“Opioid painkillers cause chronic pain” stories leave physician reader in agony

Steve_Martin_FinalThe following guest post is by Stephen Martin, MD, EdM, an Associate Professor of Family Medicine and Community Health at the University of Massachusetts Medical School. He’s also – along with Gary Schwitzer and several other editorial contributors – a member of the National Physician’s Alliance, a non-partisan, industry-independent group that works to provide affordable, high-quality health care for all people.


When writing in 1953 of the structure of deoxyribonucleic acid (DNA), Watson and Crick concluded: “It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material.”

Words like “postulated,” “suggests,” and “possible” seem quaint in 2016.  Instead, we have researchers and their accomplices in the news media who trumpet “game-changing” “breakthroughs” on daily basis – often with the flimsiest of scientific support.

The latest example: opioids causing pain

Consider the headlines generated this week by a study which documented a phenomenon known as opioid-induced hyperalgesia. This is the idea that opioid medication, instead of calming pain, might actually make pain worse.

Denver Post: CU Boulder study: Narcotic painkillers cause chronic pain

FOX News: Opioids may prolong chronic pain, study suggests

Washington Post: Opioid paradox: Could morphine use hurt as much as it helps by prolonging chronic pain?

Forbes: Prescription painkillers may worsen and lengthen chronic pain

Much has been made of opioid-induced hyperalgesia. Whether it is clinically important for patients with chronic pain on standard opioid medication is unclear. Even the most recent reviews of this phenomenon are unable to determine its prevalence (see here and here), and studies have generally been experimental in nature or with unusual administration of opioids (for example, the drugs have been administered intrathecally; that is, via direct injection close to the spinal cord).

A closer look at the study

lab assistant with laboratory ratsAs it so happens, the new Proceedings of the National Academy of Sciences study being reported on also involved intrathecal administration of medication.

Not only that, but the study also involved rats who had sutures tied around their sciatic nerves.

The sciatic nerve was tied and the animals were left in pain for 10 days. Then, the researchers administered morphine directly to spinal cords of these rodents for 5 days.

Their conclusion? “That morphine increased the vigor and speed of hindpaw withdrawal to the von Frey filaments in SD rats was supported by increased startle (converted to force; N) to a 0.2-mA shock.”

In other words, the rats that received the morphine showed increased sensitivity to a plastic “hair” and an electric shock.

Use of rat models to help elucidate human disease is nothing new. But use of rats to claim that the study’s “implications for people taking opioids like morphine, oxycodone and methadone are great, since we show the short-term decision to take such opioids can have devastating consequences of making pain worse and longer lasting” is nothing short of ridiculous and harmful.

A PR news release drives the narrative

That sensational quote, originating in the University of Colorado Boulder news release, was subsequently picked up by the Denver Post and a variety of other outlets that covered the story. While most of this coverage did acknowledge (in the body text of the story) that the study involved rodents, few stories pushed back against the researchers’ attempts to draw a straight line from this animal study to humans. Readers drew the same straight line: Of the over 300 reader comments on the Denver Post article alone, almost all are about humans, not rats.

Science magazine was one of those rare outlets that provided the perspective of an independent expert, who offered the following indispensable context:

The finding certainly shouldn’t be the basis for withholding opioids from people in pain, says Catherine Cahill, a neuroscientist at the University of California, Irvine. These drugs also work to block the emotional component of pain in the brain, she notes—a form of relief this study doesn’t account for. And opioids might not prolong pain in humans the way they did in these rats, she says, because the dosing of morphine and its quick cessation likely caused repeated withdrawal that can increase stress and inflammation. Humans usually don’t experience the same withdrawal because they take sustained-release formulations and taper off opioids gradually.

What’s more, none of the coverage that I saw tried to put this 5-day rat study into any appropriate historical perspective. Opium-derived products have been used to relieve pain since ancient times. Opium was one of the only medications not consigned to the bottom of the sea by Oliver Wendell Holmes in 1860. Morphine has been on the World Health Organization’s list of essential medicines since its inception. Yet opioids are not available to 5 billion people with consequent unmitigated pain and suffering. The American Geriatrics Society has determined opioids to be a potentially “indispensable” treatment for selected patients. British geriatric guidelines are similar. While advocating their judicious use, Canadian guidelines note that “opioids can be an effective treatment for chronic non-cancer pain (CNCP) and should be considered.”

