Vitamin D Supplements Could Ease Symptoms of IBS

By Pat Anson, Editor

A new study suggests that Vitamin D supplements may help ease stomach cramps, constipation and other painful symptoms of irritable bowel syndrome (IBS).

In a systematic review (a study of studies) involving hundreds of patients around the world, British researchers found that over half the patients with IBS had low levels of Vitamin D in their blood serum. Vitamin D supplements helped improve symptoms for some patients, although the findings were mixed.

"The available evidence suggests that low vitamin D status is common among the IBS population and merits assessment and rectification for general health reasons alone,” said Claire Williams of the University of Sheffield, lead author of the study published in the European Journal of Clinical Nutrition.

"An inverse correlation between serum vitamin D and IBS symptom severity is suggested and vitamin D interventions may benefit symptoms."

Williams and her colleagues cautioned that the evidence was not strong that supplements would help, and said larger studies were needed to build a case for Vitamin D as a treatment for IBS.

Britain’s National Health Service was also cautious about the findings.

“Although this possible link is worth investigating further, the evidence is currently very limited. The results seen in this study are an extremely mixed bag taken from studies of questionable quality," the NHS said in a review.

“The observational studies mainly just show that a number of these people with IBS also had a vitamin D deficiency. But you could select many other samples of people with IBS and find they have sufficient vitamin D levels, or other people who don't have IBS but who are vitamin D deficient.”

Both IBS and vitamin D deficiency are common in the western world. About 20% of adults in the UK are deficient in Vitamin D. Low levels of the “sunshine vitamin” have also been linked to fibromyalgia and multiple sclerosis. 

Most people get all the Vitamin D they need by being exposed to ultraviolet rays in sunlight. You can also get it by eating foods rich in Vitamin D, such as oily fish and eggs. Vitamin D has a wide range of positive health effects, such as strengthening bones and inhibiting the growth of some cancers.

Why Does Menopause Worsen Rheumatoid Arthritis?

By Pat Anson, Editor

A large new study is confirming what many women with rheumatoid arthritis (RA) already know – menopause and hormonal changes can significantly worsen their pain and other symptoms. But it's not clear why that happens.

Researchers at the University of Nebraska Medical Center enrolled over 8,000 women with RA – both young and old -- in their observational study. They found that post-menopausal women with RA had a significant increase in the level and rate of functional physical decline. Menopause was also associated with a worsening progression of the disease.

RA is a chronic and disabling autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and joint erosion. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

Previous studies have shown that women with RA experience changes in their disease during reproductive and hormonal changes. During pregnancy, women are less likely to develop RA, yet the disease is more likely to progress and flare during the post-partum period. Similarly, women who experience early menopause are more likely to develop RA compared to those who experience normal or late menopause.

Hormone levels of estrogen increase during pregnancy and decline during menopause – but the association with RA is not fully understood.

"Further study is needed as to why women with rheumatoid arthritis are suffering a greater decline in function after menopause," said the study's lead author, Elizabeth Mollard, PhD, an assistant professor in the College of Nursing at the University of Nebraska Medical Center.

"Not only is this decline causing suffering for women, it is costly to both individuals and the healthcare system as a whole. Research is specifically needed on the mechanism connecting these variables with the eventual goal of identifying interventions that can maintain or improve function in postmenopausal women with rheumatoid arthritis."

The study is published in the journal Rheumatology.

RA affects about 1.3 million Americans and about one percent of the global population. Until the late 1990s, one in three RA patients were permanently disabled within five years of disease onset.

Although there are still no cures for RA, in recent years there has been significant improvement in treatment, with disease control now possible for many patients who receive biologic drugs. Those treatments are expensive, with some biologic therapies costing $25,000 a year.

Losing Weight Helps Lower Pain Levels

By Pat Anson, Editor

Those of us who made a New Year’s resolution to lose weight have a little more incentive to keep our pledge – thanks to new research showing that even a small weight loss reduces overall body pain, as well as fatigue and depression.

The University of Michigan study, published in The Journal of Pain, involved 123 obese participants who were put on a low-calorie liquid diet for 12 weeks and asked to gradually increase their physical activity. The goal was to lose at least 10 percent of their body weight.

“It’s been known for some time that people who are obese tend to have higher levels of pain, generally speaking,” says Andrew Schrepf, PhD, a research investigator at Michigan Medicine’s Chronic Pain and Fatigue Research Center. “But the assumption has always been the pain is going to be in the knees, hips and lower back — parts of the body that are weight-bearing.”

Schrepf and his colleagues found that losing weight not only lowered pain levels in the knees and hips, but in unexpected areas such as the abdomen, arm, chest and jaw. Study participants who could reach the goal of losing 10% of their weight also reported better mental health, improved cognition and more energy. Men in particular showed improvements in their energy levels.

The results are significant because previous research hasn’t shown how weight loss affects widespread pain throughout the body.

“We know when people lose a lot of weight they tend to feel better,” Schrepf says. “But astonishingly, no one ever looked at where in the body the pain gets better.”

