Trump Budget Cuts Would Further Limit Pain Research

By Pat Anson, Editor

The Trump administration has proposed another $1.2 billion in budget cuts for the National Institutes of Health (NIH), which experts say could hamper already anemic efforts at developing new treatments for chronic pain.  Most of the reductions at NIH would come from research grant funding.

Only about 1 percent of the NIH budget is designated for pain research, even though more Americans suffer from pain than heart disease, diabetes and cancer combined.

The proposed $1.2 billion reduction in this year’s NIH budget is in addition to the $5.8 billion cut the Trump Administration has already proposed for the agency in 2018.

The $7 billion in savings will be used to help pay for an enhanced border wall with Mexico and increased military spending.

The White House Office of Management and Budget says the NIH budget for 2018 “eliminates programs that are duplicative or have limited impact on public health” and would “help focus resources on the highest priority research and training activities.”

"I will be the first one down lobbying against this," said Ann Romney, who suffers from multiple sclerosis and is the wife of former GOP presidential nominee Mitt Romney.

"Nothing comes from nothing. If you don't have that funding, there will be nothing," she told Yahoo News. "There will be no new treatments, there will be no new drug therapies. Progress in medicine will come to a halt."

Pain Research Already Limited

The lack of spending on pain research -- by both the government and the healthcare industry – was a problem long before the Trump administration came out with its budget plans.

In 2012, researchers at Johns Hopkins University estimated that chronic pain costs the U.S. economy up to $635 billion a year in healthcare costs and lost productivity. Yet the NIH spent only $358 million on pain research that year, according to journalist Judy Foreman in her book, “A Nation in Pain.”

“It is a huge burden with very little actual research going into it. And still a lot of unmet medical need,” said Gabriel Baertschi, CEO of Grünenthal, a German pharmaceutical company. “The odds of succeeding in pain research are lower than in other areas. It’s much more complex than other diseases in a sense that if you hit one target you are not necessarily resolving pain. Pain is multi-dimensional. That explains why from a research point of view you don’t always succeed.”

Grünenthal is a research-oriented company that focuses on finding new treatments for conditions such as bladder pain and Complex Regional Pain Syndrome (CRPS). Recently the FDA designated an experimental drug being developed by Grünenthal as a potential breakthrough therapy for CRPS. The company is now in advanced stages of clinical trials.

Because it’s smaller and privately owned, Baertschi says Grünenthal can afford to explore new treatments for rare diseases that “Big Pharma” companies are not interested in developing.

“Most of the companies that were active in pain have closed their pain research centers,” he told PNN in an interview last month. “I think a lot of companies are pulling out because the cost of developing pain drugs has been immense. If you look at the latest generation of pain drugs, it has cost billions of dollars.

“That has scared off companies and I think companies are more focused on areas where the returns are better from a pricing point of view. Because quite frankly, if you look at oncology you can get (drug) prices that are far better than for pain.”

Insurers Refuse to Pay for New Treatments

Another problem is insurance coverage. A few years ago the U.S. Food and Drug Administration pressured drug makers to develop abuse deterrent technology for opioids to reduce the risk of abuse and addiction. Some companies spent hundreds of millions of dollars developing abuse deterrent opioids that insurers now refuse to pay for because they are more expensive.

“Payers are a huge barrier to innovative therapies because they block coverage. Without insurance coverage there is little incentive to invest,” said Lynn Webster, MD, a leading expert and researcher in pain management, who is vice president of Scientific Affairs at PRA Health Sciences. 

“In the past 30 years there haven't been more than 3 new chemical entities approved by the FDA. One reason is that we don't understand enough about the different mechanisms generating pain,” Webster explained. “I see our current approach is similar to how cancer research was conducted 60 years ago.  Back then most cancers were treated with the same monotherapies.  Once research delved into the multi-mechanistic contributions to cancer, therapeutic advances were possible. We need to do the same for pain. And insurance has to pay for the innovations.”