Consider the CDC context

This rat study and the related coverage aren’t taking place in a vacuum. They’re taking place amid the CDC’s recent recommendations for the use of opioids in chronic pain — guidelines that excluded a Cochrane review showing effectiveness. The CDC took the acknowledged limited study in this area and interpreted it as evidence only of harm. Can harms happen with chronic opioid use? Yes. Can benefits also happen? Yes. By not acknowledging this dual truth, the CDC recommendations – and especially the rhetoric that has surrounded them (e.g. “prescription opioids are just as addictive as heroin”) – risk creating more heat than light.

This is in contrast to the National Institutes of Health 2014 report “Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain.” The report found that:

Patients, providers, and advocates all agree that there is a subset of patients for whom opioids are an effective treatment method for their chronic pain, and that limiting or denying access to opioids for these patients can be harmful.

Biased media reports on opioids also affect patients. Stories that focus on opioid misuse and fatalities related to opioid overdose may increase anxiety and fear among some stable, treated patients that their medications could be tapered or discontinued to “prevent addiction.”

The CDC guidelines also excluded acute pain. I’m not sure how 10 days of sudden unrelieved pain is considered by a rat, but it sounds acute to me.

Here we see in miniature the flaws of basic science and public health policy alike in their promulgation of questionable “evidence.”  A rat study headlined “Narcotic painkillers cause chronic pain” – that  doesn’t mention the rat subjects – is the latest example of the pendulum being pulled back so far it is straining credulity as well as contributing to people’s suffering.

The next time a patient of mine becomes a rat, has its sciatic nerve constricted with sutures, and asks for 5 days of morphine near its spinal cord 10 days later, maybe I’ll take another look at this study. In the meantime, I’ll tell my patients to ignore the unbalanced news coverage that the research spawned. I’ll also follow universal precautions in prescribing opioids, listen carefully to my patients and their context, work to find the best approach for mitigating their pain, limit side effects and untoward outcomes, respond effectively should they occur, and practice with a compassion not shown to these rats.

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Comments (23)

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Lynn McClelland

June 2, 2016 at 1:13 pm

I’m not sure why this particular study is being treated like it’s something new, though, opioid induced hyperalgesia is has been known in the literature for a while–there’s a pretty strong argument that opioid drugs do make chronic pain worse and longer lasting in some patients. See, e.g., Lee, et al., A Comprehensive Review of Opioid-Induced Hyperalgesia, Pain Physician 2011; 14:145-161 or Angst and Clark, Opioid-Induced Hyperalgesia: A Qualitative Systematic Review, Anesthesiology 2006; 104:570–87

    David J Olshefski

    June 3, 2016 at 12:36 pm

    I am sure that in some Patients Hyperalgesia does exists ,and there are some People that abuse Opioid’s,but certainly it is not good Ethical Practice by the CDC to spread to the Media these Non Human studies and cause a Frenzy in the Treatment of Chronic Pain . Giving a wake up call to Doctors to PRACTICE Common Sense (which many have gotten away from) when a Patient has Chronic Pain and needs Relief.Please Understand that we live in USA and there is American Disability Act that Protects Peoples Rights to to Recieve treatment and get it in a timely manner ! Lawyers will be having a Frenzy on this and i am sure a Supreme Court Case in the near future !!!

Fred Kaeser

June 3, 2016 at 11:10 am

We can all “Hail” opioids for their benefits…and yes, while opioids have provided pain relief since ancient times, let’s not forget that they have also contributed to dependence, addiction, and death since ancient times. And the latest research pegs the addiction and misuse rates for chronic pain patients at 10% and 25% respectively (http://newswise.com/articles/rate-of-opioid-misuse-is-around-25-percent-addiction-rate-10-percent-reports-study-in-pain).
Let’s keep our discussions about opioid medications balanced and objective…that is, opioids can provide great benefits AND they can provide great risks.

    Holly Davidson

    June 3, 2016 at 12:56 pm

    Thank you very much Dr. Martin! As a chronic pain patient all I want to say is we all need more Doctors like you!