Researchers surveyed participants about their pain and other symptoms before and after the 12 week diet, using fibromyalgia assessment criteria to make their determinations. Participants were also evaluated and counseled by physicians and dietitians who specialize in endocrinology and obesity medicine.

Of the 123 participants, 99 were able to lose 10 percent or more of their body weight.

“The focus in the program is on calorie restriction and long-term weight loss, although all patients are encouraged to get more physically active for the other health benefits that exercise provides,” says Amy Rothberg, MD, an associate professor of endocrinology nutritional sciences at U-M. “The truth is people are, paradoxically, far more energetic on a low-energy diet and find after they begin losing weight that they can do more and are more physically active.”

Participants who met the weight loss goal reported widespread improvement in pain compared to those who did not. Their blood samples also showed a spike in anti-inflammatory molecules — a key weapon in fighting many types of pain. Researchers say the widespread improvement in body pain suggests that joints aren’t the only conduit of chronic pain.

“What we think that means is this process of losing weight may be affecting the central mechanisms of pain control related to the brain and spinal cord,” said Schrepf.

In future research, the team hopes to better understand why losing 10% of body weight was the dividing line for reduced pain.

“Some of your earliest weight loss isn’t all fat; it could be water,” Schrepf says. “Somewhere around 10 percent we’re reaching some kind of critical mass, but it’s hard to know exactly what that means.”

The Difference Between Intractable and Chronic Pain

By Forest Tennant, MD, DrPH

The current attempts by a number of parties to castigate and humiliate pain patients and their medical practitioners is not just pathetic and mostly false, it is dangerous to the fate and life of many intractable pain (IP) patients.  If it wasn’t so serious, some of the claims, biases and beliefs would make good comedy.

First and foremost there has been no discussion about the difference between intractable pain and chronic pain.  There really is no bigger issue. 

The proper identification and treatment of the IP patient is not only essential for the health and well-being of the IP patient, it is a major key to the prevention of overdoses and diversion of abusable drugs.  IP patients must have special care and monitoring.  

The basic definition of IP is a “moderate to severe, constant pain that has no known cure and requires daily medical treatment.” 

Chronic pain, on the other hand is a “mild to moderate, intermittent, recurring pain that does not require daily medical treatment.” While there are millions of persons with chronic pain, only about 10% are intractable.

The cause of “intractability” is two-fold:

1. The initial injury or disease which initiated IP was severe enough to cause a pathologic transformation of the microglial cells in the spinal cord and/or brain. It is this transformation that produces neuroinflammation and the constancy of the pain. This process is known as “centralization” or “central sensitivity.”

2. To have enough injury to cause “centralization” one must have a most serious disease or condition of which the most common are: adhesive arachnoiditis, traumatic brain injury, reflex sympathetic dystrophy, post-viral encephalopathy, or a genetic disease such as Ehlers-Danlos Syndrome, porphyria, or sickle cell disease.

Medical practitioners must have minimally-restricted prescribing authority and autonomy to adequately treat IP.  For example, the proper treatment of IP not only requires analgesics, opioids and non-opioid, but specific anti-inflammatory, hormonal, and corticosteroid agents that will cross the blood brain barrier and control inflamed and pathologic microglial cells.  Treatment of IP has to be individually tailored and may require non-standard, off-label, or an unusual treatment regimen.  

Make no mistake about it.  The new treatment approach to IP is quite effective in reducing pain, controlling neuroinflammation, and allowing patients to biologically function well enough to have a good quality of life.  Also be advised that the new IP approach is not just reducing pain but treating the underlying cause of pain.  Consequently, a lot of expensive procedures, therapies, and opioids are no longer needed. 

As long as I am practicing I will continue to push forward this new approach.

Dr. Tennant specializes in the research and treatment of intractable pain at the Veract Intractable Pain Clinic in West Covina, California, which remains in operation after recently being raided by DEA agents. Many of Dr. Tennant's patients travel from out-of-state because they are unable to find effective treatment elsewhere.

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

Fibromyalgia Linked to Overactive Brain Networks

By Pat Anson, Editor

Many fibromyalgia sufferers have been told that the pain is “all in their head.” New research indicates there may be some truth to that, and that overactive brain networks could play a role in the hypersensitivity of fibromyalgia patients.

Fibromyalgia is a poorly understood disorder characterized by deep tissue pain, fatigue, headaches, mood swings and insomnia. There is no known cause and successful treatments have been elusive.

In a lengthy study published in the journal Scientific Reports, an international team of researchers at the University of Michigan and in South Korea report that patients with fibromyalgia have brain networks primed for rapid responses to minor changes. This abnormal hypersensitivity is known as called explosive synchronization (ES).

"For the first time, this research shows that the hypersensitivity experienced by chronic pain patients may result from hypersensitive brain networks," says co-senior author Richard Harris, PhD, an associate professor of anesthesiology at Michigan Medicine’s Chronic Pain and Fatigue Research Center.

In ES, a small stimulus can lead to a dramatic synchronized reaction throughout the network, as can happen when a power outage triggers a major grid failure or blackout. Until recently, this phenomenon was studied in physics rather than medicine. Researchers say it's a promising avenue to explore in the quest to determine how a person develops fibromyalgia.

