 Oct. PubMed 26453108 ❐
12. Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015 Oct;314(15):1572–80. PubMed 26501533 ❐
13. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis. JAMA Intern Med. 2016 Jul;176(7):958–68. PubMed 27213267 ❐
14. Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial. JAMA. 2017 Nov;318(17):1661–1667. PubMed 29114833 ❐

    This JAMA trial showed that regular pain-killers work just as well for severe, acute pain. That certainly seems newsworthy.

    But nuance! Dosage matters, and this was a low dosage. Opioid effectiveness is strongly dependent on previous exposure, psychosocial factors, and genetics (see Tennant). These factors need to be considered. It’s likely that opioids are more effective for acute pain than this study suggests, for the right people with the right dose. (Hat tip to @DrJimEubanks for raising my awareness on this point.)

15. Krebs EE, Gravely A, Nugent S, et al. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018 Mar;319(9):872–882. PubMed 29509867 ❐
16. da Costa BR, Pereira TV, Saadat P, et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ. 2021 10;375:n2321. PubMed 34642179 ❐ PainSci Bibliography 52213 ❐
17. Daoust R, Paquet J, Marquis M, et al. Efficacy of prescribed opioids for acute pain after being discharged from the emergency department: A systematic review and meta-analysis. Acad Emerg Med. 2023 Dec;30(12):1253–1263. PubMed 37607265 ❐
18. TheGuardian.com [Internet]. Zalkind S. CDC issues guidelines against opioid prescriptions to treat chronic pain; 2016 July 27 [cited 16 Jul 29]. PainSci Bibliography 53306 ❐

    This article does a great job summarizing the controversy. Here’s a good excerpt:

    For Bob Twillman, executive director for the American Academy of Pain Management … the CDC’s move is an ominous sign that state and federal lawmakers will take increasing steps to turn CDC’s suggestions to prescribing doctors into a hard and fast rule. “It reflects a lack of experience in treating people with chronic pain,” says Twillman, who also receives funding from pharmaceutical companies.

    Kolodny, says the blacklash from pain advocates — many of whom are funded by pharmaceutical companies — is akin to naysayers of global warming. “It’s a manufactured controversy,” Kolodny says.

    So it’s quite contentious. Which is an understatement.

19. Jones CMP, Day RO, Koes BW, et al. Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial. Lancet. 2023 Jul;402(10398):304–312. PubMed 37392748 ❐

    The OPAL study was a 2023 Australian trial of a short course of slow-release opioids for subacute low back and neck pain of moderate severity. Three hundred people got either a placebo or an oxycodone/naloxone combo, plus standard care, for up to six weeks. There was no major difference in pain relief at the end of the test. The opioid group got more side effects, like constipation. The paper concludes:

    Opioids should not be recommended for acute non-specific low back pain or neck pain.

    Or as put by one of the authors on social media:

    The OPAL trial findings provide strong evidence that opioids should not be prescribed to people with acute back and/or neck pain.

    Is it really “strong” evidence for that, though? Many experts disagree. OPAL wasn’t all bad, of course, but there are two categories of legitimate concern about it:

    1. The science itself. There are legitimate concerns about OPAL’s design, especially whether they studied the right drug for the right patients. These were ignored by The Lancet for a year before they finally published three response letters.
    2. How the science was interpreted and presented. Namely, as if the results were much more broadly applicable than the evidence could actually support (even if they could be trusted, which they can’t, see concern 1.)

    Read a detailed blog post about the debate.

20. For instance, Dr. Maher, a prominent OPAL author, has blocked virtually all critics, and responded to my reporting like so:

    If we pretend that OPAL never happened, then you are left with no placebo controlled trials for acute spinal pain. The conclusion of OPAL still stands.

    But an absence of other evidence doesn't justify overconfidence in unpersuasive new evidence—that would undermine EBM long term.

    And other evidence isn’t entirely absent (“opioids other than codeine are more effective than nonopioids,” Daoust et al.). And opioids for severe acute pain also rest on other pillars of EBM: expertise, plausibility, compassion, patient prefs, and more. All of which should yield to strong contrary evidence, but only to strong evidence: not just one trial, not even a great one, and certainly not OPAL.

21. Pro Publica [Internet]. Ornstein C, Weber T. The Champion of Painkillers; 2012 Mar 7 [cited 15 May 23]. PainSci Bibliography 54413 ❐

    For years I assumed that narcotic pain killers are effective, and I took at face value the American Pain Foundation’s position that the risks of addiction are overblown, and the drugs are stigmatized and underused, resulting in a tragic lack of relief for many patients. This article casts reasonable doubt on all of that, and on the credibility of the APF, who may be serving the interests of pharmaceutical companies better than patients. In the spirit of Dr. Harriet Hall’s skeptical rule of thumb — “Who disagrees and why?” — it is clear that there is a problem here. Politics aside, I am most perturbed by the idea that opiates may not be all that effective in the first place. There is little doubt that these powerful drugs are valuable for some kinds of pain — just try passing a kidney stone without them! — but they may be surprisingly powerless against other kinds.

22. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–61. PubMed 21412369 ❐

    “Opioid induced hyperalgesia” is a nasty fate in which opioids actually cause pain instead of relieving it:

    Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli.

    Clinicians should suspect OIH when opioid treatment’s effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages.”

23. Grace PM, Strand KA, Galer EL, et al. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc Natl Acad Sci U S A. 2016 06;113(24):E3441–50. PubMed 27247388 ❐ PainSci Bibliography 53712 ❐

    This rat study demonstrated that opioids can actually cause chronic pain rather than treating it. In rats, anyway. Obviously replication in human studies is needed.

24. Huber E, Robinson RC, Noe CE, Van Ness O. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk. Healthcare (Basel). 2016;4(2). PubMed 27417617 ❐ “Harmful, dose-dependent deleterious effects have become clearer,” and yet “many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, ‘Who is at risk of opioid misuse?’ should evolve to, ‘Who may benefit from chronic opioid therapy?’”
25. Comerci Jr, Katzman J, Duhigg D. Controlling the Swing of the Opioid Pendulum. N Engl J Med. 2018 Feb;378(8):691–693. PubMed 29466151 ❐
26. Rather than addiction being seen as something that they have, like an illness, they “are” addicts — and addicts are bad people, failed people. In other words, they are blamed for it. It’s an understandable mistake, but a mistake nevertheless, and a tragic one.