Painkillers Cause Chronic Pain? Rats!!!

By Pat Anson, Editor

A provocative new study is likely to stir fresh debate about the risks associated with opioid pain medication. It’s not another study about addiction or overdose, but whether opioids actually increase chronic pain, a condition known as hyperalgesia. 

An international team of researchers found that even just a few days of morphine can make chronic pain last for several months by intensifying the release of pain signals in the spinal cord.

But there’s a catch. The research was conducted on laboratory rats.

"We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain," said Peter Grace, PhD, an assistant research professor at the University of Colorado-Boulder's Department of Psychology and Neuroscience. "We found the treatment was contributing to the problem."

Grace and his colleagues found that damaged nerve cells in rats send a message to spinal cord immune cells known as glial cells, which normally act as "housekeepers" to clear out unwanted debris and microorganisms. The first signal of nerve pain sends glial cells into alert mode, priming them for further action.

"I look at it like turning up a dimmer switch on the spinal cord," said Grace.

Nerve pain was induced in the rats by slicing open their thighs. A fine thread was then tied around a major nerve. Over the next three months, researchers poked the rats' paws with stiff nylon hairs to see how sensitive they were to pain.

Injured rats that were not treated with morphine eventually recovered and did not show pain, but those that were treated with morphine for five days remained sensitive to pain. Researchers believe the morphine stimulated their glial cells and sent them into overdrive. They liken the effect to being slapped in the face twice.

"You might get away with the first slap, but not the second," said co-author Linda Watkins, a Distinguished Professor at CU Boulder. "This one-two hit causes the glial cells to explode into action, making pain neurons go wild."

"The 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," said Watkins. "This is a very ugly side to opioids that had not been recognized before."

Patient advocates had a mixed reaction to the study.

“Linda Watkins is doing some awesome work. We know that glial cells are the key to pain generation. Exactly how is still poorly understood,” said Terri Lewis, PhD, a rehabilitation specialist who teaches in the field of Allied Health.  “We know that 'something' triggers inflammation and maintains it. When that trigger is turned up high, glial cells are activated."

“Generalizing from rats to humans is not okay. But if the same results are found in pigs, there is probably something to talk about,” added Lewis.

“There is enough evidence in humans that opioids work and do not make pain worse,” said Janice Reynolds, a retired nurse and patient advocate.  “Even the work in hyperalgesia has not, contrary to claims by opiophobics, translated well from rats to humans. The write up is extremely negative and tends to lead one to believe the results may be slanted or even poorly interpreted. The fact they are singling ‘chronic pain’ out is a warning sign.”

The CU-Boulder study, which is published online in the Proceedings of the National Academy of Sciences, does have an impressive pedigree, including researchers at the University of Adelaide in Australia, the University of North Carolina, the Chinese Academy of Sciences, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Tsinghua University in Beijing.

The study was funded in part by the American Pain Society, Australia's National Health and Medical Research Council, the National Natural Science Foundation in China, the National Institute on Drug Abuse, the National Institute of Dental and Craniofacial Research and the National Institute of Alcohol Abuse and Alcoholism.

Study: Some Brains ‘Hardwired’ for Chronic Pain

By Pat Anson, Editor

Why do some people develop chronic pain from an injury or illness, while others do not?

The answer to that question may really be all in our heads.

A groundbreaking study by scientists at Northwestern University and the Rehabilitation Institute of Chicago (RIC) found that some people are genetically predisposed to chronic pain because of brain “abnormalities” that raise their risk of developing chronic pain. The findings challenge long-standing views on the science of pain, which emphasize treating pain at the site of the initial injury.

"While simple, the logic of addressing problems at the site of an injury to remove pain has resulted in only limited success," said senior study author Marwan Baliki, PhD, a research scientist at RIC and an assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

"The central processes of chronic pain have largely been ignored, so our research team set out to better understand the brain's role."

Baliki and his colleagues conducted the first longitudinal brain imaging study, which tracked 159 patients for three years following an acute back injury, along with 29 healthy control subjects.  

MRI brain scans were conducted on all of the participants five times during the course of the study.

The researchers found that patients who developed chronic pain from their back injury had a smaller hippocampus and amygdala compared to those who recovered from the injury and the healthy control subjects.

The hippocampus is the primary brain region involved in memory formation and retention, while the amygdala is involved in the processing of emotions and fear. In addition to size variations, these brain regions also showed differences in connections to the rest of the brain, particularly to the frontal cortex, an area involved in judgment.

Together, the researchers estimate that these brain differences accounted for about 60% of the chronic pain felt by participants.

Most importantly, the study also revealed that the volumes of the amygdala and hippocampus did not change over the course of the study, suggesting that those who developed chronic pain were genetically predisposed to it.  

"Here we establish that the gross anatomical properties of the corticolimbic brain, not the initial back pain, determine most of the risk for developing chronic pain," said first author Etienne Vachon-Presseau, PhD, a visiting postdoctoral fellow in physiology at Feinberg.

“As the anatomical risk factors were stable across 3 years, they were presumably hardwired and present prior to the event initiating back pain. These results pave the way for the development of novel and distinct approaches to prevention and treatment of chronic pain.”

The Northwestern and RIC study will be published in the June edition of the journal Brain.

Talking Turkey: How Food Plays a Role in Pain

By Pat Anson, Editor

There’s a nugget of truth to the old saying, “You are what you eat.” And no, we don’t mean chicken nuggets. We’re talking turkey.