"As opposed to the normal process of gradually linking up different centers in the brain after a stimulus, chronic pain patients have conditions that predispose them to linking up in an abrupt, explosive manner," says first author UnCheol Lee, PhD., a physicist and assistant professor of anesthesiology at Michigan Medicine.

The researchers tested their theory by conducting electroencephalogram (EEG) tests on the brains of 10 female patients with fibromyalgia. Baseline EEG results showed the patients had hypersensitive brain networks, and that there was a strong correlation between the degree of ES conditions and the self-reported intensity of their pain during EEG testing.

Lee's research team and collaborators in South Korea then used computer models of brain activity to compare the stimulus responses of the fibromyalgia patients to those of healthy ones. As expected, the fibromyalgia model was more sensitive to electrical stimulation.

"We again see the chronic pain brain is electrically unstable and sensitive," Harris says.

Harris says this type of modeling could help guide future treatments for fibromyalgia. Since ES can be modeled outside of the brain in computers, researchers can test for influential regions that transform a hypersensitive network into a more stable one. These regions could then be targeted in living humans using noninvasive brain modulation therapies such as transcranial magnetic stimulation, which is currently used to treat fibromyalgia and depression.

“We expect that our study may ultimately suggest new approaches for analgesic treatments. ES provides a theoretical framework and quantitative approach to test interventions that shift a hypersensitive brain network to a more normal brain network,” researchers reported. 

“It may be possible to convert an ES network to a non-ES network just by modulating one or two hub nodes. Indeed, transcranial magnetic stimulation and/or transcranial direct current stimulation may be improved by ‘targeting’ these sensitive hub nodes. The application of deep brain stimulation to critical nodes that could modify ES conditions is another therapeutic possibility that could be explored.”

The research was funded by the Cerephex Corporation, James S. McDonnell Foundation, and the National Institutes of Health

Scientists Building a Safer Opioid

By Pat Anson, Editor

Researchers at the University of North Carolina believe they’ve found a way to create a new type of opioid medication that relieves pain without risky side effects.

Currently, opioid painkillers bind to several opioid receptors on the surface of brain cells, triggering a wide range of side effects -- from nausea, numbness and constipation to anxiety, addiction and potentially fatal respiratory depression.

The UNC researchers report in the journal Cell that they have created a new drug compound that only activates the kappa opioid receptor – the brain receptor that is the key to pain relief.

"To create better opioids, we need to know the structure of their receptors," said senior author Bryan Roth, MD, a professor in the Department of Pharmacology at UNC School of Medicine.

"Until recently, this was impossible. But now we know the structure of the activated kappa opioid receptor. And we showed we can actually use the structure to make a drug-like compound with better properties than current opioids."

The compound was created in cell cultures in Roth's lab, and still needs to be tested in animal models. But knowing the detailed structure of the kappa opioid receptor (KOR) has opened the door to developing other drug-like compounds that are highly selective for specific opioid receptors.

KAPPA OPIOID RECEPTOR (unc IMAGE)

"Tens of thousands people who take opioids die every year, and so we need safer and more effective drugs for treating pain and related conditions," Roth said in a news release. "One of the big ideas is to target KORs because the few drugs that bind to it don't lead to addiction or cause death due to overdose. Those side effects are mainly related to actions at the mu opioid receptor."

Drugs that bind to KORs can still have side effects, such as hallucinations and dysphoria - a state of unease or dissatisfaction with life related to anxiety and depression. That is why scientists say it’s important to know how this receptor is activated – so they can figure out a way to bind a compound to KORs so that it only relieves pain.

"Now we have a much better understanding of the direction we have to explore in order to create a selective drug to activate only kappa opioid receptors," said corresponding author Daniel Wacker, PhD, UNC School of Medicine.

The UNC research was funded by the National Institutes of Health, the Mayday Fund, and the Peter F. McManus Trust.

Genetics Play Significant Role in Post-Surgical Pain

By Pat Anson, Editor

An important new study has confirmed that a patient’s genes really do play a role in determining whether they develop chronic pain after surgery.

Researchers in China collected blood samples from 1,152 surgical patients to look for genetic variations in 54 "pain-related" genes which have been associated with pain sensation. Patients were then contacted a year later to see if they had chronic post-surgical pain.

A surprising number – one out of five patients – still experienced pain at the wound site, and 33 percent of them said their pain was severe.  Patients with pain also reported problems with their overall health, as well as daily activities such as mood, walking, relations with others, sleep, and quality of life.

Aside from genetic factors, the study also found patients younger than 65, males, and those with a prior history of chronic pain were at increased risk. The study is published online in the journal Anesthesiology.

"Our study not only shows there are common genetic variations among people that may help to identify whether they are at high-risk for developing chronic pain after surgery, but it also helps explain why only a fraction of patients ever even experience persistent pain," said lead researcher Matthew T.V. Chan, MD, at the Chinese University of Hong Kong.

"Until now, the genetic variations associated with chronic post-surgical pain have not been well identified."