“Pain is unfortunately penalized by society. People feel there is enough treatment available,” said Grünenthal’s Baertschi. “There are a lot of very good pain therapies out there. But there are quite a few areas, especially niche areas and specific pain types, that are not being treated adequately and that’s where we focus our research.”

One analyst said it is unlikely Congress will go along with the proposed cuts in the NIH budget because it funds politically popular programs.

"At worst, we believe NIH (funding) will remain flat in a continuing resolution if there is a government spending standoff," wrote Cowen analyst Doug Schenkel in a note to investors. "Although NIH funding hasn't kept up with inflation, the only time there were cuts to the agency in the past decade was when Congress' hand was forced by sequestration."

A Coalition to Save NIH Funding has also been formed to lobby against the budget cuts.

"We were dismayed to learn that the NIH is vulnerable to deep funding cuts," said Carrie Jones of JPA Health Communications, which is managing the coalition. "Each day America benefits from the innovation and scientific discoveries made at the NIH. We won't sit idly by and watch critical research be stifled."

Doctors and Pain Patients Often Disagree on Goals

By Pat Anson, Editor

If you’ve ever felt that you and your doctor are not on the same page when it comes to treating your chronic pain, you’re not alone.

A small study published in The Clinical Journal of Pain found that disagreements between primary care physicians and patients over priorities in pain management are common. Patients generally hope to reduce pain intensity and identify the pain’s cause, while physicians aim to improve physical function and reduce the side effects of opioid pain medication, such as dependency.

"We wanted to understand why discussions about pain between patients and doctors are often contentious and unproductive," said lead author Stephen Henry, MD, an assistant professor of internal medicine at University of California Davis.

"Primary care physicians treat the majority of patients with chronic pain, but they aren't always equipped to establish clear, shared treatment goals with their patients."

The study involved 87 patients receiving opioid prescriptions for chronic musculoskeletal pain and 49 internal or family medicine physicians at two UC Davis Medical Center clinics in Sacramento, California. In most cases, the patients were seeing their regular physicians. Patients receiving pain treatment as part of cancer or palliative care were excluded from the study.

Immediately following clinic visits between November 2014 and January 2016, the patients completed questionnaires to rate their experiences and rank their goals for pain management. The physicians also completed questionnaires about the level of visit difficulty, along with their own rankings of goals for the patient's pain management.

Nearly half of patients (48%) ranked reducing pain intensity as their top priority, while 22% said finding a diagnosis was most important to them. In contrast, physicians ranked improving physical function as the top priority for 41% of patients, while reducing medication side effects was most important for 26 percent of them.

Physicians also rated 41% of the visits with pain patients as "difficult" -- meaning their interactions were challenging or emotionally taxing. Primary care physicians usually rate about 15% of patient visits as difficult.

One surprise finding was that patients rated their office visits as fairly positive, even when their doctor did not. That may reflect the fact that patients tend to have positive relationships with their regular physicians, even though they don't always agree with them..

“Another possibility is that patients and physicians may not have realized that they prioritized different goals, because goals were not explicitly discussed during the visit. Some patients may assume that their treatment priority and their physicians’ treatment priority are the same, even when they are not,” Henry wrote. “Disagreements about goals may only become relevant during visits where patients and physicians disagree about treatment plans (e.g., whether to prescribe opioids).”

Henry says primary care physicians may have adapted to recommendations such as the CDC opioid guidelines, which emphasize functional goals and avoidance of long-term opioid therapy. Patients have yet to adapt to the guidelines and are still primarily interested in pain relief.

What can be done to help doctors communicate more effectively with their pain patients?

Henry recommends communication training for primary care physicians to ensure that patients are more aware of their goals. "It is critical for doctors and patients to be on the same page and not working at cross purposes," he said.

Bacteria Studies Give New Hope to IBD Patients

By Pat Anson, Editor

A new study is adding to the growing body of evidence linking gut bacteria to autoimmune and gastrointestinal diseases – research that could lead to new and more effective treatments.