Researchers at Brigham and Women's Hospital in Boston say changes in diet and gut bacteria appear to influence the activity of brain cells involved in controlling inflammation and neurodegeneration. They’ve published their study in the journal Nature Medicine

"For the first time, we've been able to identify that food has some sort of remote control over central nervous system inflammation," said corresponding author Francisco Quintana, PhD, an investigator in the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital.

"What we eat influences the ability of bacteria in our gut to produce small molecules, some of which are capable of traveling all the way to the brain. This opens up an area that's largely been unknown until now: how the gut controls brain inflammation."

While studying laboratory mice, Quintana and his colleagues found that gut bacteria produce molecules that influence astrocytes -- star-shaped cells that reside in the brain and spinal cord.

The molecules, which are derived from tryptophan (an amino acid found in turkey and other foods), act as fuel that helps the astrocytes limit brain inflammation.

In blood samples from patients with multiple sclerosis (MS) – a disease that attacks the body’s central nervous system -- the researchers found lower levels of these tryptophan-derived molecules.

"Deficits in the gut flora, deficits in the diet or deficits in the ability to uptake these products from the gut flora or transport them from the gut -- any of these may lead to deficits that contribute to disease progression," said Quintana.

MS is a chronic and incurable disease that causes numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain.

In addition to turkey, tryptophan is found in other high-protein foods such as chicken, beef, nuts and cheese. Its a myth that eating lots of turkey will put you to sleep, according to the American Nutrition Association. But tryptophan does help produce serotonin, a neurotransmitter that regulates mood and mental activity,

Scientists are just beginning to recognize that food and gut bacteria play a role in multiple sclerosis and other chronic pain conditions.

Researchers at New York University’s Langone Medical Center recently found that some intestinal parasites and bacteria play a beneficial role in helping to balance the immune system, and reduce rates of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.

Sanitary practices have sharply reduced intestinal worm infections in developed nations, which now have some of the highest rates of Crohn’s and colitis. Scientists believe the worms help produce a certain type of bacteria that helps control inflammation. This “hygiene hypothesis” may also apply to MS, rheumatoid arthritis, type 1 diabetes, and other autoimmune diseases.

Study Finds Friendship ‘Stronger than Morphine’

By Pat Anson, Editor

People with more friends and large social networks have a higher tolerance for pain, according to a new study by researchers at Oxford University.

Scientists believe that social bonding activities such as music, dancing and laughter activate the body’s endogenous opioid system, releasing natural endorphins that not only make you feel better when seeing friends, but can also relieve pain.

“Endorphins are part of our pain and pleasure circuitry -- they're our body's natural painkillers and also give us feelings of pleasure,” says Katerina Johnson, a doctoral student at Oxford University, who is studying whether differences in neurobiology can explain why some people have larger social networks than others.

“To test this theory, we relied on the fact that endorphin has a powerful pain-killing effect -- stronger even than morphine.”

Johnson and her colleagues enrolled 107 healthy young adults in a squatting exercise to test their tolerance for pain. Participants were told to squat against the wall with their knees bent at a 90° degree angle, and to hold that position and endure the discomfort for as long as possible.

Questionnaires were also completed by the participants to measure their personality traits and physical fitness, and to see how often they interacted with friends.

Not surprisingly, people who were more fit were able to hold the squatting position longer. But so did people with larger social networks.  

“Obviously we had to bear in mind that fitter individuals may be able to endure this physical pain test for a longer length of time.  However, even when we take this into account, our results show that pain tolerance still significantly predicts network size,” Johnson wrote in an email to Pain News Network.

An unexpected finding was that fitter people in the study tended to have smaller social networks.

“It may simply be a question of time -- individuals that spend more time exercising have less time to see their friends. However, there may be a more interesting explanation -- since both physical and social activities promote endorphin release, perhaps some people use exercise as an alternative means to get their 'endorphin rush' rather than socializing,” she said.

Since only healthy people participated in the study, Johnson admits her research may not apply well to chronic pain patients. But since many pain patients are disabled and unable to work or participate in many social activities, there could be some lessons to learn.

“When considering chronic pain, it seems like it may be a vicious circle whereby the more an individual is in pain, the less interested they are in interacting socially with others and their smaller social networks may in turn result in reduced activity of the endorphin system (thereby worsening their pain).  Perhaps also individuals that are genetically predisposed to reduced endorphin activity (and lower social motivation) are more likely to develop chronic pain conditions,” Johnson wrote.

“Another finding of our study was that individuals with smaller social networks tend to be more stressed, and stress is also thought to exacerbate pain.  However, clearly the underlying neurochemistry in pain responses is complex, though the endorphin system is heavily implicated in pain responses given its potent analgesic properties.”

The study findings are reported online in the journal Scientific Reports. 

What Does Your Pain Feel Like?

By Pat Anson, Editor

Does your chronic pain feel like you’ve been hit with a hammer, a bad sunburn that won’t go away, or ants crawling under your skin?

Those are some of the choices patients have in a new campaign launched in Ireland to change the way patients describepain to their physicians.   

Accurately assessing pain is difficult because pain is so subjective. For many years doctors have relied on various versions of the Wong Baker Pain Scale – a series of sad and smiling faces a patient chooses from to help their doctor understand how much pain they are in. The scale is so simple it was originally developed for children, but is now used around the world for adults.

The “Mypainfeelslike…” campaign aims to improve on that method by using more descriptive images and phrases to help doctors understand and diagnose their patient’s pain. The campaign focuses on neuropathic pain, but can be used for many other types of chronic pain. The initiative is sponsored by Grunenthal Group, a German pharmaceutical company.

Instead of an unhappy face, patients can choose from a dozen images, ranging from a burning flame to a rope tied in knots to a set of ice cubes. They also fill out a questionnaire and select different phrases to describe their pain, such as “a hot iron on my skin” or “a volcano erupting.”