One genetic variation in particular - a gene found in the nervous-system called brain-derived neurotrophic factor (BDNF) - was found to be most frequently associated with chronic post-surgical pain. Researchers confirmed the finding in a study on laboratory mice.

The researchers also found that genetic variations account for a higher percentage of chronic post-surgical pain (between 7 percent and 12 percent) than other risk factors such as age, sex, smoking history or anesthesia technique (between 3 percent and 6 percent).

Chronic post-surgical pain is one of the most common and serious complications after surgery. Previous studies have found that chronic pain was common after abdominal hysterectomies (25.1%) and heart or lung surgery (37.6%).

“Considering that more than 230 million surgeries are performed each year worldwide, the data would imply that millions of patients will continue to suffer wound pain, months to years after their surgery,” researchers said.

The study comes at a time when many U.S. states have adopted or are enacting laws that would limit the supply of opioid medication to just a few days for acute short-term pain. Minnesota, for example, is close to adopting strict guidelines that would limit the dose and supply of opioids to three days for acute pain and seven days after a major surgery.

Painkiller Study Conducted at Poorly Rated Hospital

By Pat Anson, Editor

Over-the-counter pain relievers are just as effective as opioid medication in treating short-term acute pain in a hospital emergency room, according to a widely touted study published in the Journal of the American Medical Association (JAMA).

The study was relatively small – only 416 patients participated – and it was conducted at a New York City hospital with a poor history of pain care. Still, it's getting a lot of media coverage. “Milder pill may be best for pain” is the front page headline in the Los Angeles Times. “Drugstore pain pills as effective as opioids” said STAT News. “Opioids Not the Only Answer for Pain Relief” reported HealthDay.  

Researchers said patients with moderate to severe acute pain in their arms or legs got just as much pain relief after being given a combination of acetaminophen and ibuprofen than those who took hydrocodone, oxycodone or codeine. The study only measured pain relief for two hours.

Patients with sickle cell disease, fibromyalgia, neuropathy or any type of pain that lasted more than seven days were excluded from the study because researchers only wanted to focus on short term pain.

"Although this study focused on treatment while in the emergency department, if we can successfully treat acute extremity pain with a non-opioid combination painkiller in there, then we might be able to send these patients home without an opioid prescription," said lead author Andrew Chang, MD, a professor of emergency medicine at Albany Medical Center.

"We know that some patients who are given an opioid prescription will become addicted, so if we can decrease the number of people being sent home with an opioid prescription, then we can prevent people from becoming addicted in the first place."

What Chang, JAMA and the news reports all fail to mention is that the study was conducted at one of the worst hospitals in the nation. In an annual survey of Medicare patients, Montefiore Medical Center in New York City was given only one star (out of five possible), placing it in the bottom 2.44% of hospitals nationwide.

Montefiore was rated poorly on a variety of quality measures, including pain care. Only 64 percent of the patients treated there said their pain was “always” well controlled, compared to the national average of 71 percent.

‘Worst Hospital in the Entire City’

Many of the online reviews of Montefiore’s emergency room are scathing.

“Please do not come to the ER unless you want to die or are used to unsympathetic health professionals,” warned Amanda G. on Yelp.  “I have severe abdominal pain and I'm walking home in tears right now. I came in told the nurse there my symptoms and she couldn't have made it clearer that she couldn't care less.”

“This has to be the worst hospital in the entire city. The nurses in the ER are rude and don't care about your well being. The ER is filthy. People stacked on top of each other,” wrote Robert in a Google review.

MONTEFIORE MEDICAL CENTER PHOTO

“The emergency room sucks. The doctors sit around on the computers gossiping. I even overheard a few doctors saying ‘why aren’t we picking up patients?’ Meanwhile there’s a room full of patients not being taken care of. There’s a patient screaming for help and no one hears him. All the staff members just walk by him,” wrote Zoe D. on Yelp.

“Somebody told me this place was the equivalent of going to a hospital in Manhattan. They lied! I went to the emergency room today for chest pains, I ended up sitting there for four hours never to be seen by a doctor. I ended up walking out and leaving still with my chest pains,” said Phonz R. on Yelp.

“Their ER department is horrible. I went to the ER with my mom via ambulance, we got there (a little) before 1pm. Fast forward 1:58 in the morning she still wasn't put in a room,” wrote J.L. Eaddy on Google. “This was the absolute worst ER I've ever encountered. And I NEVER want to come back again. I wish I had the option to give it negative stars.”

Unfortunately, complaints such as these are not unusual in busy, urban teaching hospitals like Montefiore.  And not all the reviews are poor. U.S. News and World Report gave high rankings to Montefiore in a number of areas, although it didn’t specifically rank its emergency department. Montefiore was recently given a lukewarm “C” rating by the Leapfrog group, a non-profit that grades hospitals on quality and safety.  

Many pain patients have poor experiences in hospitals. In a survey of nearly 1,300 patients by PNN and the International Pain Foundation, over half rated the quality of their pain care in hospitals as either poor or very poor. About two-thirds of the patients said non-opioid pain medications were ineffective.