    Lauri Nickel

    June 3, 2016 at 9:02 pm

    In reply to Fred Kaeser’s statement, the addiction rate for compliant chronic pain patients is VERY low, under 3%. According to this study, it’s under 1%: http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2007.00370.x/full

    Jeanine Ruble

    June 3, 2016 at 9:45 pm

    Oh yes, they can be harmful to addicts and I’m pretty sure that everyone knows that. Your comment, “Lets not forget them.” The problem is, We pain patients that require pain relief are forgotten. It’s not balanced. We are thrown in with the drug abusers and forgotten about!

      Ruth Dugger

      June 4, 2016 at 7:00 pm

      I agree! People who abuse them for a high make it difficult for the ones who truly need them for chronic pain.

Judith Bruno

June 3, 2016 at 2:02 pm

Please start asking some real questions like are any drug addicts no longer abusing drugs with these policies because we know that Prohibition does not work? The country is so concerned over the raise in heroin addiction and you will find, if you really look, that the raise is directly connected to these policies because if a drug addict can’t get the pills they want, they will and are turning to heroin and now our government is supporting the Drug Cartels who will get a drug addict anything they want just as the “Mob’s” did for alcohol. Did we learn nothing from history?

Why is the life of a drug addict more important than the lives of those who are in pain? Why are politicians acting as doctors in the decisions of what is the best way to treat us?

Mothers can no longer care for their children and bread winners no longer able to support their families. Who is going to pay for that care and where will that money come from? Who is going to care for those like myself who strive to stay independent and live within the boundaries of our disabilities but can no longer do so without the pain relief we need?

Health Care in this country is going to fail under these policies and it must when doctors refuse to take on patients who are in pain, clinic are closing and good doctors can no longer treat their patients in the way they know is best without fear of prosecution? Who are they going to blame for this? Obama Care? Someone must be blamed for the failure of our health care system to deal with those who are in pain.

Chronic Pain is a disability and we are being discriminated against because of those who will and do abuse drugs just like any religion or race who is discriminated against because of the actions of a few. We need someone to stand for us, talk about us, do something for us in this losing war on drugs.

We are told that 13% of Veteran’s abuse drugs but what about the 87% who need relief from pain and now can’t get that relief? Chronic Pain can and does kill and those who can no longer deal with a life in pain 24/7 will take their own lives and Veterans are the most vulnerable after the horrors of war. America makes these Veterans and makes the pain they now live with and yet we are turning our backs on them and telling them there is nothing we can do for the pain they are in.

Why aren’t pain patients given the same rights as others to decide what is the best care for their problems? Politics needs to stay out of our relationship between our doctors and the care we need.

Please do your jobs, do it right, look into the problems these policies are making that no one will talk about because of the fear of supporting drug addicts but we are NOT drug addicts, we are patients who need help.

Please look into the politics of all of this as we know the reasons behind this attack on pain medications after losing the war on Marijuana, which will become legal in this country, in order to validate their existence and the billions of dollars wasted in this losing war on drugs are now attacking those who are in pain. Look into the big pharmacies and the fight against them and yes, they need to be held responsible for never finding cures but only drugs that mask the symptoms to make more money but taking all of this out on those who’s only sin is that they are in pain, is not the right way to fight any of these injustices.

Please, think of the quality of life of those who are suffering in pain and think of your families, your parents, your children and how you would feel if they were suffering in pain and told there is nothing that can be done.

Help us, help the millions of American’s both Veterans and civilians alike who are actually being tortured because of these policies. Please look at all sides of this war on drugs and the dangers of drug abuse but remember, there are millions of us who need relief from our pain. They can’t fix the problems, can’t give us what we need to live with any kind of quality of life without the pain medications that are available so why are they torturing us?

    Ann Bradford

    June 3, 2016 at 6:17 pm

    What we need are more courageous doctors to stand up and speak for the chronic pain patient, not just the addict.thank you for your efforts to do so. I am a patient, not an addict.

    Jeanine Ruble

    June 3, 2016 at 9:41 pm

    Very well said Judith!

Morgan Thorne

June 3, 2016 at 5:52 pm

Thank you for your thoughts. I’m one of those people that opioids have helped immensely – I would be dead without them.

