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Opioids and Chronic Pain—A Gap in Our Knowledge

September 25, 2014

Opioid prescriptions have increased three-fold over the past two decades, and we have seen how this skyrocketing availability of medications has helped create a new drug abusing population, some of whom suffer severe health consequences. More deaths now occur as a result of overdosing on prescription opioids than from all other drug overdoses combined, including heroin and cocaine. The opioid epidemic is tied closely to another epidemic in our country, that of chronic pain—although the ties are very complex.

Chronic pain now affects more than a third of Americans (see Infographic below). Although chronic pain patients themselves account for only a small percentage of those who are abusing opioid painkillers and dying from them, these pain sufferers may not even be obtaining significant benefit from the opioids used to treat their condition. In fact, growing evidence suggests that long-term treatment with opioids may induce hyperalgesia, an increase in pain sensitivity as a result of the chronic administration of opioid medications, at least in some patients.

See caption
Chronic pain is a major public health problem. It affects more than one-third of the U.S. and 20%-30% of the world's population.  Prevalence of persistent pain is expected to rise with the increase in diabetes, cardiovascular disorders, obesity, arthritis and cancer in the aging U.S. population. Opioids can produce significant side effects such as respiratory depression, mental clouding, nausea, constipation and physical dependence. Opioid prescribing has increased 300% in the last 20 years. Today, the number of people who die from prescription opioids exceeds the number from heroin and cocaine combined. See a larger version from NIH Prevention site.

This year, the Agency for Healthcare Research and Quality reviewed studies on the effectiveness and risks of long-term opioid treatment of chronic pain. The results are eye-opening: No randomized trials or comparative observational studies meeting the reviewers’ criteria were found that addressed opioids’ effectiveness for chronic pain or comparing their effectiveness to other treatments, making it impossible to know whether long-term treatment with opioids adequately addresses patients’ symptoms or improves their functioning or quality of life. At best there was weak evidence regarding optimal dosing strategies with these medications.

I have argued before that opioids are overused and overprescribed because of a lack of clear understanding of how to treat pain by doctors. (Pain management is barely covered in medical schools—a situation that NIDA has worked to help rectify through various initiatives including leading the creation of 11 Centers of Excellence in Pain Education, in partnership with the NIH Pain Consortium and other NIH Institutes.) If it is indeed the case that opioid overtreatment is not only contributing to addiction but also contributing to the chronic pain problem, then that makes all the more urgent the need to investigate new treatment approaches and perhaps even create new medications that operate on other signaling systems in the body.

On September 29-30, NIDA along with the NIH Pain Consortium, the NIH Office of Disease Prevention, and the National Institute of Neurological Disorders and Stroke is cosponsoring a Pathways to Prevention workshop to discuss what we know and don’t know about opioids in the management of chronic pain. Participants will discuss the effectiveness and potential risks of long-term opioid treatment for different patient populations, different pain management strategies and their outcomes, ways of limiting opioids’ risks, and our future research needs.

Get more information on the workshop, The Role of Opioids in the Treatment of Chronic Pain. You can also see my video on pain research at NIDA and the NIH Pain Consortium (below).

This page was last updated September 2014


chronic pain

I do not know what I would do without suboxone for my chronic pain. I know I would kill myself if it was taken away from me and I had to suffer the intense pain everyday. I have scoliosis and it caused spinal stenosis, ddd, a missing vertabra and numerous other problems. My ribs have wrapped around my right lung and I have rods and screws at L5 that pinch my sciatica and walking with a cane helps the pain but I had to stop using it because it only worsened the scoliosis.


A couple of facts to bear in mind:

The Cochrane Library have concluded that cases of "iatrogenic opioid addiction [during long-term opioid therapy], were rare." http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006605.pub2/pdf/st...

Minozzi et al (2012) conclude that "The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence."

Dunn et al (2010) identified 9940 patients who had received 3+ opioid prescriptions within 90 days between 1997 and 2005 and only report 6 cases of fatal opioid overdose. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000551/?report=classic

Chronic pain from Myofascial Pain Syndrome/Fibeomyalgia

I can say that the pain that I have experienced without OxyContin, cyclobenziprine and Xanax was definitely life ending. This pain was unbearable. When I would make that comment to one Dr. He would think you need a psyc evaluation. Depression is "real" issue. NOT the case. If you suffered, at a 10 pain "scale for long periods of time, it wares you down mentally. It's "torturous". Your brain tells you that it can't physically take anymore. If a person had a beloved pet and the Vet said nothing can be done to ease its pain due to whatever, they would say it is the "humane" way to put your pet down. If you are a human, you look as if you are a drug seeker. What kind of Dr. Would let their patient Suffer endlessly ? I've been through many. My current Dr. Saved my life! It was my last attempt to give a medical "professional" a chance to help me lessen my pain. He wasn't afraid to treat me and tell me that he will help me figure out what doses would help me want to be around for my husband and 3 young sons.... Oh, how I thank God for that man... No person deserves to suffer! About 15 yrs ago, I took out a neurology book out from my local library. I read a section, (difficult at times to understand) that said ,"people that suffer with chronic pain metabolize pain medication differently than others". This is the truest statement I have ever read! There hasn't ever been a day, even during my first dose that I ever felt high, drunken feeling, numb, euphoria NOTHING!!!! I only feel a lessen in severity. Ex. Bad headache and you take Excedrine. Headache lessens and if lucky goes away. That's the same way I feel. I implore Dr.s to look into a patient and realize we are human and it's In humane to make us suffer. If Dr. Doesn't treat us, many would have blood on their hands..(patients will commit suicide to end the" Real" physical pain.