Nursing Textbook Slammed for Racist Content on Pain

By Pat Anson, Editor

Blacks believe suffering and pain are inevitable. Hispanics believe pain is a form of punishment. Muslims consider pain a test of faith. Jews are vocal and demanding about pain care.

Those are some of the startling claims being made in "Nursing: A Concept-Based Approach to Learning," a nursing textbook that has a section that looks at ethnic and cultural differences in how people respond to pain.

The book advises nursing students that a patient’s culture and religion play a “critical role” in how a patient responds to acute or chronic pain, and that “nurses must approach each client with cultural competence.”

Fair enough. But then the book makes sweeping generalizations about various ethnic groups that some consider offensive and racist.

“Clients from Asian cultures often value stoicism as a response to pain. A client who complains openly about pain is thought to have poor social skills,” the book declares.

“Native Americans may prefer to receive medications that have been blessed by a tribal shaman…. They may pick a sacred number when asked to rate pain on a numerical scale.”

The textbook has been used by nursing students for years, but the section on diversity and culture drew little attention until a page from the book started circulating on social media this week.

“This is an excellent example of how not to be even remotely culturally sensitive. These assumptions are not evidence-based, they encourage nurses to ignore what a patient is actually saying,” said Onyx Moore, who posted the page on Facebook. “If a patient tells you their pain level, believe them -- because *they* are the expert on their body."

“I'm so disgusted. In 2017 how is this being published?” asked one poster. “Why isn't the protocol basic compassion instead of that ignorant nonsense?”

"I’ve seen so many examples like this in my nursing textbooks. It’s infuriating," wrote another Facebook poster.

“This is horrifyingly wrong,” said another.

In response to the uproar on social media, the book’s publisher apologized and said it would drop the offending section from the textbook.

“While differences in cultural attitudes towards pain are an important topic in medical programs, we presented this information in an inappropriate manner. We apologize for the offense this has caused and we have removed the material in question from current versions of the book, electronic versions of the book and future editions of this text,” Scott Overland, Pearson Publishing’s communications director told Mic.com.

“In addition, we now are actively reviewing all of our nursing curriculum products to identify and remove any remaining instances of this inappropriate content that might appear in other titles.”

Now in its second edition, “Nursing: A Concept-Based Approach to Learning” is still available for sale on Amazon, where a new hardcover can be bought for $235. First published in 2014, many of the early reviews of the book are positive, with some nursing students saying it was “indispensable” and a “life safer.”

The more recent reviews -- apparently in response to the uproar on social media -- are scathing.

“This book should cease to be printed. The fact that this is taught in schools makes me quite literally sick,” one reviewer said.

“This book is racist and if you apply it's concepts you will hurt your patients and possibly get in some uncomfortable situations or even litigation,” said another.

“If this kind of racist dreck can pass unnoticed by the authors AND editors of this book, it cannot be trusted. And they cannot be trusted. Unbelievable,” wrote another reviewer.

Pearson is the world’s biggest publisher of educational textbooks. Today the company put a video on its YouTube page in which Tom Bozik, president of Pearson’s global product development, made another apology and said the book doesn't represent the company's values.

CDC Releases More Faulty Research About Opioids

By Pat Anson, Editor

A new study by researchers at the Centers for Disease Control and Prevention estimates that opioid overdoses have shaved two and a half months off the average life span of Americans – a somewhat misleading claim because the study does not distinguish between legally obtained prescription opioids and illegal opioids like heroin and illicit fentanyl.

The research letter, published in the medical journal JAMA, looked at the leading causes of death in the U.S. from 2000 to 2015. Overall life expectancy rose during that period, from 76.8 years in 2000 to 78.8 years in 2015, largely due a decline in deaths from heart disease, cancer, stroke, diabetes and other chronic health conditions.

But deaths due to Alzheimer’s disease, suicide, liver disease, drug poisoning and opioid overdoses rose, collectively causing a loss of 0.33 years in life expectancy – most of it due to opioids.

“This loss, mostly related to opioids, was similar in magnitude to losses from all the leading causes of death with increasing death rates,” wrote lead author Deborah Dowell, MD, of the CDC’s National Center for Injury Prevention and Control.

“U.S. life expectancy decreased from 2014 to 2015 and is now lower than in most high-income countries, with this gap projected to increase. These findings suggest that preventing opioid related poisoning deaths will be important to achieving more robust increases in life expectancy once again.”

Dowell was also one of the lead authors of the CDC’s 2016 opioid prescribing guidelines, which discourage physicians from prescribing opioids for chronic pain. She and her two co-authors in the JAMA study --  both of them CDC statisticians -- do not explain why they failed to distinguish between black market opioids and legal prescription opioids, a dubious use of statistics akin to lumping arsonists in the same category as smokers or Boy Scouts learning to build campfires.  

They also fail to even mention the scourge of heroin and illicit fentanyl sweeping the country, which now accounts for the majority of opioid overdoses in several states.  

But Dowell and her co-authors don't stop there. The say the actual number of deaths caused by opioids is “likely an underestimate” because information on death certificates is often incomplete and fails to note the specific drug involved in as many as 25% of overdose deaths. This is another disingenuous claim, because it fails to explain why the data on the other 75% of overdoses is faulty too. 