Patients are also asked to fill out a questionnaire to select different phrases to describe their pain, such as “a hot iron on my skin” or “a volcano erupting.” And there's a list of multiple choice answers to describe how pain affects their ability to work, exercise and socialize.

It may take a few minutes to complete the questionnaire, but the idea is to get patients to “invest more time and accurateness in thinking about their symptoms, describing them more precisely, and preparing for doctors’ appointments.”

“Doing so forces us to reconsider our chronic pain, and the different ways that we feel it. This improves our self-awareness, allows us to better communicate our situation, and helps us get the most value out of the very short time that we usually have during doctors’ appointments,” the website says.

To take the questionnaire, click here.

According to a survey by Grunenthal, over half of Irish pain sufferers feel frustrated when trying to communicate their pain to a doctor. Over a quarter say they delay discussing their pain because they’re not sure how to do it.

“Living with chronic or nerve pain affects people’s well-being, their ability to be independent, their productivity and relationships, which can lead to feelings of depression," John Lindsay, chair of Chronic Pain Ireland told the Irish Independent.  “The ‘Mypainfeelslike…’ campaign will help raise awareness of the impact of chronic pain and give people living with this disease the tools to re-evaluate their pain management plans.”

Does Washing Your Hands Raise Risk of IBD?

By Pat Anson, Editor

Many of us were taught as children to always wash our hands before leaving the bathroom and before meals. But that basic sanitary practice may be contributing to an increase in inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis, according to a new study published in the journal Science.

Researchers at New York University’s Langone Medical Center tested the so-called “hygiene hypothesis” – the theory that some intestinal parasites and bacteria are beneficial because they help balance the immune system and reduce IBD rates. Sanitary practices have sharply reduced gut worm infections in developed nations, which now have some of the highest rates of Crohn’s disease and ulcerative colitis.

“Our findings are among the first to link parasites and bacteria to the origin of IBD, supporting the hygiene hypothesis,” says parasitologist P’ng Loke, PhD, an associate professor at NYU Langone.

“The prevalence of IBD is much less in regions of the world which have heavy worm infection. In fact, I got interested in the question of how worms can be beneficial when I was contacted by an individual who had deliberately infected himself with worms to treat his symptoms of IBD and was able to put his disease into remission.”

Loke and his colleagues found that laboratory mice infected with intestinal worms experienced a thousand-fold decrease in Bacteroides — a type of bacteria linked to people with higher risk of IBD. At the same time, the number of Clostridia, a bacterium known to counter inflammation, increased tenfold in the mice.

RESEARCHERS P'ng Loke and Ken Cadwell, NYU Langone Medical Center

Researchers believe the immune response to the worms triggers the growth of Clostridia, which then either outcompete Bacteroides for nutrients or release toxins that are harmful to them.

In a second phase of the study, researchers gave mice an infusion of Clostridia – without the use of parasites – and found that it reduced the presence of Bacteroides.

“That gives us a lot of hope in terms of IBD therapy because maybe we don’t need to give people parasitic worms, which can be harmful and cause disease, and instead target the harmful bacteria by replacing them with healthy bacteria,” says microbiologist Ken Cadwell, PhD, an assistant professor at NYU Langone and the Skirball Institute of Biomolecular Medicine. “Our study could change how scientists and physicians think about treating IBD.”

Researchers say the hygiene hypothesis may also apply to other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, in which processes meant to attack foreign invaders instead become oversensitive and trigger an immune response to the body’s own cells.

IBD is a chronic or recurring immune response and a painful inflammation of the gastrointestinal tract. Inflammation affects the entire digestive tract in Crohn’s disease, but only the large intestine in ulcerative colitis.

According to the Crohn's and Colitis Foundation of America, IBD affects about 1.6 million Americans and tends to run in families. Caucasians are more likely than other ethnic groups to have IBD. The diseases are especially prevalent in Jews of European descent (Ashkenazi Jews). African Americans and Hispanics in the United States are also increasingly affected.

CRPS Patients Needed for Clinical Study

By Pat Anson, Editor

About 80,000 Americans each year are diagnosed with Complex Regional Pain Syndrome (CRPS), a poorly understood condition caused by injury or trauma that leads to throbbing and burning pain that never goes away. It often takes years and multiple doctors before a patient is diagnosed with CRPS – and by then the pain has often migrated to other parts of the body and has become chronic.

That’s the dilemma now faced by Axsome Therapeutics (NASDAQ: AXSM), a biopharmaceutical research company that hopes to win FDA approval for an experimental, non-opioid drug that would be the first medication of any kind approved for treating CRPS --- also known as Reflex Sympathetic Dystrophy (RSD).

Axsome is conducting a Phase 3 clinical study of the drug --- called AXS-02 --- in the United States, Canada, the United Kingdom and Australia.

The challenge? Although Axsome only needs about 190 patients for the CREATE-1 study, it’s having trouble finding enough eligible patients. They’re looking for patients who suffered their initial injury in the last year and who were diagnosed with CRPS in the last six months.

“We’re trying to find patients very early in the stages of CRPS,” says Randall Kaye, MD, chief medical officer of Axsome.  

It typically takes a year or more for a patient to get a CRSP diagnosis because its early symptoms are not all that different from acute pain caused by surgery, a broken bone or some other type of trauma. It takes an experienced doctor to recognize the early signs.

