Chronic pain, opioids and the ‘false dream of mass anesthesia’
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For more than a decade, the medical community as a whole, and particularly the field of rheumatology, has been trying to move away from opioids for the management of chronic pain — with varying degrees of success.
However, for a growing number of medical experts — in rheumatology and elsewhere — a completely new paradigm and understanding of pain, and its management, is needed. According to these sources, this new understanding should focus on and accept the reality that many patients with chronic pain are already facing — that living pain-free is an unrealistic goal that only serves to further their despair when it is not achieved.
Image: Haider J. Warraich, MD
“In the United States, we have this notion that we have this God-given right to be pain-free,” Michael E. Schatman, PhD, CPE, a clinical instructor at the New York University Grossman School of Medicine’s Department of Anesthesiology, Perioperative Care and Pain Medicine, and editor-in-chief of the Journal of Pain Research, told Healio Rheumatology. “But that is clearly an unrealistic goal, particularly for patients with chronic conditions.”
Nevertheless, many physicians thought they had achieved that goal in the 1990s, with the push toward using opioids for chronic pain management. The release of OxyContin (oxycodone, Purdue Pharma) in 1995 sparked an explosion of opioid prescriptions throughout the U.S. That drug would go on to become a blockbuster, generating $35 billion in revenue. What occurred over the next 20 years has been the subject of countless articles and studies. From 1999 to 2014, more than 165,000 people in the U.S. died of opioid medication overdose, according to the CDC. In 2013 alone, an estimated 1.9 million people abused or were dependent on prescription opioid drugs.
As recently as 2019, studies have suggested that nearly 27% of patients with osteoarthritis still receive opioids and benzodiazepines, with about 36% of such individuals demonstrating at least one risk factor for prescription misuse. Meanwhile, during 2014 to 2015, nearly one-third of patients with systemic lupus erythematosus in a Michigan-based cohort used prescription opioids, with about two-thirds of those users doing so for more than 1 year.
There is no doubt that opioids are flawed medications. That said, understanding where they may continue to be used and how they may fit into multimodal treatment paradigms for pain management remains uncertain.
In many ways, rheumatologists are back at square one. Patients hurt, and while there are drugs to treat them, those drugs — opioids, anti-inflammatories, NSAIDs, acetaminophen and tramadol alike — are all less than perfect.
It is for this reason that experts like Haider J. Warraich, MD, director of the Heart Failure Program at the Veterans Affairs Boston Healthcare System, associate physician at Brigham and Women’s Hospital, and author of the book The Song of Our Scars: The Untold Story of Pain, believe that it is necessary to look beyond pharmacotherapies in helping patients feel better.
“The first thing all physicians need to do is teach their patients to accept that they must learn to live with pain,” he said. “They should prioritize living their life to the fullest, rather than trying to control the pain at all times.”
This mindset often goes hand-in-hand with basic wellness behaviors like exercise and sleep hygiene, and has gained traction among doctors of all stripes.
“The biggest change in our thinking regarding pain management has been the tremendous increase in the evidence base for a plethora of non-pharmacological therapies,” Daniel Clauw, MD, professor of anesthesiology, psychiatry and rheumatology at the University of Michigan Medical School, said in an interview.
Clauw noted a growing body of data in support of strategies ranging from cognitive behavioral therapy (CBT) to yoga.
“These approaches that were heretofore considered complementary and alternative are now being called integrative since they have been shown to be effective and safe,” he said.
Although such methods have gained more widespread use, many physicians believe medications should continue to play a role in pain management. And, yes, that can include opioids.
“I have spent most of my career taking people off opioids, and I have seen the shift from opiophilia to opiophobia,” Schatman said. “There has to be a sane middle ground.”
According to Schatman, there are approximately 50 million people who experience chronic pain in the United States, 20 million of whom demonstrate what he called “high-impact” pain.
