The Neuromythology of Persistent Pain: OOPS I Did It Again

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Perhaps because I’m a pharmacist, I am unable to see people’s receptors with my naked eyes. Notwithstanding, I continue to see and hear from some pain colleagues who, it seems, can see them. These folks have a formidable talent that enables them to detect clinical phenomena habitually – an “attribute” that I think I have seen only a handful of times – opioid induced hyperalgesia, it’s cousin, central sensitization, and now opioid overuse pain syndrome or OOPS, an acronym coined in Mehendale et al recent publication [1], that will foster more indignity to patients with chronic pain. In fact, an entire neuromythology[2] has developed – not that these phenomena do not exist; but that people believe they can diagnosis them clinically.

Equally disheartening is the commensurate Oops “Letter to the Editor” by Manchikanti and colleagues.[3] This appeared three days after my initial draft of this blog, which just confirms what I am about to say below. His group goes on to criticize Dr. Russell Portenoy and supports this with what we all know not to be a peer reviewed medical resource, The Wall Street Journal – an earlier blog here nicely castigates that gem of an article.

Let me explain what I think constitutes our phenomenology: when patients come to see us, they are often hurting physically and emotionally. They are, after all, seeking consultation with an expert, perhaps because they have not responded to earlier efforts at the treatment of their pain. They are hurting, stuck, doing poorly, suffering and/or desperate, downtrodden, hopeless and even suicidal. Some perhaps have done well previously on a regimen of medication, interventions, non-medical therapies, diet and exercise, but now they have taken a turn for the worse and nothing seems helpful, including their medications at higher doses. Many are the salt of the earth – hardworking folks injured on the job or elsewhere. Many of them have been suffering for years. No one thought they were malingerers when they were operated upon for the 5th time. No one thought they were lazy good-for- nothings when they had their 3rd or 4th or 5th procedure. But the perception of them seems to change when their opioid regimen is stalling and running out of gas.

Many of us see daily “stuckness” and waning efficacy of treatments that might have seemed promising at initially – this of course is frequently seen several times in a single typical clinic day. We pain clinicians are often in this “stuck” business. Our patients are stuck in terms of pain or function or both. We have been put on this earth to unstuck them. To help them find hope and courage and face their pain, alter or change completely their life plans to accommodate to it, to find the creativity it takes to distract oneself, cope, or simply bear a painful existence.

  • Some of these people will undoubtedly be improved off of opioids. Does this prove they were hyperalgesic on a cellular level?
  • Some will be better with a dose increase. Does this prove they were tolerant on a cellular level?
  • Some will be better with psychiatric treatments. Does this prove it was all in their head or they were serotonin deficient?

To insist that treatment proves a cellular level diagnosis is to invent a neuromythology. Now these terms are decidedly nicer than malingerer or good-for-nothing. And while less mean-spirited they are no less damaging in some respects. Not because they aren’t potentially relevant concepts in clinical decision making, but because they are often applied inflexibly and are used as a substitute for clinical decision making.

I have previously written in this blog about how our healthcare system can’t handle the opioid risk mitigation tools or the education, time, and effort necessary to allay the peril of our patients – at least not without massive changes. What our system can do with less of, is practitioners mistakenly thinking they have X-ray vision but are blind to the suffering of the people who come to see them. And unfortunately, the influence of such opaque teachings as seen in Mehendale et al [1] “is problematic because it wastes money, time, and effort, which could be better spent on the development of evidence-based practices.”[2]

Perhaps we can remind ourselves why we are in existence and how desperate patients might perceive us, by extracting certain of the lyrics from Brittany Spears’ rendition of Oops, I did it Again.

Oops!…I did it again to your heart
Got lost in this game, oh baby
Oops!…You think that I’m sent from above
I’m not that innocent


  1. Mehendale AW, Goldman MP, Mehendale RP. Opioid overuse pain syndrome (OOPS): the story of opioids, prometheus unbound. J Opioid Manag. 2013; 9(6): 421-438.
  2. Dekker S, Lee NC, Howard-Jones P, Jolles J. Neuromyths in education: Prevalence and predictors of misconceptions among teachers. Front. Psychol. 2012 Oct 18;3:429.
  3. Manchikanti L, Atluri S, Boswell MV, Hansen HC. Letter to the Editor. Opioid overuse pain syndrome (OOPS): the story of opioids, prometheus unbound. J Opioid Manag. 2013; 10(2): 81.