this whole post bothers me a great deal

There are all kinds of problems with the blog post here and as a person with a family member treated for chronic pain it is really disturbing, since it's proposing studies but heavily implies the forgone conclusion that opioid prescription in chronic pain patients is leading to an Rx opioid abuse epidemic. I have enormous respect for you and NIDA so I must raise many objections to this oversimplified explanation:
1. The post assumes that legitimate pain treatment is the cause of the prescription drug abuse epidemic. A basic observation of the phenomenology of prescription opioid abuse can tell you this is not the case:
a) Rx chronic pain patients at legitimate pain clinics are by and large not becoming addicts;this has been the story for a long time from many research studies, similar to amphetamine prescriptions for ADHD. It's not surprising since chronic pain patients at legitimate clinics are subjected to extensive intrusive random drug tests and their use of every pill scrutinized and shamed on a constant basis. Since all of these drugs (this month including Vicodin) are schedule II, this means in most states a new in person visit is necessary for each and every printed refill, usually at least every 3 months. I.e., these patients are so closely monitored it would be very unusual for them to accidentally end up as addicts without the responsible Dr's knowledge.
b) abused Rx opioids are usually purchased through a series of middlemen who are drug dealers. These middlemen hire actors to pose as pain patients who then go to phony baloney pain clinics (often in Florida) obtain thousands of pills and sell them at very high profit, usually 20-30 times the prescribed retail price. For example, the street price of generic Vicodin is $5-10 a pill, whereas if you had a legitimate prescription the value of such a pill is optimistically $0.20. Likewise, a standard percocet goes for $10, and is worth $0.15. Chronic pain patients, who are usually unemployed, are not buying these pills in this manner. For the most part, they can't even afford Oxycontin, most of them are on medicaid disability, which in and of itself is a tragedy, and have to rely on older generic painkillers including methadone to avoid ending up in the infamous medicare donut hole.
c) The Rx opioid abusers are fairly easy to spot; there is no long case history of hundreds of doctor visits to chase down the elusive "cause", no cancer, failed multiple surgery syndrome, neurological syndrome, phantom pain, nerve injury, organ removal, or whatever that accounts for their pain. The complaints are vague and the phony doctors don't follow up and don't care and hand out the Rx's like candy. These Dr's and the entire supply chain are the problem -- you should not hold legitimate chronic pain patients hostage because of them any more than an ADHD child should be held hostage because there are crystal meth addicts running around shaking and baking sudafed. These populations have absolutely nothing to do with each other and should not be conflated.. Rx drug abusers are not prescribed drugs by legitimate doctors. The rise of this practice is only possible because of inadequate enforcement at the level of medical boards, state police, pharmacy boards, and resistance of drug manufacturers to adequately track distribution. And it is a problem the FDA and a few other agencies could by and large solve. The recent Walgreen's $80 million oxycodone settlement (surprise surprise, in Florida), makes it pretty obvious that supply-side enforcement is almost non-existent (some pharmacies were distributing 2 million pills per month for years and no one noticed -- or cared to notice) and is where the problem lies.
d) opioid drug abusers do not use the drugs in the same way that legitimate pain patients do, since they won't produce an adequate high to support addiction. Even a cursory discussion with those abusers reveals they crush, snort, and smoke the pills, often at very high doses. In contrast, good pain control is obtained by rtc slow dosing. And some of those drugs -- like buprenorphine -- the slowest of them all -- addiction is almost nonexistent;; in fact, its used to treat addiction.

2. The little info box is also very misleading, since it is using a very straw man approach and doesn't list any actual numbers in the misleading death statistic which I have seen now in a dozen NIDA and CDC posts as it is totally out of context. Yes, rx opioid use results (barely) in more deaths than heroin and cocaine. You don't mention that heroin and cocaine deaths are quite small (not really a significant cause of death, even in addicts) and the total number of users of cocaine and heroin (maybe 1.5 million) is trivial compared to the number of rx opioid users (maybe more than 50 million -- Vicodin is the #1 prescribed drug in the US -- by far); the death RATE among users means they are among the safest drugs. 40 US deaths per day due to Rx opioid abuse -- it's an epidemic. What a headline. 1315 Americans die per day due to smoking. 241 Americans die due to alcohol use. Where is the drug abuse epidemic? RX opioids or the supermarket drugs that produce 35 times as many deaths? The other issue I have of course is that the assumption here is that RX opioids are somehow much worse than the alternative pain medications. We don't really know exactly how many people die from NSAID use a year, but the side effects of chronic NSAID use -- heart attacks, bleeding ulcers, and strokes -- are far worse than opioids. One study of NSAID use in rheumatoid patients concluded that about 16,000 deaths occur due (44 americans per day if you will) to NSAID use per year, just in rheumatoid patients alone. This means that NSAIDs -- which are not even subject to abuse -- kill more RH patients alone than RX opioids kill in the entire US population even when including abusers. The inescapable conclusion is that pressuring pain patients to move to NSAIDs would result in far more deaths. We don't even need to consider acetaminophen, which is now the number one cause of acute liver failure. The basic story here is you can drum up problems caused by opioids, but the reality is that the alternative pain killers are much worse. Yes, we need new pain pills that are better than opioids. And in the last 5000 years, these have failed to materialize.