My previous doctor decided that because I still had significant pain from CRPS, even with “extremely high” doses of hydromorphone (12mg extended release 2x day), that I had opioid induced hyperalgesia. The truth of the matter is that the hydromorph wasn’t the best medication for me, but even still, I was able to function and care for myself. She thought I should be able to return to work as a paramedic, since I was on medication. So when I tried to tell her that it wasn’t possible – I now walk with a cane and have CRPS in my right arm and both legs – she decided it was time to wean me off and try all the medications I had already tried twice (believe me, I tried everything before resorting to opioids. I worked with addicts previously and the meds terrified me).

Within 6 months I was bed-ridden, planning suicide. I couldn’t walk, I couldn’t prepare food, I would go weeks without a shower because I couldn’t make it to my shower chair. My quality of life was non-existent.

I got a new doctor and a prominent pain specialist suggested fentanyl. At a relatively low dose, I’m functional – when I was able to walk again, I took trip to Mexico and climbed pyramids! My pain is still significant, I still need my cane, but I have a life again. I don’t wake up each day wishing for death. I don’t cry all day.

I share my story as widely as possible, to show what happens when chronic pain patients are denied opioids.

I’m also curious, did the researchers interpret the rats moving their affected limb away from the pain stimulus as increased pain? I know that when I’m without my pain meds, two things happen. 1) I don’t notice ‘minor’ pain, like a broken finger, because my brain is way too busy dealing with the serious pain of CRPS (gateway theory). 2) Even if something is painful, it often hurts too much to move, which means that I won’t always move away from something that hurts – it’s a case of deciding what will hurt more. I wonder if the rats were affected the same way?

Colleen Zinck

June 3, 2016 at 8:30 pm

What I think is going to happen is real Chronic pain patients are going to end up slightly abusing their pain meds because with all of this going on, they are now being under treated for their pain. I’ve been in severe pain for several years and my dosage has been decreased. While I believe having your dosage decreased every once in a while and then increased, it creates less dependency. I’ve even done it myself and skipped a few days or took half my dosage then went back to the regular dose and it works better for a while. No one thinks outside the box or has any common sense. And don’t they know that people with chronic pain don’t get high or this euphoric feeling. We get pain relief. It works like it should for us, it takes the pain away. Drug addicts have no pain so the drug works differently. This entire topic reminds me of the gun control issue. Oh some wacko went out and killed people so let’s take all the guns away. Oh musicians and drug addicts are overdosing and dying so let’s take all the meds away from everyone, even the people who need them for quality of life. Unless you’ve experienced chronic pain, you won’t get it!! I’ve been bed ridden for almost two years as the pain meds just take the edge off. I’ve parented from bed. I had cancer, was treated with high doses of chemo and then was finally diagnosed with SEVERE Fibromyalgia. Constant every day pain and fatigue. No quality of life. By not properly treating people in pain appalling. Doctors don’t half treat people with depression and anxiety. Oh here is half the dose of depression medicine for you. Learn to live with it! It’s not our fault nor really our problem that other people are abusing the same medicine I need to have at least some quality of life!! Chronic pain patients now are not getting the proper treatment, dosage and compassion that we deserve. Some Chronic pain patients are not even treated at all with ant type of pain meds. Make medical marijuana legal in all 50 states. They have that down to a science now and what exact strain you need for specific pain issues. There’s no cure for Fibromyalgia and the other approved drugs for it don’t work! If there’s no cure, then treat the symptoms! PAIN!

Lauri Nickel

June 3, 2016 at 8:50 pm

I found the rat study horrific but oddly, it actually proved a point — that anything, anything at all, when introduced intrathecally, puts a patient (a human one, anyway) at a huge risk for adhesive arachnoiditis, one of the most painful conditions in the world, ranking just under RSD/CRPS on the McGill Pain Scale. Failed pain relief in the rats was very likely due to the puncture of the dura, which then actually INCREASED the pain in the rats by inflaming the arachnoid layer of the meninges. What an ignorant, mis-managed, skewed “study”! I got arachnoiditis from a epidural steroid injection — don’t make the mistake I did!