“These are patients who continue to have pain that just doesn’t quite follow the routine course. Even after about a week or two, something is different. The pain is too much or the quality of the pain is just different. They describe a burning sensation or there’s exquisite sensitivity to temperature,” says Kaye. “What happens to these patients is that they continue to see a variety of physicians before they’re given that label of CRPS.”

a CRPS PATIENT 6 MONTHS AFTER leg fracture

“I wish it was easy to diagnose Complex Regional Pain Syndrome,” says Barby Ingle, president of the International Pain Foundation (iPain), who was diagnosed with RSD/CRPS two years after a car accident that injured her shoulder. “I went from having RSD in my face and shoulder. It then spread to my right arm and hand, then my entire right side. By the time I was properly diagnosed I had full body including organ involvement.”

“I have personally spoken to thousands of patients who have been diagnosed with RSD/CRPS. Out of all of them, two were diagnosed within the first 3 months, most took over a year. For me, I saw 43 providers before receiving a proper diagnosis. Most pain providers were not educated and although providers are getting better education now, there are still major delays.”

Opioids and other pain medications only dull the pain of CRPS, but Axsome is hoping that AXS-02 can also treat the underlying condition that causes the disorder.

“I hope so,” says Kaye. “Instead of just relieving pain, we’re getting right at the underlying pathophysiology of the condition.”

AXS-02 is an oral formulation of zoledronic acid, an injectable bisphosphonate that inhibits the production of compounds that cause bone pain. Bisphosphonates have long been used to treat osteoporosis and Kaye believes they might also stop the progression of CRPS.

“It’s pretty straightforward. Patients take one tablet once a week for six weeks and they’re done,” Kaye told Pain News Network. “We don’t think there will be a reoccurrence based on the mechanism of action. But we want to be sure.”

Proving that AXS-02 can do more than just relieve symptoms of CRPS will take time. If it can find enough patients, Axsome hopes to finish the CREATE-1 study in mid-2017. Additional studies may then be needed. If the clinical results are positive, the Food and Drug Administration has granted “fast track” and “orphan drug” designation for AXS-02, which will speed up the application and approval process.

CRPS patients interested in applying for the CREATE-1 study should click here.    

Survey Finds Racial Bias in White Medical Students

By Pat Anson, Editor

New research has founds signs of racial bias and ignorance about issues involving pain management in a survey of white medical students.

Researchers at the University of Virginia asked 222 medical students and residents a series of hypothetical questions about treating pain in mock medical cases involving white and African-American patients suffering pain from a kidney stone or leg fracture. They were also asked whether statements about biological differences between blacks and whites were true or untrue.

Many of the students and residents were found to hold false beliefs, such as believing that black people's skin is thicker and that their blood coagulates faster than whites. 

Half of those surveyed endorsed at least one false belief; and those who did were more likely to report lower pain ratings for black patients and were less accurate in their treatment recommendations for blacks.

Medical students and residents who did not endorse false racial beliefs did not show the same treatment bias. 

"Many previous studies have shown that black Americans are undertreated for pain compared to white Americans, because physicians might assume black patients might abuse the medications or because they might not recognize the pain of their black patients in the first place." said Kelly Hoffman, a psychology PhD candidate who led the study. "Our findings show that beliefs about black-white differences in biology may contribute to this disparity."

The findings are published in the journal Proceedings of the National Academy of Sciences.

"We've known for a long time that there are huge disparities in how blacks and whites are assessed and treated by the medical community," Hoffman said. "Our study provides some insight to what might contribute to this -- false beliefs about biological differences between blacks and whites. These beliefs have been around for a long time in our history.

"What's so striking is that, today, these beliefs are not necessarily related to individual prejudice. Many people who reject stereotyping and prejudice nonetheless believe in these biological differences. And these beliefs could be really harmful; this study suggests that they could be contributing to racial disparities.

Previous research has shown that African-Americans are systematically undertreated for pain compared to white Americans, and that blacks are less likely to be prescribed opioid pain medication than whites.

A 2012 study published in The Journal of Pain found that blacks, especially young adults, had significantly more pain and disability whether they lived in lower or higher socioeconomic neighborhoods.

The Good and Bad About a Pain-Free Statin

By Pat Anson, Editor

New research has confirmed what a lot of us already know about statins: the cholesterol fighting drugs may lower your risk of heart disease, but they can also cause painful muscle cramps, memory loss and other side effects.

In the first major trial of its kind, researchers at the Cleveland Clinic gave atorvastatin (Lipitor) or a placebo to nearly 500 patients with very high cholesterol levels, many of whom had a history of muscle related statin intolerance. Over 42 percent of the patients reported muscle pain or weakness on atorvastatin.  

Those patients were then enrolled in another phase of the study and given a non-statin drug called evolocumab, which inhibits a protein in the liver (PCSK9) that helps produce cholesterol.  

The good news? Evolocumab was very effective in lowering cholesterol and rarely produced muscle problems.

The bad news? Evolocumab would cost about $14,000 a year and is self-administered monthly by injection only. Double ouch.

"Statin intolerance has been a very challenging clinical problem," said Steven Nissen, MD, chairman of Cardiovascular Medicine at Cleveland Clinic. "The study showed that PCSK9 inhibitors can significantly lower cholesterol in patients with documented statin intolerance, providing an effective treatment for these difficult to manage patients."

While the study findings, published in JAMA, were mainly meant to test the efficacy of evolocumab, it’s nice to see the medical community acknowledge that statins have painful side-effects and that drug makers are trying to find alternatives.

I started taking statins over a decade ago on the recommendation of a family physician, because of mildly elevated cholesterol and a scary family history of coronary artery disease. Right away I started having painful leg cramps at night, and during the day I felt lethargic and less alert.  My doctor was a bit skeptical and switched me from one statin to another (Lipitor, Vytorin and finally Crestor), but the cramps and brain “fogginess” continued. When I stopped taking statins, the symptoms disappeared.