11 thoughts on “The Neuromythology of Persistent Pain: OOPS I Did It Again

  1. Awesome piece…were i religious this would be a place i’d say “God bless you”. You get the idea.

    Other thing i love about the elusive-to-you x-ray vision is  the extent to which such subjective criteria are affected by  patient gender, age, culture, etc. Many years ago a close friend (and pain patient who subsequently suicided due to intractable pain and intractable pain specialists) told me she was treated differently if she showed docs photos of her with her grandchildren, told me it helps if the doc settles on a respectable, relatable version of the patient.  I don’t see any doctors anymore without a member of my family present: i’ve tried it both ways for years, and the results were statistically significant to the tiniest p value…

    Thanks again for all you do.

  2. I have been suffering with chronic pain for 25 years now. OxyContin was the first medication that finally got my severe chronic cervical pain under control after suffering for 10 years. After about 6 months on a certain dose I needed a increase in dosage to achieve the same pain relief. After 5 years on OxyContin I was at a high dose and I was beginning to get concerned about these increases. I was on Purdue patient assistance program. Medicare part D was coming out and they told me your Purdue assistance program will end when you choose what part D program you sign up with. My doctor took me off the OxyContin and I was placed on Methadone. I had no side effects ,no withdrawals everyone said I would have just the pain relief I needed. And till this day am on the same dose of methadone. So everything seemed to fall in to place, I’ve been blessed to have had such caring doctors. Everyone worries about these ridiculous stories that some doctors make up about opioids that are just not true . Some may have half truths to them and then the rest is blown out of proportion.
    Everyone needs to stop worrying and go about your life with a lot less stress as it causes more chronic pain and hypertension you don’t need. All this stress can kill a person and I’m not going to be one of them. I see this in my parents and a lot and doctors along with chronic pain sufferers worrying about every little thing ,blowing things out of proportion when it needs to be left as is.
    This thing about opioids and chronic pain has been blown so far out of proportion its ridiculous to the point of insanity. We need to get back to the things that really matter, the future of Pain Management.
    All this heckling about opioid-induced hyperalgesia may be true for some but before detoxifying patients from opioids I would first try opioid rotation, then proceed from there.

  3. It almost seems as if these pain specialists created a syndrome out of thin air just so they could get credit for “coining” a phrase.

    Nice try, but I don’t think “OOPS” will stick.

    Next time please use an acronym that is more dignified and less harmful to the precarious psyche of chronic pain sufferers.

    “OOPS” sounds juvenile.

    Thank you, Dr. Fudin for your courageous article. It hits the mark.

    – JPM

    1. Thank you Dr. Murphy for always treating your patients as just that, “patients”. I am honored to call you my doctor. One day you said, “I love my job. I truly enjoy making people feel better,” I could see in your eyes that you meant it. You are a jewel amongst a bunch or rather tarnished and bitter physicians. I can’t say I can even blame them all that much. It’s been no fun for anyone, this war on pain patients, but you have stayed steadfast to you Hippocratic Oath and tried to remain a REAL caregiver.

      Stay true to yourself, Dr. Murphy, it’s served you well.

      Kimberly Miller,
      U.S. Pain Ambassador

  4. Thank you Dr. fudin (& Stewart!).

    The “phenomenon” referred to as Opioid Induced Hyperalgesia, and now “OOPS” is becoming just another overused, over diagnosed, theory that has the potential to ruin lives. It is more medical jargon being used (and abused) to deny and / or discontinue opioid therapy to patients who need it.

    From my understanding, OIH has been studied in rodents using heat related pain. I have also read that OIH is thought to develop in less than 5% of patients. How this translates to an entire population of patients on longterm opioid therapy is beyond me. I have also heard doctors talk about their “observational studies” of hospitaized inpatients on opioids who seem overly sensitive to pain. What they DON’T say, is that many of these “overly pain sensitive” patients have just undergone extremely painful surgeries, and are having a hard time obtaining their usual daily doses of prescribed opioids, LET ALONE any additional medications that would be required to address the NEW, ACUTE post-surgical pain.

    Another issue I have with these overused buzz words is this: Why is it, that with every OTHER treatment for pain… Procedural, medicinal and CAM therapies, patients are told not to expect miracles, to realize and expect that they WILL continue to have some pain. That there is really nothing that will relieve ALL their pain….. BUT, if they’re given OPIOIDS, they had better be pain FREE!! If their complaints of pain continue (even in the face of disease progression or acute injury), they will blame the opioids for CAUSING it? The cure becomes the cause…. I don’t think so. Certainly not in any statistically significant way that can be translated onto a group of patients who have found serious and meaningful relief from daily debilitating pain.