Brooke Taylor

June 4, 2016 at 2:33 pm

Thank you for defending chronic pain patients. I have “lived” with chronic pain for 13 years. I’m only 35 years old. I can’t imagine living the rest of my life in this much pain. The CDC guidelines have made it even more difficult for chronic pain patients to obtain medications that enable them to live a quality life. Patients are being cut off of their medications completely or their dosages have been drastically decreased, causing needless suffering. Research shows that untreated or under treated pain negatively affects the cardiovascular, immune, neurologic, and endocrine systems. Not to mention the psychological disorders..depression, anxiety, and insomnia. I live in constant fear that my medication will be reduced or that I’ll be taken off my medication completely. I already live a life on house arrest. 95% of the time leaving the house only for doctor appointments, tests, or procedures. My crime? Having diseases that cause severe chronic pain. The media only tells one side of the story…and most of what is reported is untrue or important information is left out. This impacts the millions of Americans suffering from chronic pain. The media doesn’t want to report the truth about chronic pain patients or how the CDC guidelines are affecting us. The media fails to report research about chronic pain. Research indicates that a low percentage of chronic pain patients become addicted to pain medications (8-12%). It’s 2016, we live in a world, where we have access to medications that can ease debilitating pain..enough so chronic pain patients can have a resemblance of a life. Chronic pain patients are committing suicide since the CDC guidelines and the DEA crackdown. (There are many reports of suicides..I’m sure there are many more that were said to be “accidental overdoses”.) The media needs to start reporting the WHOLE truth…not leaving out important details of research studies. The media also needs to report the truth about chronic pain patients, the struggles we face, the stigma, and how the CDC guidelines are negatively impacting our lives. The chronic pain community is screaming out for help..no one is listening. How many lives will have to be lost before we’re heard?

Richard A. Lawhern

June 4, 2016 at 3:41 pm

As a non-physician patient advocate, author, and webmaster for peer-to-peer chronic pain communities, I have talked with thousands of patients during the past 20 years. Of those, a minority were prescribed opioid medication, generally in combination with other drugs (notably anti-seizure and tri-cyclic antidepressants used off-label for pain). Opioids are almost always a last-resort alternative after multiple therapies have been attempted and failed.
In all of this time, I have heard of a few patients who built so much tolerance to an opioid that they had to be tapered off from very high doses and then tapered up on different meds. One or two were forced to enter narcotic detox. But I have never encountered a clear indication of hyperalgesia confirmed by a medical doctor.
I have also heard from literally hundreds of people who have successfully used opioids for five to ten years or more at stable doses. In many cases, opioids are the only therapy that gives them even marginal quality of life. However these people are invisible in the medical literature; their long term experience has never been studied, and was not reflected in the proceedings of the CDC Consultants’ Group that drafted the recent changes to medical guidelines for the prescription of opioids for adult non-cancer chronic pain patients.
In the support work I do with chronic pain patients, I almost daily hear from one or more people who are being forced to taper off opioids by doctors who are suddenly gun-shy of DEA prosecution if they continue prescribing at doses above 50 MMED (Morphine Milligram Equivalents per Day — itself a highly problematic if not mythological unit of comparison). In some cases, patients have been summarily discharged by pain management specialists, without referral for either pain management or withdrawal management from their meds. I know of at least one death from side effects of withdrawal, and I have seen indications of more coming in a potential wave of suicides or street drug overdoses in people who have been plunged into despair and can no longer find effective pain relief from medical providers.
The CDC voluntary guidelines are neither voluntary nor guidelines. They are becoming a defacto mandatory restrictive treatment standard due to fears of DEA prosecution. And they are directly responsible for plunging thousands of patients into agony. The CDC needs to be bludgeoned into retracting these guidelines for major re-writing by a new consultants’ group — this one to include multiple Board Certified pain management physicians who actually and routinely see patients (unlike the group that produced the present one-size-fits all nonsense).
Failing the voluntary withdrawal of the CDC guidelines, it may be necessary to file a class action lawsuit against the people who served on its consultants group, and their overseers on permanent staff with CDC. Grounds can include medical negligence, denial of care, and possibly facilitating desertion of patients in desperate need of pain relief.