I’m certainly not alone. Muscle pain is reported by an estimated 5% to 29% of statin users, but there are no blood or diagnostic tests to document muscle-related statin intolerance. It’s also hard to fight conventional thinking (and extensive advertising) that statins are good for you, so a lot of patients are encouraged to keep on taking them, even if they do cause pain.

Only in 2014 did the Food and Drug Administration require warning labels on statins, cautioning that some statins can cause a muscle injury called myopathy, which is characterized by muscle pain or weakness. In rare instances, the FDA says statins can also cause liver injury, diabetes and memory loss.   

The first statin, lovastatin, was approved by the FDA in 1987 – meaning it took the agency nearly three decades to start warning about these side effects. It’s only through patient complaints that the FDA even learned about them, a concept that the American College of Emergency Physicians (ACEP) should probably brush up on.

As Pain News Network has reported, ACEP wants Medicare to stop requiring hospitals to ask patients about the quality of their pain care. That's not a good idea. And the painful history of statins is proof of that.

How Opioid Prescribing Guidelines Use Pseudoscience

By Michael Schatman and Jeffrey Fudin, Guest Columnists

Recently, we (along with our colleague, Dr. Jacqueline Pratt Cleary) published an open access article in the Journal of Pain Research, entitled “The MEDD Myth: The Impact of Pseudoscience on Pain Research and Prescribing Guideline Development.”

In this work, we address the issue of how governmental and managed care opioid guideline prescribing committees use the flawed concept of morphine-equivalent daily dose (MEDD or MME) to arbitrarily place limits on the amount of opioids that a clinician “should” prescribe to any patient with chronic pain -- as if all patients were identical. 

The article cites excellent research that exposes the invalid concept of MEDD – and while guideline authors are fully aware of that lack of evidence, they are hypocritically fine with using MEDD as a device to thwart chronic opioid use. In the case of opioids for chronic non-cancer pain, there is at least some evidence.  But for MEDD, there is no evidence.   

One reason the MEDD concept is not legitimate is pharmacogenomic differences – that is, due to each of our unique genetic compositions, various individuals and geographical groups metabolize some opioid analgesics differently.  These differences are often enormous. 

For example, it may require Person “A” 20 milligrams of hydrocodone to achieve adequate pain relief, while Person “B” (of the same gender and weight) may require 60 milligrams of the same drug for the same type of chronic pain condition.  Does this make Person “B” an addict?  Of course not.

We believe that by arbitrarily limiting the “appropriate” amount of an opioid that a physician should prescribe to a patient (which all recent guidelines – including the CDC’s guideline – call for), physicians feel compelled to limit the amount of opioid analgesic therapy that they prescribe – irrespective of the amount of relief that a patient with chronic pain receives. 

Is this good pain medicine practice?  Hardly.  However, in the eyes of the anti-opioid zealots who have dominated recent opioid prescribing guideline committees, their agenda of taking opioids out of the picture altogether for patients with chronic pain is evidently more important than is patient well-being.

Aside from the pharmacogentic issues, we also have conversion issues because of simple mathematics.  We cite data that clearly shows there are no universally accepted opioid equivalents.  Even if there were no issues with genetic variability, there is still no consensus on how to mathematically convert one opioid to another. For example, the state of Washington may decide on a different MEDD equivalent than the one New York state chooses.

Will the anti-opioid zealots admit that they have a non-scientifically-based agenda to take opioids out of the American chronic pain management discussion?  No – because if they were to do so, they would be seen as cruel or uncaring.  Rather, they emphasize that their concerns are for the well-being of patients and society.  Their logic suggests that if clinicians stop prescribing opioid analgesics altogether, then the unfortunate number of opioid-related overdoses and deaths will decrease dramatically. 

Not surprisingly, they lack the data that supports this assertion, yet the data are clear that when this happens, heroin use increases proportionally. 

As scientists and practitioners who work with patients with chronic pain every day, we see the damage in which these guidelines result.  For example, while the guidelines are described as “voluntary” by the committees that write them, that is clearly not the case.  Although the zealots deny the existence of a chilling effect on prescribing, there are data that suggest that progressively fewer physicians are willing to prescribe opioids since these non-evidence-based guidelines have surfaced.  Despite being touted as voluntary, physicians fear regulatory sanction should they disobey them, and accordingly are taking opioids out of their treatment armamentaria. 

Are we suggesting that opioid therapy be considered the first-line treatment for chronic pain?  Certainly not.  Chronic opioid therapy should be considered only when other available treatments have proven ineffective. However, given the for-profit health insurance industry’s business ethic of cost-containment and profitability, insurance access to many treatments that may be superior to opioid therapy are out of reach for the vast majority of Americans. We also have to remember that 20% of Americans live in underserved areas in which more sophisticated and safer treatment options are completely inaccessible.

We are concerned about this ethical imbroglio, as it is extremely damaging to our patients who suffer from the disease of chronic pain.  To quote from our article, opioid prescribing guideline committees’ continued utilization of the antiquated and invalid concept of MEDD is “scientifically, ethically, and morally inexplicable.”

As a result of this highly unethical practice, “impressionist lawmakers and anti-opioid zealots are basing clinical policy decisions on flawed concepts that ultimately could adversely affect positive outcomes for legitimate pain patients.”