Epidemic of Despair

Other researchers have also tried to explain the disturbing decline in American life expectancy – which began over adecade ago for middle-aged white Americans. Princeton researchers Anne Case and Angus Deaton were the first to document that trend,  when they estimated that nearly half a million white Americans may have died early because of depression, chronic pain, suicide, alcohol and drug abuse, and other health problems – an epidemic of despair linked to unemployment, poor finances, lack of education, divorce and loss of social connections.

The evidence was right there for Deborah Dowell and her co-authors had they looked for it. The JAMA study found that over 44,000 Americans committed suicide in 2015, a 66% increase from 2000, and over 40,000 died from chronic liver disease or cirrhosis, another 66% increase. Opioid overdoses during that same period rose to 33,000 deaths. 

Which is the bigger epidemic?

As PNN has reported, the CDC ignored early warnings from its own consultant that the agency’s opioid guidelines were being viewed as “strict law rather than a recommendation,” causing many doctors to stop prescribing opioid pain medication. Chronic pain patients also feel “slighted and shamed” by the guidelines, and are increasingly suicidal or turning to street drugs. We’ve also reported that the CDC has apparently done nothing to study the harms or even the possible benefits the guidelines have caused since they were released 18 months ago.

Instead of going back in time and selectively mining databases to fit preconceived notions about opioids, perhaps it is time for the CDC to take a giant step forward and see what its opioid guidelines have actually done.

Vitamin D Levels May Help Predict Risk of MS

By Pat Anson, Editor

Vitamin D levels in the blood may help predict whether a person is at risk of developing multiple sclerosis, according to a large new study published online in the journal Neurology.

The findings provide the best evidence to date that low levels of Vitamin D may be a contributing factor to multiple sclerosis (MS), a chronic and incurable disease which attacks the central nervous system.

“There have only been a few small studies suggesting that levels of vitamin D in the blood can predict risk,” said study author Kassandra Munger, ScD, of the Harvard T.H. Chan School of Public Health in Boston. “Our study, involving a large number of women, suggests that correcting vitamin D deficiency in young and middle-age women may reduce their future risk of MS.”

Munger and her colleagues analyzed a database derived from blood samples taken during prenatal testing of over 800,000 Finnish women. Using hospital and prescription records, they were able to identify 1,092 of those women who were later diagnosed with MS. They were compared to a control group of 2,123 women who did not develop the disease.

Of the women who developed MS, 58% had deficient blood levels of vitamin D, compared to 52% of the women who did not develop the disease.

Deficient blood levels of vitamin D were defined as fewer than 30 nanomoles per liter (nmol/L). Insufficient levels were 30 to 49 nmol/L and adequate levels were 50 nmol/L or higher.

Researchers found that with each 50 nmol/L increase in vitamin D in the blood, the risk of developing MS later in life decreased by 39 percent. In addition, women who had deficient levels had a 43% higher risk of developing MS than women who had adequate levels.

“More research is needed on the optimal dose of vitamin D for reducing risk of MS,” said Munger. “But striving to achieve vitamin D sufficiency over the course of a person’s life will likely have multiple health benefits.

"Our results further support and extend those of previous prospective studies of (Vitamin D) levels in
young adults and risk of MS, and suggests that many individuals are exposed to an increased MS risk that
could be reduced by broad population-based programs to prevent vitamin D deficiency."

Participants in the study were primarily white women, so the findings may not be the same for other racial groups or men. Also, while the blood samples were taken an average of nine years before MS diagnosis, it is possible some women may have already had MS when their blood was drawn and were not yet showing symptoms of the disease.

MS causes numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain. Symptoms begin with a series of irregular relapses, and after about 20 years MS worsens into a secondary progressive stage of the disease.

Low blood levels of vitamin D – known as the “sunshine vitamin”-- have previously been linked to an increased risk of developing MS. Danish researchers found that MS patients who spent time in the sun every day during the summer as teenagers developed the disease later in life than those who spent their summers indoors.

Ultraviolet rays in sunlight are a principal source of Vitamin D, which has a wide range of positive health effects, such as strengthening bones and inhibiting the growth of some cancers.

Do Half of Americans Really ‘Misuse’ Drugs?

By Pat Anson, Editor

One of the nation’s largest drug testing companies has released a study claiming that over half of Americans who are prescribed medication show signs of drug misuse, including potentially dangerous drug combinations.

In 2016, Quest Diagnostics found that 52% of patient test results were “inconsistent” with their prescribed medications. That was an improvement over the rate found in 2011, when 63% of samples were inconsistent.

The Quest report, titled "Prescription Drug Misuse in America: Diagnostic Insights in the Growing Drug Epidemic," is based on an analysis of 3.4 million laboratory tests performed between 2011 and 2016.

Many of the specimen samples came from patients being treated in pain management and addiction treatment clinics, which are not representative of the population as a whole.

Like previous studies of its kind, Quest broadly defines what constitutes drug “misuse” – a misleading term many people associate with abuse, addiction and diversion. Nearly a quarter of the patients (23%) with inconsistent results had no drugs detected in their system, which simply means they were not taking medications as directed.