Researchers at the University of Utah used animal studies to show that a certain type of yeast can aggravate symptoms of Inflammatory Bowel Disease (IBD). Their findings, published in the journal Science Translational Medicine, also suggest that allopurinol, a generic drug already on the market, could offer some relief.

IBD is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract, causing diarrhea, pain, fatigue and weight loss.

For years doctors have used the presence of yeast antibodies, specifically antibodies in the yeast Saccharomyces cerevisiae, to differentiate between Crohn’s disease and ulcerative colitis, two variations of IBD. But it was unclear the role that yeast played in relation to IBD.

“To me this was a huge hole in our understanding of the role of yeast in IBD and our health,” said June Round, PhD, an associate professor in pathology at the University of Utah School of Medicine.

Round and her research team studied two types of yeast that are common in healthy people and IBD patients. Saccharomyces cerevisiae, also called Baker’s yeast, is a prominent organism in the environment and in our food. Rhodotorula aurantiaca is also commonly found in the environment, as well as milk and fruit juice.

Scientists gave each type of yeast to laboratory mice that had been treated with chemicals to induce IBD-like symptoms. The symptoms worsened in mice fed S. cerevisiae, but not in those fed R aurantiaca.

“The mice fed S. cerevisiae experienced significant weight loss, diarrhea, bloody stool, just like a person with IBD,” said Tyson Chiaro, graduate student in Round’s lab.

Further study revealed that the mice fed S. cerevisiae had a higher concentration of nitrogen-rich compounds, called purines, than the mice fed R. aurantiaca. Unlike other yeasts, S. cerevisiae cannot break down purines that accumulate in the intestinal tract and produce uric acid. Uric acid exacerbates inflammation, which may worsen IBD symptoms.

When the mice were treated with allopurinol, a medication used to block the production of uric acid in gout patients, the drug significantly reduced their intestinal inflammation.

“Our work suggests that if we can block the mechanism leading to the production of uric acid, perhaps with allopurinol, IBD patients with a high concentration of S. cerevisiae antibodies may have a new treatment option to reduce inflammation, which could allow the intestine time to heal,” said Round.

E. Coli linked to IBD and spondyloarthritis

Another recent study has helped researchers identify E. coli bacteria found in people with Crohn's disease that can trigger inflammation associated with spondyloarthritis, a painful arthritic condition that affects the spine and joints.

Researchers used fecal samples from IBD patients to identify bacteria in the gut that were coated with antibodies called immunoglobulin-A (IgA) that fight infection. Using flow cytometry, in which fluorescent probes are used to detect IgA-coated bacteria, the researchers found the E. coli bacteria were abundant in fecal samples from patients with both Crohn's disease and spondyloarthritis.

"Our findings may allow us to develop diagnostic tools to stratify Crohn's patients with spondyloarthritis symptoms as well as patients at risk," said senior author Dr. Randy Longman, an assistant professor of medicine and director of the Jill Roberts Institute Longman Lab at Weill Cornell Medicine.

Longman and his research team found that patients with Crohn's disease and spondyloarthritis had high levels of Th17 cells, which help fight inflammation. The finding may help physicians select therapies that target inflammation in both the bowels and the joints.

"We knew there was smoke but we didn't know where the fire was," said Dr. Kenneth Simpson, a professor of small animal medicine at Cornell's College of Veterinary Medicine. "If we can block the ability of bacteria to induce inflammation, we may be able to kick Crohn's disease and spondyloarthritis into remission."

The study findings are also published in Science Translational Medicine

What Cavemen Used for Pain Relief

By Pat Anson, Editor

Neanderthals may be a lot smarter than we give them credit for. Especially when it comes to finding pain relief.

Ancient DNA extracted from the dental plaque of Neanderthals has revealed new insights into their behavior and diet, including their use of plant-based medicine to treat pain and illness.

