The 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.
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
As 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.