The other 77% tested positive for illegal drugs or for a medication they were not prescribed.

"Over the past several years, federal and state government, clinician organizations, public health advocates and providers have all launched campaigns to educate the public about the perils of prescription drug misuse, which hypothetically should have yielded a significant rate of improvement. Yet our study shows that every other American tested for possible inappropriate use of opioids and other prescription drugs is potentially at risk," said F. Leland McClure, PhD, director of medical affairs at Quest Diagnostics.

"This finding is rather shocking, and speaks to the challenges of combating the nation's drug misuse epidemic."

Are the results really all that shocking? Or were they ginned up to hype the so-called epidemic? Consider some of the reasons a patient may not take a drug or have an inconsistent test result:

• Patient didn't like side effects from a medication
• Pain or other symptoms have subsided, so medication is not needed
• Patient skipped a dose
• Patient cannot afford a medication
• Patient can’t find a pharmacy willing to fill their prescription
• Patient may be a “rapid metabolizer” of a medication
• Physician may not be aware another doctor prescribed a drug
• Inaccurate drug test

The latter is a very real problem in the drug testing industry. As PNN has reported, “point-of-care” urine tests widely used by pain management and addiction treatment doctors to screen patients for illicit drug use are wrong about half the time, often giving false positive or false negative results for drugs like marijuana, oxycodone and methadone. 

The Quest study identified some disturbing and encouraging trends in drug use.

It wasn't opioids but benzodiazepines – a class of anti-anxiety medication that includes Xanax – that were most likely to be misused by adults over the age of 25.  Marijuana was most likely to be misused by people aged 18 to 24.   Opioids were second in both age groups.

Quest researchers found a striking decline in drug misuse among adolescents 10 to 17 years of age. The inconsistency rate for adolescents dropped from a whopping 70% in 2011 to 29% in 2016. Amphetamines and attention deficit disorder drugs were most likely to be abused by adolescents.

Among nearly 34,000 patient samples tested for opioids, alcohol and benzodiazepines, more than 20% were positive for opioids and benzodiazepines, 10% were positive for alcohol and opioids, and 3% were positive for all three.  Any combination of these drugs raises the risk of respiratory depression and overdose.

Misuse rates were higher for men and women of reproductive age (58%) than in the general study population (52%). The findings are significant because opioid and benzodiazepine use may decrease male fertility and, if taken during pregnancy, increase the risk of birth defects and other health concerns.

Quest is one of several drug testing laboratories that have been fined millions of dollars for paying kickbacks to physicians and patients for medically unnecessary tests.  Recent guidelines adopted by the American Society of Addiction Medicine warn doctors about ordering expensive drug tests that have led to “unethical and/or fraudulent activities.”

Researchers Question Value of Brain Imaging

By Pat Anson, Editor

An international team of researchers is recommending against the use of brain imaging as a diagnostic test for chronic pain, saying the tests are “inappropriate and unethical.”

"It's not possible at this point in time to say with any degree of certainty that a person does or does not have chronic pain based on brain imaging," said Karen Davis, PhD, senior scientist at the Krembil Research Institute and a professor at the University of Toronto.

"The only way to truly know if someone is in pain is if they tell you because pain is subjective and it is a complex experience. No brain scan can do that."

In recent years, technological advances in brain imaging have led to an increased use of functional magnetic resonance imaging (fMRI) to search for brain-based biomarkers for chronic pain.

Demand for brain imaging is also growing for legal purposes, including the development of a potential “lie detector” test for chronic pain.

"Use of such tools would be inappropriate and unethical," said Davis. "This technology is not foolproof. There are vast issues of variability between people and even within a person at different times. As a result, brain imaging must not be used as a lie detector for chronic pain."

Davis and her colleagues say brain-based biomarkers should only be used to supplement -- not replace -- a patient’s own reports of pain, even if testing is improved and valid protocols developed. Their recommendations were published in the journal Nature Review: Neurology.

"We are working towards biomarkers for chronic pain, but the goal is not as a lie detector test but rather to help provide personalized pain treatment options for patients," Davis. “People outside of the field of imaging might be disappointed, but the fact of the matter is the technology cannot be used to support or dispute a claim of chronic pain."

According to a 2015 study at the University of Michigan, one in eight visits to a doctor for a headache or migraine end up with the patient going for a brain scan. Often a doctor will order an fMRI to ease a patient’s fear that they may have a brain tumor or some other serious health problem. Doctors may also order a test to protect themselves in case of a lawsuit. About 1 to 3 percent of brain scans of patients with repeated headaches identify a cancerous growth or aneurysm.

University of Michigan researcher Brian Callaghan, MD, identified 74 neurological tests and procedures that are often unnecessary. Many involve the use of imaging.

“The two biggest areas that might be done more than they should are imaging for low back pain and imaging for headaches,” Callaghan said. “It’s a big problem and it costs a lot of money – we’re talking a billion dollars a year on just headache imaging.”