3. The idea that opioids are not effective pain killers is fairly absurd. The basic pharmacology of opioids and their analgesic effects being uniquely on both nociception and pain perception means they will remain the mainstay of moderate or severe pain treatment for many years. It is not surprising since we have been using them to treat pain for at least 5000 years. The evidence for hyperalgesia here is overstated as well. There are studies showing hyperalgesia -- it is not a universal phenomenon, and if it does happen it's not that hard to spot since it involves dramatic doses, dose escalation, and allodynia. Those papers often say, well, suspect it if you see no disease progression, but loss of drug effectiveness and allodynia. The post here implies that hyperalgesia undermines the whole theory of using opioids to treat pain. You are forgetting that severe chronic pain patients have very severe quality of life problems (like being able to stand up, work, and wanting to kill themselves) and the list of opioid side effects listed are fairly trivial compared to these -- even if rapid dose escalation and dependence happened, they would be better off, and it usually doesn't happen.

My basic problem here is that the solution to the problem is not to punish legitimate pain patients. Right now, they are the only ones being punished since legitimate pain clinics are on them like white on rice. The problem is being caused by loose regulation of phony pain clinics, and very poor supply-side control, right down to drug manufacturers unwilling to track inventories, distributors not paying attention to Dr's and pharmacies prescribing massive amounts of opioids, and unregulated illegitimate pain clinics.

I agree there is a problem and it is very highly worthy of study but it needs to be approached without a forgone conclusion -- and it needs to balance the scale in favor of helping chronic pain patients who far outnumber drug abusers and suffer a worse fate than drug addiction. Their quality of life is often abysmal and they can see no reason to keep on living. They suffer enough for their pain without being shamed by NIDA for a related problem they are not responsible for causing.

Another knowledge gap

The US DEA quota for commonly abused prescription opioids increased nearly nineteen fold between 1994 and 2013. Specifically, DEA allowed the manufacturing for sale of a total of 302,359,000 grams of fentanyl, hyrdocodone, hyromorphone, methadone, oxycodone, plus oxymorphone in 2013. The total manufacturing for sale of these drugs totaled 16,271,000 grams in 1994. Source: Federal Register.

Because 19-fold is so much greater than the 3-fold increase described above, this appears to be another knowledge gap.

I STRONGLY agree with everything

I STRONGLY agree with everything Stephan just said. People with chronic pain are not the problem here with the drug abuse epidemic. Personally, I won't get into details, but my body is basically filled with cysts and tumors and I have been in constant pain for three years of my life. I have also been on lortabs for those three years, and without it I wouldn't be able to move.

Hyperalgesia is real, yes, but for most people the benefits of opiates outweigh the potential risks. And, YES - we are being punished because others abuse the meds we take. Because of all of this rescheduling BS, I had to spend my entire day (literally) trying to get my medicine that was due four days ago. The new laws that are supposed to be preventing abuse are just preventing ACTUAL PATIENTS from getting any sort of relief.

I agree with Stephen and Emily

I'm a chronic pain patient for over 3 years. Without medicines, I wouldn't be able to stand and walk, much less work or do anything fun. With treatment (including daily Norco use) I can live an almost normal life. I work, I pay taxes, I volunteer in the community, I teach Sunday School, and I could go on... It's true enough there are some doors now closed to me (running marathons, climbing mt everest, etc.) but thanks to a doctor who isn't afraid to treat chronic pain I have a pretty decent quality of life. There's probably some physical dependence on the drug at this point, but that's not the same as addiction. I can honestly say that if I woke up tomorrow and the pain was gone, I'd stop the meds all together. I don't think that's very likely, but I can still dream (which by itself is a testament to the quality of care I've had - many in my situation lose the will to live).

What to do in the meantime

I agree that there's a knowledge gap. I get the impression that our anti-drug culture predisposes people to jump on any possibility that pain drugs are overused. The key point is: what are people such as my wife with severe chronic pain supposed to do while waiting for alternatives? The reality is that currently drugs such as Oxycontin are what's available. In her case I have seen no evidence of addiction or over use. Also nay-sayers fail to mention that the formulation of prescribed Oxycontin has changed and is now in the form of a plastic like pill that cannot be crushed, making it very difficult to misuse the drug by bypassing its time release properties.

A key problem is that those without severe chronic pain do not understand what it's like and it's easy for them to recommend reduced use of pain relievers.

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