It’s difficult enough to suffer from chronic pain under the best circumstances.  What patients with pain and society in general certainly don’t need is a group of smug inexperienced pain policymakers, politicians, and managed care administrators impacting public policy by evoking pseudoscience. There is sufficient good science being published that demonstrates that their reliance upon the MEDD myth is highly disingenuous.

Michael E. Schatman, PhD, is a clinical psychologist who has spent the past 30 years working in multidisciplinary chronic pain management. Until recently, he served as the Executive Director of the Foundation for Ethics in Pain Care in Bellevue, WA.

Dr. Schatman is Editor-in-Chief of the Journal of Pain Research and Director of Research for the U.S. Pain Foundation.

Jeffrey Fudin, PharmD, is a Clinical Pharmacy Specialist and Director at the Pharmacy Pain Residency Programs at the Stratton Veterans Administration Medical Center in Albany, NY.  

Dr. Fudin is Diplomate to the American Academy of Pain Management and a Fellow of both the American College of Clinical Pharmacy and the American Society of Health-system Pharmacists. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Feds Quietly Release National Pain Strategy

By Pat Anson, Editor

The U.S. Department of Health and Human Services (HHS) on Friday quietly released the National Pain Strategy, a comprehensive and ambitious “roadmap” to improve the quality of pain care in the United States. The 83-page report was overshadowed by the opioid prescribing guidelines released by the Centers for Disease Control and Prevention just a few days earlier.

Development of the National Pain Strategy (NPS) began over five years ago after the Institute of Medicine released a report calling for a “cultural transformation” in pain care, prevention, research, and education. Although the NPS was being closely watched by researchers, academics, regulators and professional societies, many long-suffering pain patients will be surprised to hear the U.S. even has a national pain strategy.

The Department of Health and Human Services (HHS) did little to publicize the NPS, issuing a single news release that wasn’t even posted on its own website 24 hours later.  There was no press briefing for reporters to explain why the NPS was developed or what its objectives are.

The announcement wasn't even made by HHS Secretary Sylvia Mathews Burwell, but by a lower ranking aide.

“Chronic pain is a significant public health problem, affecting millions of Americans and incurring significant economic costs to our society,”  Karen DeSalvo, MD, acting assistant secretary for health at HHS, said in the news release. “This report identifies the key steps we can take to improve how we prevent, assess and treat pain in this country.”

The major goals of the NPS are:

• Develop new methods to prevent and manage pain.
• Improve pain education of physicians
• Develop “integrated, interdisciplinary, patient-centered” pain management teams
• Provide better insurance coverage of pain treatment options
• Reduce barriers to pain care, especially for stigmatized and underserved populations.
• Increase public awareness and patient knowledge of treatment options and risks

The 800-pound gorilla of pain management – opioid pain medicine – is only briefly mentioned in the NPS, and not in a positive way.

“Evidence suggests that wide variations in clinical practices, inadequate tailoring of pain therapies to individuals, and reliance on relatively ineffective and potentially high risk treatments such as inappropriate prescribing of opioid analgesics, or certain surgical interventions, not only contribute to poor quality care for people with pain, but also increase health care costs,” the report says.

“Treatments that are ineffective, whose risks exceed their benefits, or that may cause harm for certain subgroups need to be identified and their use curtailed or discontinued.”

“We need to ensure that people with pain get appropriate care and that means defining how we can best manage pain care in this country,” said Linda Porter, PhD, director of the National Institute of Health’s Office of Pain Policy and co-chair of an interagency committee that helped develop the report.

“To achieve the goals in this report, we will need everyone working together to create the cultural transformation in pain prevention, care and education that is desperately needed by the American public,” said Sean Mackey, MD, who heads the Division of Pain Medicine at Stanford University and is co-chair of the interagency committee.

Still unclear is how the NPS will ever be implemented, since it relies on major policy changes and coordinated action involving medical schools, healthcare providers, insurers, government agencies, Congress and the White House. No estimate is provided on how much it will cost or where funding will come from.

“The NPS is riddled with vague terms and objectives -- which render the whole effort too subject to interpretation,” says David Becker, a patient advocate and author of “Quotes on Pain.” “I find it fascinating that despite the outcry from individuals regarding very specific concerns and problems, they are intent on imposing population based public health solutions on individuals. They can’t see the trees for the forest. And their plan is to help some nameless faceless pain sufferers with a very homogenized approach.

“The whole report reminds me of a Seinfeld episode when he says his show is all about nothing. The NPS is about some vague objectives -- even though the underlying philosophy, politics, privileges -- are only too clear. I guess those privileged pain specialists just don’t wish to be pinned down too much about what their pig in the poke is all about.”

The NPS was quickly endorsed by the American Pain Society (APS), a professional group that focuses on pain research.

“The National Pain Strategy gives the nation a blueprint for aggressive action to expand access to effective pain care,” said APS President Gregory Terman, MD. “Pain is a serious and often neglected public health problem that is draining our health care resources. It is responsible for inestimable lost wages, impaired worker productivity, and extracts a tragic personal toll on patients and their families.”  

Terman and several other APS members were involved in drafting the National Pain Strategy, as well as the CDC’s opioid prescribing guidelines.

“We believe several high impact policy initiatives will emerge from implementation of the National Pain Strategy, especially in helping primary-care physicians, who see that vast majority of pain patients, become more knowledgeable about pain mechanisms, pain assessment, and safe use of analgesic medications,” Terman said.

Study Finds Errors in Drug Websites

By Pat Anson, Editor

Nearly six out of ten Americans adults have gone online for health information in the past year, usually to identify medical conditions and treatments, according to the Pew Research Center. But just how reliable is the information they found?

A research study led by drug maker Purdue Pharma found that several websites where physicians and consumers get information about medications contain misinformation that could potentially jeopardize patient safety.