Other researchers believe brain imaging can be used as a valuable diagnostic tool. In a small study at the University of Colorado Boulder, researchers used fMRIs to discover a “brain signature” that identifies fibromyalgia with 93 percent accuracy. They found three neurological patterns in the brain that correlate with the pain hypersensitivity typically experienced with fibromyalgia.

How Fish Got Hooked on Hydrocodone

By Pat Anson, Editor

We hear it all the time from PNN readers. They don’t trust academic research about opioids and addiction, and feel much of it is biased or just plain fishy.

You can certainly say the latter about a new study by researchers at the University of Utah.

They devised a system that allows zebrafish, a small tropical fish popular in home aquariums, to self-administer doses of the painkiller hydrocodone. In less than a week, researchers say the fish were hooked on hydrocodone and showed signs of drug-seeking behavior and withdrawal.

"We didn't know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug," said Randall Peterson, PhD, a professor of Pharmacology and Toxicology, and senior author of the study published in the journal Behavioral Brain Research.

"What is exciting about this work is that we see many of the hallmarks of addiction in zebrafish. This could be a useful and powerful model."

How is this useful and how does it relate to people?

Zebrafish have more in common with people than you might think. They have 70 percent of the genes that humans have, including similar biological pathways that can lead to addiction. Like people, zebrafish have a μ-opioid receptor and two neurotransmitters, dopamine and glutamate, that trigger the natural reward system in the brain.

"Drugs of abuse target the pathways of the pleasure centers very effectively," said first author Gabriel Bossé, PhD. "These pathways are conserved in zebrafish, and the fish can experience some of the same signs of addiction and withdrawal as people."

Bossé and Peterson tested their system in a tank with a food dispenser equipped with a motion detector that the fish could trigger by swimming nearby. It didn’t take long for the zebrafish to learn how to get food.

Then the researchers removed the food dispenser and replaced it with one that injected small doses of hydrocodone into the water when a fish swam nearby. A continuous flow of water flushed the tank, which forced the fish to trigger the dispenser to receive another dose of hydrocodone.

Over the course of five days, the fish learned how to self-administer the drug. You can watch a demonstration below:

"The fish needed to perform an action to get the drug rather than receiving it passively," said Bossé. "Drug-seeking has been modeled before in rodents and primates, but having a model to study this in zebrafish could move the [study of addiction] forward."

The drug-seeking behavior increased when the zebrafish were forced to receive the opioid in progressively shallower water, a stressful environment that unconditioned fish would normally avoid.

"This was important, because we forced the fish to do more work to receive the drug, and they were more than willing to do more work," said Peterson.

The researchers took their experiment a step further by exposing the conditioned fish to naloxone, a drug used to treat overdoses that blocks opioid receptors. Sure enough, naloxone appeared to reduce the fish’s drug-seeking behavior.

The researchers believe their zebrafish model can lead to new drug therapies, because it can be used to rapidly test thousands of different chemical compounds. They also believe the genetic make-up of zebrafish can be altered to explore the specific biological pathways associated with addiction.

Zebrafish do have other qualities humans can learn from. Researchers at Duke University are studying proteins that enable a zebrafish to completely heal its spine -- even after it was severed. They hope this knowledge will someday lead to new therapies to repair damaged spinal cords in humans.

Spouse Criticism Makes Back Pain Worse

By Pat Anson, Editor

Not one likes being criticized. But people with chronic back pain take it harder – physically and emotionally – when having an argument with a loved one.

Even a brief fight with a spouse can significantly worsen lower back pain, according to the findings of a small study published in the journal Pain.

Researchers at Rush University in Chicago – who have been studying the emotional, cognitive and social aspects of pain – enrolled 71 couples in a study to see how patients with degenerative discs, spinal stenosis or herniated discs coped with criticism from a spouse.

Researchers watched as the couples engaged in a 10 minute discussion that focused on how the partner with back pain could improve their ability to cope with pain. The patients were then put through a structured activity that included walking, bending, lifting and sitting while the spouse watched.

Pain levels and how the couple interacted were coded by researchers, who watched for signs of hostility or criticism.

Patients who felt they were criticized by a spouse not only experienced more anxiety, anger and sadness, but their pain levels increased for as long as three hours. Women and patients who were depressed seemed most sensitive to criticism.

“Results support the hypothesis that spouse criticism and hostility - actually expressed or perceived -- may worsen CLBP (chronic low back pain) patient symptoms. Further, women patients and patients high in depressive symptoms appeared most vulnerable to spouse criticism/hostility,” wrote lead author John Burns, PhD, principal investigator at the Acute and Chronic Pain Research Lab at Rush University.

Researchers were surprised to see that even when a partner was supportive – and expressed concern about a patient's pain or gave “helpful” suggestions – the interaction was still perceived as negative by patients.

“Because the study required both patient and spouse to cooperate enough to participate, they generally got along just fine,” Burns told Reuters Health. “Even with these fairly happy couples, spouses uttered enough critical and hostile comments to negatively affect patient pain and function.”

Previous research has also found that how couples interact with each other can play a significant role in pain levels. A recent study found that even just holding hands reduces pain intensity.