“If I can put a patient on a low dose of opioids, monitor them so they use them responsibly, and get them to a place where the pain has a low impact on how they live, I have been successful,” he said. “Suddenly, they have regained quality of life, where they can get back to work or hold their 1-year-old grandchild.”
This is the goal of every rheumatologist — to give their patients a better quality of life. However, finding the balance between drugs and wellness to reach that goal is no easy task. Recommendations from organizations like the CDC have provided guidance for some, but have also raised additional questions.
‘Vilified’ Drugs
The CDC initially published a guideline for prescribing opioids for chronic pain in MMWR Recommendations and Reports and the Journal of the American Medical Association in 2016, and then updated the document in MMWR Recommendations and Reports in 2022, expanding the scope to include acute and subacute as well as chronic pain.
Deborah Dowell, MD, MPH, chief clinical research officer in the Division of Overdose Prevention at the CDC’s National Center for Injury Prevention and Control, was the first author of both of those documents, each of which outlined 12 recommendations for the use of opioids in pain.
In keeping with the trend toward wellness as a sensible approach to chronic pain, some of the aforementioned non-pharmacologic modalities top the list of recommendations, along with specific suggested dosing levels for opioid use.
“Many patients do not experience benefit in pain or function from increasing opioid dosages to 50 [morphine milligram equivalents per] day but are exposed to progressive increases in risk as dosage increases,” Dowell and colleagues wrote in the 2022 paper. “Therefore, before increasing total opioid dosage to 50 [morphine milligram equivalents per] day, clinicians should pause and carefully reassess evidence of individual benefits and risks.”
However, the authors did acknowledge that dosing levels may increase in certain situations.
“Clinicians should carefully evaluate a decision to increase dosage after an individualized assessment of benefits and risks, weighing factors such as diagnosis, incremental benefits for pain and function relative to risks with previous dosage increases, other treatments and effectiveness, and patient values and preferences,” Dowell told Healio Rheumatology.
She added that physicians should keep in mind that the risks associated with opioids, including overdose, rise with increased dosages.
“When opioids are needed, clinicians should generally avoid unnecessary dosage increases, use caution when increasing opioid dosages, and increase dosage by the smallest practical amount because overdose risk and other risks increase with increases in opioid dosage,” Dowell said.
Schatman broadly agreed that caution is warranted with opioid prescriptions and that dosages should not be increased without weighing individual benefits and risks. However, he stressed that such guidelines are not applicable to all cases.
“Guidelines are only so valuable — they are not the Bible,” he said, adding that the 2016 document in particular “vilified” opioids for both clinicians and the general public. The fear and panic surrounding drugs may have set the management of chronic pain back rather than moving the ball forward, he argued.
Regarding specific concerns with the guidelines, Schatman pointed to the use of morphine equivalents per day as a benchmark for dosing.
In an editorial by Fudin and colleagues in the Journal of Pain Research, for which Schatman was a co-author, he described these concerns.
“Since potency, receptor-binding affinity, physical tolerance, and various pharmacokinetic attributes differ among opioids, the concept of [morphine equivalent daily dose] was employed to justify transitioning from a currently prescribed opioid to one or more opioid equivalents,” they wrote. “However, the defined daily dosage (DDD) of one opioid does not necessarily exhibit the same effects of the DDD of another opioid.”
The authors of the MMWR paper themselves wrote that the use of the morphine equivalent dosing tool as a measure for opioid prescribing should be reconsidered in both the research and clinical settings. This speaks to larger concerns about the way opioids have been studied, and the way the CDC has addressed the available body of research.
Call for ‘Rheumatology-Specific’ Recommendations
In an editorial published in the Journal of Pain Research, Schatman and Ziegler interrogated the methods the CDC employed in developing its recommendations.
“What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem, but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose,” they wrote.
According to Schatman, many of the studies exploring opioid addiction rates and patterns are clinically inaccurate.
For example, he took issue with the conventional thinking that if a patient asks for an opioid by name, it is likely to be an indicator of dependence or addiction.