Kathy Campbell

June 5, 2016 at 8:07 am

If you have a well documented disease or conditions that are known medically to cause pain then how can the medication be causing it?

Michelle L Jimerson-Mo

June 5, 2016 at 1:56 pm

I also am one of the chronic pain patients that is being helped by opiods. My neuralgias are all in my head and even though I usually only take one opiod a day it has given me a life where I can take care of my children, my house, work again as a research historian at home and help at our other home businesses. Most of our drs, neurologists and pain specialists have stopped prescribing narcotics. I’m on preventatives too, but the triggers are still there. I can’t take triptans, so opiods are my only abortive option. I’m not the only one. So many on the peer boards take opiods boards. Many take more than me, but there is the fear that our drs won’t continue with our prescriptions. Thank you for this article. Please continue spreading this information countering the hysteria that’s out there. We are not the problem, yet we are lumped in with the drug seekers and many times unable to even go to ERS when our home meds don’t work. Just to end on a positive note, my neurologist does not have a problem writing me my scripts, she takes the whole person and conditions in account like you do Dr Martin, but are you all becoming rare in your treatment of the person? I hope it isn’t true and the pendulum against the fear of harmful mess of opiods changes.

Paul Scott

June 6, 2016 at 8:21 am

Late to this very bizarre piece. Strange to see it in HNR and by a member of NPA which should be attuned to the pivotal place of industry misrepresentation in the opioid epidemic. The study was indeed a rat study, and the articles I read said as much. OIH is intuitively sound however (what is tolerance and withdrawal of not a worsening of the initial symptom) and a syndrome supported in many lines of evidence if not RCT. Clinically, the Mayo Pain Rehab program reported that the more opioids a patient was on the worse the pain, and weaning reduced pain, but never mind, because this piece is busy condemning CDC guidelines and the rest. Amazing, RIP Prince.

    Katie Hill

    June 6, 2016 at 9:44 am

    Thank you for being a voice of rationality. It is illuminating to read a description of this study, and alarming to see how the media has distorted it. As a chronic pain patient, I deeply appreciate having an educated and knowledgeable medical voice speaking in the media as a balance to the recent overreaction of the CDC. I’m also glad I’m not one of the rats which were tortured in this ridiculous “study.”

      Paul Scott

      June 6, 2016 at 10:48 am

      To clarify, because a reply to my comment suggests otherwise, I am in total disagreement with the author of this commentary, believe hyperalgesia to be credible and think the CDC guidelines are a brave first step in ending or severely limiting the use of opioids for non cancer chronic pain.

David Spero RN

June 6, 2016 at 11:40 am

Not only drawing completely unsupported conclusions, but torturing animals to do it, for no apparent reason other than publicity seeking.

    John Holmes

    June 8, 2016 at 4:26 pm

    This is an interesting blog: Dr Martin essentially concludes that He essentially concludes that “because the implications of the study were blown out of proportion by the media, I’m going to ignore this study, stick my head in the sand and keep doing what I’m doing”
    That strikes me as problematic, as the long-term effects of opioids (good or bad) have not been systematically studied. Surely that work needs to be done before dismissing new research?

Christopher Grammar

June 8, 2016 at 3:42 pm

165,000 deaths from prescription opioid use. 2007 Felony conviction of Purdue pharma for false promotion. Multiple lawsuits-read City of Chicago vs Purdue Pharma et. al. Pain the fifth vital sign another Purdue promotion. No landmark study no scientific breakthrough. I remember Nora coming to my pain clinic and offering me 2500 dollars all expenses to go to Florida and become a KOI Key opinion leader. Lynn Webster who invented the opioid risk tool whose pain clinic had so many deaths the Feds investigated. Insys who marketed opiates for non acute pain using strippers. It goes on and on. Reasonable opioid prescription? Like reasonable shop lifting. Give it up. The nails are slowly being driven into the coffin. Opiates are insecticides make by the opium poppy to kill a bug that eats its leaves. Endorphins are part of a rich choreography between pain and stress. Give exogenous opiates and the brain makes less endorphins. Take out the violin put in a tuba and play the symphony. See what happens. OIH is real and occurs in all patients prescribed opiates to a varying degree. It occurs in healthy volunteers and has been documented since 2006.