Purdue and 10 other pharmaceutical companies evaluated five websites; Medscape, Lexicomp Online, Epocrates Online, Drugs.com and RxList, which are referred to as online drug information compendia (ODIC).  

The sites typically offer information on side effects, warnings, safety, and dosages for thousands of brand name and generic drugs. Medscape, for example,  calls itself “the most authoritative and accessible point-of-care medical reference available” on the Internet.

Although the content is “informative and easily accessible,” researchers say the websites contain misinformation that could lead to drugs being misused.

"This is an important study that highlights the need for HCPs (healthcare providers) and consumers to use multiple sources when seeking drug information, as there were a surprisingly large number of errors, including inaccuracies and outdated information, across various drug summaries in online drug information compendia," said lead author Amarita Randhawa, Senior Manager of Medical Services at Purdue Pharma, which makes OxyContin.

"As ODIC use expands, it is crucial to ensure drug summaries are up-to-date, accurate and complete. Purdue Pharma has implemented an ongoing compendia review process, which served as the model for this collaborative initiative." 

The 11 participating companies evaluated 270 drug summaries on the five websites and found a median average of 782 errors. Dosage and administration, patient education, and warnings and precautions were the categories with the greatest number of errors. Most of the errors invbolved information that was incomplete, inaccurate or omitted. 

The study, which is being published in the Annals of Pharmacotherapy, does not identify what drugs were evaluated, only that they are used to treat a variety of different conditions, including pain, diabetes, infectious diseases and cardiovascular problems.

“Boxed warning information for product B was incomplete because the warning regarding addiction, abuse, and misuse was not provided,” was one of the errors cited.

“The warning that product F may cause dizziness and somnolence and impair the ability to drive or operate machinery as described in the Medication Guide was missing,” was another error.

The two consumer oriented websites, Drugs.com and RxList, had fewer errors on average than the other three websites, which are mainly designed for physicians and healthcare providers.

“Although the intent of this study was not to compare one compendium with another, it should not be surprising that HCP-ODIC contained a greater number of errors compared with consumer-ODIC because of the detailed and indepth nature of HCP-focused drug summaries,” the researchers said.

The Consumer and Patient Health Information Section (CAPHIS) has compiled a list 100 health websites it considers trustworthy. The list can be accessed by clicking here.

The National Institutes of Health also has tips on finding reliable health information online.

Hospital Study Calls Chest Pain ‘Opportunity for Savings’

By Pat Anson, Editor

Reducing the cost of healthcare is a major goal for insurers, providers and patients, but some physicians say the state of Rhode Island is taking things too far by discouraging some patients from getting their pain treated.

The state’s Executive Office of Health and Human Services has issued a report that identifies $90 million in annual savings “by preventing non-emergency visits” to hospital emergency rooms. Chest pain is listed as “the greatest opportunity for savings” while back pain, abdominal pain and headache are considered “potentially preventable" reasons for emergency room care.

“While many people associate ‘chest pain’ with ‘heart attack’, a truly emergent and serious condition, the majority of those who present to the emergency room with chest pain and are not admitted to the hospital are not experiencing a heart attack,” the report says.

In Rhode Island, 46% of emergency room visits were considered potentially preventable for privately insured patients and 70% of the visits for Medicaid patients.

“A potentially preventable emergency room visit is when a patient goes to an emergency room for a health condition that could have been treated in a non-emergency setting or prevented by keeping them healthier earlier on. Treatment in an emergency room is generally more expensive than a primary care visit,” according to the report.

The average cost of an emergency room visit in Rhode Island varies considerably, from $368 for a Medicaid recipient to $1,154 for someone with private insurance.  

The American College of Emergency Physicians (ACEP) calls the report irresponsible and flawed, because it relies on data about patients’ final diagnoses, not their presenting symptoms. That analysis does not take into consideration the national "prudent layperson" standard in the Affordable Care Act (ACA), which says emergency visits must be covered by insurance companies based on the patients' symptoms, not their final diagnoses.

"It is very alarming that a report like this is being issued that directly undermines language in the ACA and patients' responsible use of the emergency department," said Jay Kaplan, MD, president of ACEP. "Patients never should be forced into the position of self-diagnosing their medical conditions out of fear of insurance not covering the visit. This applies 20/20 hindsight to possibly life-threatening conditions — such as chest pain — and it violates the national prudent layperson standard designed to protect patients' health plan coverage of emergency care."

Data in the Rhode Island report also does not correlate with the latest national data on emergency visits from the CDC, which found that 96 percent of emergency patients needed medical care within two hours.

"A report like this only serves to potentially scare patients away from the emergency department when they may need it most," said Christopher Zabbo, DO, president of ACEP's Rhode Island Chapter. "Both harmless and deadly conditions often have the same presentations. Asking patients to make that determination while at home, anxious, and with inadequate information, is a recipe for disaster."   

“I do all I can to stay away from our hospitals unless it is a planned surgery. I arrive with all my records, educated on my condition and find they (doctors) are immediately turned off due to my complications,” said Ellen Lenox Smith, a Rhode Island resident who suffers from Ehlers Danlos syndrome and is a columnist for Pain News Network. Ellen recently wrote about some of her bad hospital experiences and how she learned to avoid future ones. (see”How to Stop Hospital Horrors”).  

According to the CDC, stomach and abdominal pain were the number one reason for patients to visit an emergency room in 2011, followed by chest pain, fever, headache, cough and back pain.

Australians Lead Global Pain Survey

By Pat Anson, Editor

Australians have more aches and pains than anyone else in the world, but are least likely to complain about it.