“I like when patients ask for a medication by name because it tells me that they are well-informed,” he said.
The CDC has also acknowledged that there are significant gaps for the research community to consider.
“No validated, reliable way exists to predict which patients will experience serious harm from opioid therapy and which patients will benefit from opioid therapy,” Dowell and colleagues wrote in the 2022 paper.
Schatman argued that if there is one way to employ these drugs more effectively, it would be to write “rheumatology-specific” guidelines for opioid use. Such a document could tailor approaches, prescriptions and dosing levels to the myriad conditions and types of pain that patients with rheumatic diseases experience, he added.
To that point, Dowell noted that the CDC included some content relevant for the rheumatology patient population in the 2022 paper.
“Specific to patients with rheumatologic conditions, the guideline notes that diagnosis can help identify disease-specific interventions to reverse, ameliorate or prevent worsening of pain and improve function, such as immune-modulating agents for rheumatoid arthritis,” she said.
In addition, the guideline highlights interventional approaches that may be employed in the clinic, according to Dowell.
“These include arthrocentesis and intra-articular glucocorticoid injection for pain associated with RA or osteoarthritis and subacromial corticosteroid injection for rotator cuff disease, which can provide short-term improvement in pain and function to supplement or facilitate exercise, physical therapy and other conservative approaches,” she said.
Meanwhile, regardless of what the recommendations suggest, many experts, including Clauw, believe that opioid use in rheumatology remains too high.
“There is little evidence that opioids are effective to treat chronic pain, and much evidence suggesting that they do significant harm,” he said.
Although many providers believe the biggest concern with opioids is addiction, Clauw sees this as just one issue among many others.
“They think that if their patients are not addicted, they are not having a problem with the opioid,” he said. “But opioids can also lead to tremendous increases in all-cause mortality by increasing risks for death from accidents or falls, suicides, myocardial infarctions and other such outcomes.”
What is clear is that more study of all aspects of opioid therapies is needed, from risk-benefit analyses to the likelihood of dependence or addiction. As researchers and clinicians wrestle with these topics, a closer look at some other types of pain medications may provide answers.
‘Easier to Give a Pill’
Schatman provided a list of drugs other than the former blockbuster OxyContin that have been used in the chronic setting — each with its own unique problems.
“Morphine is cleaner for parenteral use than most of the opioids out there,” he said. “This is not really an option for patients with chronic conditions, though, at least in part because many patients have allergies to morphine.”
Tramadol, meanwhile, binds “weakly” with mu opioid receptors, according to Schatman.
“It is a schedule 4 rather than a schedule 2 drug, so some physicians are more comfortable prescribing it,” he said.
It should be noted that many patients being treated with tramadol are also receiving selective serotonin reuptake inhibitors (SSRIs), Schatman added.
“Serotonin syndrome can be fatal,” he said.
According to Warraich, neither morphine nor tramadol can be considered long-term solutions to chronic pain in the rheumatology space.
“I do not think the solution to the chronic pain crisis is to replace one opioid with another,” he said. “Morphine and tramadol are both opioids.”
Turning to less potent medications, the issue with acetaminophen and NSAIDs is that they are most effective in the short-term for mild-to-moderate pain, but not for the types of chronic pain patients with rheumatic diseases can experience.
“When opioids became verboten, there was some movement toward NSAIDs,” Schatman said. “But when you prescribe a class of medications that is FDA-approved only for mild-moderate pain to patients with severe pain, on top of dealing with their potentially dangerous iatrogenesis, their lack of analgesic efficacy in this unfortunate group is hardly surprising.”
Although acetaminophen and NSAIDs can be purchased over the counter and are largely considered safe, Warraich stressed that this perception belies another reality.
“They can cause bleeding from the intestines, renal failure and heart failure,” he said. “Those are all serious concerns.”