    About four years ago, prior to finally being properly diagnosed with Ehlers-danlos Syndrome by a Boston geneticist, I had my one and only appointment with a Pain Management physician. It was at the esteemed Massachusetts General Hospital. I saw a doctor who didn’t examine me, had only a brief medical history, and spent about ten minutes talking with me. (he didnt make eye contact & mostly spoke to my husband….you know…. MAN to MAN). After our brief meeting, he sent letters to three providers who I had seen over the last year or so. In these letters, he advised them not to give me any opioids for my severe pain. Why? Because I would develop Opioid Induced Hyperalgesia if they did. Thankfully, those providers who received the letters recommended that I not go back to him again. I didn’t. What I did do, was have my pain aggressively and adequately treated with opioids. It saved my life….

  5. @Stewart: As a friend (and now co-author) of Jeff’s, I have to disagree with you regarding OIH. Please refer to the following study, which provides at least a modicum of support for the concept:

    J Opioid Manag. 2006 Sep-Oct;2(5):277-82.
    Significant pain reduction in chronic pain patients after detoxification from high-dose opioids.
    Baron MJ1, McDonald PW.
    Author information
    Opioid tolerance is a well-established phenomenon that often occurs in patients taking opioids for the treatment of chronic pain. Typically, doctors need to periodically elevate patients’ opioid doses in an attempt to manage their underlying pain conditions, resulting in escalating opioid levels with only moderate to negligible improvement in pain relief. Recently, opioid-induced hyperalgesia has been recognized as a potential form of central sensitization in which a patient’s pain level increases in parallel with elevation of his or her opioid dose. Here, we report a retrospective study of patients undergoing detoxification from high-dose opioids prescribed to treat an underlying chronic pain condition which had not resolved in the year prior. All patients were converted to ibuprofen to manage pain, with a subgroup treated with buprenorphine during detoxification. Self-reports for pain scores were taken at first evaluation, follow-up visits, and termination. Twenty-one of 23 patients reported a significant decrease in pain after detoxification, suggesting that high-dose opioids may contribute to pain sensitization via opioid-induced hyperalgesia, decreasing patient pain threshold and potentially masking resolution of the preexisting pain condition.

    Additionally, 27 years in clinical practice detoxifying patients from opioids (perhaps 500 patients in total) with only ONE not reporting significantly decreased pain following detoxification provides relatively strong anecdotal evidence.

    Irrespective, I continue to posit that there is a select subpopulation of patients with chronic pain that can do well with chronic opioid therapy. Additionally, based on the principle of respect for patient autonomy, is it not the provider/patient dyad that should be making choices about whether to pursue COI – particularly when no other treatment options are available? Please look for a lengthy editorial that I wrote with Jeff and Tim Atkinson that will be coming out in my journal, the Journal of Pain Research, in 3 weeks or so. Let’s not be extreme by referring to the zealots as “twisted”; rather, they’re merely “unrealistic” – and typically in academic pain centers where they enjoy an embarrassment of referral options for their patients with chronic pain. It would be nice if they sunk down into the “real world” for a moment or two.

    1. Michael,

      I look forward to reading your upcoming lengthy editorial in your Journal of Pain Reseach. As of now, I’m a bit confused about the fact that you’ve helped 500 (or so) patients detox from opioids, and only ONE of them didn’t report a significant decrease in pain…. I’m wondering if you could be a little more specific about who those patients were…

      We’re they patients who had been taking them continuously despite having had their pain resolve? Were they addicts who obtained them illegally, and developed OIH as a result of taking opioids when they didn’t have pain? Were they perhaps inappropriately prescribed opioids in the first place? Were they addicts seeking to get off of them because they finally realized their lives were in danger?

      With all due respect, I can tell you with absolute certainty, that if you took someone like me off opioids, I would have to go to the ER every time a joint dislocated (maybe five times a week, and sometimes daily), I would have to stop volunteering in my children’s classrooms, I would get a divorce, I would stop having sex, I would stop eating, I wouldn’t attend any activities for my kids (school functions, sports events, plays etc…), I would need assistance bathing, washing my hair, and dressing, I would stop doing the things around the house that I am STILL able to do, like laundry, light housework, etc…. I would acquire massive debt, like I did prior to starting opioids, because of the thousands of dollars I paid for accupuncture, massage, meditation classes, repeated procedures & doctors appointments, months of PT @ $20.00 out of pocket costs, three days a week, babysitters (for help during the day, because I couldn’t sleep at night), the EIGHT large tubs ( from AMAZON) of TigerBalm that I bought & went through every three weeks!!! I would also lose friends, relationships, autonomy, self-esteem, sanity, and above ALL… My will to LIVE.