Germans say their pain stings, the Chinese have a dull pain, in Japan it throbs, and the Poles say they’re numb from it.

And the Italians? Those Latin lovers are least likely to let pain interfere with their sex lives.

Those are some of the odder facts that emerged from a consumer research survey of 7,000 people in 14 countries conducted by GlaxcoSmithKline (GSK), a British pharmaceutical company.

The so-called Global Pain Index found that overall body pain – defined as aches in your muscles, tendons, ligaments and joints – truly knows no borders and is widespread throughout the world, but it affects people differently depending on where they live.

The survey found that Australians (97%) are most likely to report pain, followed by Russia (95%), China (94%), the UK (93%) and the United States (90%).

Swedes and Germans (88%) are least likely to feel pain.

The Chinese are most likely to complain about their pain (71%), followed by Mexicans (69%), Brazilians (57%) and Italians (55%). Only about a third of Australians complain about their pain.

People in the UK are most likely to see pain as just another part of life, even though it affects them negatively in a variety of ways. Over half (55%) say they cannot have sex because of body pain, two-thirds say it disrupts their social life, and 62% say pain has hurt their work performance.

Only about half (53%) the people in the UK know what is causing their pain.  

“Many people in the UK are taking the attitude that body pain is something you can ignore and hope it goes away, but this approach isn’t working. The findings of the GSK Global Pain Index have shown us that the UK is one of the countries where most people report feeling pain, but it also illustrates that we need a better understanding of our pain and how to treat it,” says Dr. Sarah Davis, a general practitioner in London.

“Pain is hurting every aspect of our lives in the UK, stopping people from enjoying time with friends and family, from enjoying the hobbies and sports they enjoy and hurting their prospects at work.”

The survey was conducted by the research firm Edelman Berland from November 2014 through January 2015 in Australia, Brazil, Canada, China, Germany, Italy, Japan, Mexico, Poland, Russia, Saudi Arabia, Sweden, UK and the United States.

Race and Economic Insecurity Play Key Roles in Pain

By Pat Anson, Editor

Two new studies are adding to the growing evidence that links pain with economic, social and racial differences in the United States.

Researchers at Indiana University-Purdue University say African-Americans use coping strategies that often make their pain worse; while researchers at the University of Virginia found that people who feel that their financial outlook is shaky experience more physical pain.

“The past decade has seen a rise in both economic insecurity and frequency of physical pain. The current research reveals a causal connection between these two growing and consequential social trends,” wrote lead author Eileen Chou of the University of Virginia in the journal Psychological Science.

Chou and her colleagues looked at six different studies and found that economic insecurity produces physical pain, reduces pain tolerance, and predicts consumption of over-the-counter pain relievers. The researchers believe economic insecurity also leads people to feel a lack of control in their lives, which activates psychological processes associated with anxiety, fear, and stress.

Data from a consumer panel of nearly 34,000 individuals revealed that households in which both adults were unemployed spent 20% more on over-the-counter pain relievers than households in which at least one adult was working.

Smaller studies also found that unemployment was correlated with reports of pain. And people who recalled periods of economic instability reported almost double the amount of physical pain than those who recalled economically stable periods.

“Overall, the findings show that it physically hurts to be economically insecure,” Chou said.

Financial stress and economic insecurity were also blamed in a recent landmark study by Princeton University researchers who found that nearly half a million middle aged white Americans died prematurely in the last 15 years. The rising death rate for whites was also attributed to drug and alcohol poisoning, suicide, chronic pain and disability.

Blacks and Whites Cope with Pain Differently

The researchers at Indiana University-Purdue University also used a meta-analysis (a study of studies) to reach their conclusion that black and white Americans cope with pain differently. The review of 19 studies, which included 2,719 black and 3,770 white adults, is the first to quantify the relationship between race and the use of pain-coping strategies.

"Coping" was broadly defined as the use of behavioral and cognitive techniques to manage stress.

Blacks were significantly more likely to use prayer and hoping as pain-coping strategies than whites, according to researchers. Blacks were also more likely than whites to think about their pain in a catastrophic manner.

"Our findings suggest that blacks frequently use coping strategies that are associated with worse pain and functioning," said Adam Hirsh, a clinical health psychologist. "They view themselves as helpless in the face of pain. They see the pain as magnified -- the worst pain ever. They ruminate, think about the pain all the time, and it occupies a lot of their mind space."

While that kind of coping might be considered a negative approach to pain, Hirsch says it also may have benefits.

“It may also be a potent communication strategy -- it tells others in a culture with a strong communal component that the person is really suffering and needs help. Thus, it may be helpful in some ways, such as eliciting support from other people, and unhelpful in other ways. In future studies, we will give this more nuanced investigation," said Hirsch, whose study is published in the Journal of Pain.

Ignoring pain rather than allowing it to interfere with the task at hand was the only coping strategy employed by whites more than blacks. Several studies reviewed by researchers found that ignoring strategies are associated with less pain, whereas praying, hoping and catastrophizing are associated with higher pain levels.

"How people think about their pain matters," said Hirsh. "For example, religion can be used as a passive coping strategy -- asking a higher authority to take the pain away -- or as an active coping strategy -- asking to be given strength to manage pain.”

Blacks reported higher levels of pain than whites for a number of conditions including arthritis, post-operative pain and lower-back pain. Blacks also experience greater pain in both clinical and experimental studies. Blacks reported less-effective pain care, are unable to return to work for a longer time due to pain, and have worse functional outcomes.

Hirsch says understanding how different racial groups cope with pain may improve pain care and support individually tailored treatment.