Despite this flawed armamentarium, Schatman is optimistic that solutions are on the horizon, largely because of the expertise of rheumatologists.
“They are the scientists of pain doctors,” he said.
This science-based approach has led to the development of biologics, which not only treat the inflammatory aspects of chronic conditions, but can also consequently minimize pain, according to Schatman.
“These drugs continue to be developed and refined,” he said.
That said, biologics are not perfect, and many patients who use them continue to progress in their disease and experience ongoing pain.
This is where opioids can and should come into play, Schatman argued.
“Doctors want to prescribe opioids to patients when they feel particularly bad or when other approaches are not working, but, in many places, they are unable to do this because of regulatory crackdowns,” he said.
These physicians face the unappealing choice of prescribing one type of ineffective pill that carries adverse events and complications, or another.
“It is often easier to give a pill, not because they are better, but because they are more readily available,” Warraich said. “This is another symptom of what is wrong with our health care system and the way we approach these complex problems.”
Regardless of the drug being used, Warraich stressed that it is important for clinicians to move away from the idea that pills are the cure for pain, and instead toward the idea that seemingly abstract notions like “joy” and “kindness” can be profoundly beneficial. Here, Warraich represents an increasing number of physicians who are trying to employ psychological approaches to physical problems.
‘Complex Phenomenon’
In a comprehensive review paper published in Current Pain and Headache Reports, Mathias and colleagues found that a host of non-pharmacological, pharmacological, interventional, and surgical strategies can suppress inflammation and provide analgesia for patients with chronic pain. Moreover, these patients frequently benefitted from “behavioral and psychological treatment options” that can minimize pain and improve functionality.
“Pain is a very complex phenomenon,” Warraich said. “One of the mistakes we have made in medicine is to consider pain to be a purely physical sensation. It is much more complex than that and has significant emotional elements, including prior trauma and traumatic memories.”
Previous and current injuries, as well as chronic physical ailments, all can cause fear. This fear, in turn, can cause or be associated with pain. Integrative treatments like mindfulness, meditation, acupuncture, acupressure, yoga and tai chi, among others, have had significant utility in minimizing this fear, according to Warraich.
“What these therapies do is eliminate and overcome the fear people have about pain,” he said.
Clauw added that these interventions also compare favorably to analgesics in terms of effect sizes and adverse events.
“They all have effect sizes comparable to any class of analgesic drug, but have much fewer side effects,” he said.
Historically, one challenge regarding uptake of many of these integrative approaches is access. Outside of urban areas and far away from major academic medical centers, it may be difficult to find an expert in mindfulness or someone to teach tai chi.
However, this may be changing, according to Leonard H. Calabrese, DO, professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic. Here, online communities have been rising to fill these gaps in access, he said.
“There are communities of patients online who are reaching out to each other and providing all kinds of resources,” Calabrese said, encouraging clinicians in areas where access is an issue to point their patients toward these resources whenever possible.
However, there are other actions every rheumatologist can take, apart from prescribing drugs, to help patients get through life with their pain — and it begins with understanding the subject.
‘Change the Narrative’
In a paper published in ACR Open Rheumatology, Falasinnu and colleagues described chronic pain in rheumatology as “heterogeneous.” They noted that “overlapping” pain conditions can impact patients with psoriatic arthritis, RA, Sjögren’s syndrome, systemic lupus erythematosus and systemic sclerosis, among other conditions.
“Our findings suggest that [chronic overlapping pain conditions] are strikingly common among patients with rheumatic disease and are associated with lower quality of life and greater health care needs,” Falasinnu and colleagues wrote.
According to Calabrese, the realities of chronic pain in rheumatology mean that physicians and patients alike must reconcile with the possibility that said pain may never completely disappear.
“When patients have chronic pain from a source — regardless of whether it is a headache or back ache or some other place — the chances of it just magically going away are diminishingly small,” Calabrese, who is also chief medical editor of Healio Rheumatology, said in an interview. “If the motivation for the patient is, ‘How and when am I going to get rid of this pain?’ then the outcomes will be suboptimal. We need to change the narrative.