      I don’t say these things lightly. So for the patients like me, who benefit, and are able to really HAVE a life because of opioids…. It is unfair to make such vague statements about what happens when people are taken off opioids…. And the 99% rate at which patients developed OIH. It is misleading for you not to be more specific about those 499 people out if 500 who had OOPS, OIH, BS, or whatever else it’s being called. Could you elaborate?

      Thank you!


  6. Here we go again with something new a doctor thinks he knows the answer to after all these years . (OOPS) opioid overuse pain syndrome , this would apply to those who abuse opioids for all the wrong reasons. Also their excuse for wanting more opioids for their habit that they feel as chronic pain, when indeed is a addiction disorder to opioids. People with pain of a psychiatric disorder think using opioids will cure their pain problem. These people with mental disorders need help from the proper specialist and the correct medications.
    This will continue and be yet another hurdle for those who truly suffer from never ending chronic pain .

  7. Another excellent post, Jeff. I don’t recall ever seeing a randomized, controlled trial demonstrating the existence of OOPS — or, what used to be called OIH (opioid-induced hyperalgesia) — in a population of patients with chronic pain. In fact, I don’t believe there’s even been an observational, cohort study of this alleged phenomenon. While there has been reasonable suspicion of OIH in animals and small samples of opioid-addicted persons to build a theoretical framework, the reality of OIH, or OOPS, seems to exist mainly in the twisted minds of pundits who use it as one more reason for denying legitimate patients in need of their opioid medications. But, that’s just my perception — I unfortunately have no clinical evidence to prove that those “experts” are truly warped.

    1. A heartfelt thanks, once again, to Dr Fudin and the rest of you for continuing to carry the fight for legitimate science to the ***s at PROP. I just cannot come up with a polite word instead of *** to describe those people who are deploying every known stunt of semantic trickery and fake logic to force me (and who know how many others?) back into the haze of unrelenting pain and gabapentin-induced stupor that preceded my prescription for extended-release morphine.

      Even the few PROP-sters who seem to agree that my case is legitimate throw into my face the 16,000 annual deaths arising from the misuse and abuse of opioids, with no further explanation of how my action leads inevitably to the other. It just does, dammit!!! Everybody with half a brain knows that correlation equals causation!!!

      Also, a salute to Danya Zucker for reminding pain sufferers to take a family member along to every medical appointment. I would only add that the family member should be along to every initial appointment, even if your immediate complaint has nothing to do with your chronic pain.

      I sure hope and trust that science will eventually prevail over politics, as Nate Silver kind of predicts in The Signal and the Noise, pages 410-11.

    2. Here’s my own anecdote to expand on Dr Leavitt’s thoughts on OIH.

      My pain consultant, a really humane, smart, sympathetic human being, greeted my wife and me about 4 years ago with more enthusiasm than usual. I suspected that he had come up with a new treatment that he was going to tell us about later.

      But when he cleared his throat and announced that had some new information for us, he said we needed to know about hyperalgesia — an event where increases in opioid pain reliever doses paradoxically increase the pain when the opioid is taken for too long and in dangerously high doses. He pulled out a diagram of the nervous system and presented a 15-minute explanation of how hyperalgesia worked. Yikes. At the end, we said we kind of understood the concept, but not the probability that I would get it myself, given my personal history with morphine ER. Could he give us links to case histories so we could plot out the probabilities ourselves?

      His body language and verbal tone changed from their usual self-confidence, he shuffled his feet, stared at he floor and said that, unfortunately, there was little conclusive clinical evidence to examine, but we should understand that there was p[enty of evidence from experiments on laboratory animals on how real and alarming hyperalgesia was, so I should really think hard about whether to continue with opioid pain relievers. Unfortunately, he had no new ideas about non-opioid options or information about what constituted “high” doses of meds or how long was “too long” to be taking them. I’m still looking for clinical accounts to help me sort out whether i’m really at risk of OIH or not. Along the way, I did come across a statement by a group of researchers questioning whether OIH even exists as a clinical phenomenon in humans.

      I’m not a professional, so I can’t follow how Michael Schatman’s article proves that hyperalgesia is a threat to me or why I should trade the known pain relief I get from Morphine ER today to avoid an unknown probability that the same medicine will increase, rather than decrease, my pain in the future. I do agree with his assertion that a decision on whether or not I should continue with opioid therapy should be made by me and the pain specialist, not by politicians or regulators reacting to PROP’s scare tactics and faux science.

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