“We need the goal for patients to be: ‘How am I going to live my life with this?’” he added.
According to Calabrese, the initial approach toward this goal is “deep listening,” to better understand the nature of the patient’s suffering.
“It does not take much to recognize that people who live in chronic pain are fearful about the future and how they are going to make their way in the world,” he said.
Warraich, meanwhile, added that one of the greatest tools every physician has is showing empathy.
“Small gestures to recognize what the patient is going through can be effective and long-lasting,” he said.
Calabrese described empathy as a “superpower” that can be wielded by any physician anywhere.
“I let patients know that this pain and suffering is not in their head, not their fault and not caused by some kind of mental weakness on their part,” he said. “When I tell them this, it is often met by a sense of great relief.”
The next step is to encourage patients to do things that bring them joy, “even if it means they hurt physically,” Warraich said.
“I try to convey that trying to reach the goal of a completely pain-free life can actually lead patients to experience more pain,” he added.
Admittedly, this can be a difficult message to convey. Calabrese suggested that one way to explain it is to draw a distinction between concerns and complaints.
“They have legitimate concerns about how their life is going to progress, and these concerns need to be validated,” he said.
The next consideration is to talk about the pills the patient has taken. Like other rheumatologists, Calabrese has seen a variety of biologics that improved pain and function, as well as those that have demonstrated suboptimal outcomes.
“Try to avoid saying, ‘You failed on this biologic,’” he said. “Rather say, ‘I hear you,’ and, ‘Let’s figure this out together.’”
In short, rheumatologists must walk the line between acknowledging the psychological aspects of chronic pain without victim-blaming.
“There used to be huge stigma around depression, anxiety and other mental health issues, but we have come a long way in that regard,” Warraich said. “We aspired to huge cultural change in mental health outcomes, and that change is happening. We need to do the same with chronic pain.”
Warraich acknowledged that none of this will be easy. However, he is optimistic that the needle is moving in the right direction.
“Medicine has given the false dream of mass anesthesia,” he said. “Allowing people to believe that dream has led to a lot of harm. We have to be honest with our patients that they are going to hurt, and we need to teach them that they can live better despite the pain.”
- References:
- Alamanda VK, et al. Arthritis Care Res. 2019;doi:10.1002/acr.23933.
- Dowell D, et al. JAMA. 2016;doi:10.1001/jama.2016.1464.
- Dowell D, et al. MMWR Recomm Rep. 2022;doi: 10.15585/mmwr.rr7103a1.
- Falasinnu T, et al. ACR Open Rheum. 2022;doi:10.1002/acr2.11488.
- Fudin J, et al. J Pain Res. 2016;doi: 10.2147/JPR.S107794.
- Mathias K, et al. Curr Pain Headache Rep. 2021;doi:10.1007/s11916-021-00973-0.
- Schatman ME, Ziegler SJ. J Pain Res. 2017;doi:10.2147/JPR.S153322.
- Somers EC, et al. Morb Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6838a2.
- For more information:
- Leonard H. Calabrese, DO, can be reached at 9500 Euclid Ave., Cleveland, OH; email: calabrl@ccf.org.
- Daniel Clauw, MD, can be reached at 1500 E. Medical Center Dr. UH1 H247, SPC 5048, Ann Arbor, MI 48109; email: dclauw@med.umich.edu.
- Deborah Dowell, MD, MPH, can be reached at 4770 Buford Highway, NE, MS S106-8; Atlanta, GA 30341; email: zvq5@cdc.gov.
- Michael E. Schatman, PhD, CPE, can be reached at 550 First Ave., New York, NY 10016; email: michael.schatman@nyulangone.org.
- Haider J. Warraich, MD, can be reached at 70 Francis St., Boston, MA 02115; email: hwarraich@parters.org.
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