An international team of researchers compared dental plaque from the jawbones of four Neanderthals found at ancient cave sites in Belgium (Spy Cave) and Spain (El Sidrón Cave). The four samples range from 42,000 to around 50,000 years old and are the oldest dental plaque ever to be genetically analyzed.

“Dental plaque traps microorganisms that lived in the mouth and pathogens found in the respiratory and gastrointestinal tract, as well as bits of food stuck in the teeth – preserving the DNA for thousands of years,” says Dr. Laura Weyrich, a research fellow at the University of Adelaide’s Australian Centre for Ancient DNA (ACAD), who was lead author of the groundbreaking study reported in the journal Nature.

RESEARCHERS IN EL SIDRON CAVE

“Genetic analysis of that DNA ‘locked-up’ in plaque, represents a unique window into Neanderthal lifestyle – revealing new details of what they ate, what their health was like and how the environment impacted their behavior.”

The researchers found that Neanderthals from Spy Cave were mostly meat eaters who consumed wooly rhinoceros and wild sheep, and supplemented their diet with wild mushrooms.

“Those from El Sidrón Cave on the other hand showed no evidence for meat consumption, but appeared instead to have a largely vegetarian diet, comprising pine nuts, moss, mushrooms and tree bark – showing quite different lifestyles between the two groups,” said professor Alan Cooper, Director of ACAD.

The analysis of one Neanderthal found at El Sidrón revealed another surprise. He probably had pain from a dental abscess on his jawbone, and also had signs of an intestinal parasite that causes acute diarrhea.

“Clearly he was quite sick. He was eating poplar, which contains the pain killer salicylic acid, and we could also detect a natural antibiotic mold not seen in the other specimens,” said Cooper. “Apparently, Neanderthals possessed a good knowledge of medicinal plants and their various anti-inflammatory and pain-relieving properties, and seem to be self-medicating.”

Salicylic acid is the active ingredient in aspirin; while certain types of mold – such as Penicillium – help the body fight off infections.

JAWBONE OF NEANDERTHAL FOUND IN EL SIDRON CAVE

“The use of antibiotics would be very surprising, as this is more than 40,000 years before we developed penicillin. Certainly our findings contrast markedly with the rather simplistic view of our ancient relatives in popular imagination,” says Cooper.

The researchers also found that Neanderthals and modern humans shared several disease-causing microbes, including the bacteria that cause dental cavities and gum disease.

Types of bacteria were closely associated with the amount of meat in the diet, with the Spanish Neanderthals grouping with ancient human ancestors in Africa. In contrast, the Belgian Neanderthal bacteria were similar to early hunter gatherers, and quite close to modern humans and early farmers.

“Not only can we now access direct evidence of what our ancestors were eating, but differences in diet and lifestyle also seem to be reflected in the commensal bacteria that lived in the mouths of both Neanderthals and modern humans,” said Professor Keith Dobney of the University of Liverpool.

“Major changes in what we eat have, however, significantly altered the balance of these microbial communities over thousands of years, which in turn continue to have fundamental consequences for our own health and well-being. This extraordinary window on the past is providing us with new ways to explore and understand our evolutionary history through the microorganisms that lived in us and with us.”

Why Women Feel Chronic Pain More Than Men

By Pat Anson, Editor

A new study may help explain why women are more likely to have chronic pain and are more sensitive to painful sensations than men.

It’s because their brains work differently.

In experiments on laboratory animals, researchers at Georgia State University found that immune cells in female rats are more active in regions of the brain involved in pain processing. Their study, published in the Journal of Neuroscience, found that when microglia cells in the brain were blocked, the female rats responded better to opioid pain medication and matched the levels of pain relief normally seen in males.

Women suffer from a higher incidence of chronic pain conditions such as fibromyalgia and osteoarthritis. And studies have found that they often have to take more morphine than men to get the same level of analgesia.

“Indeed, both clinical and preclinical studies report that females require almost twice as much morphine as males to produce comparable pain relief,” says Hillary Doyle, a graduate student in the Neuroscience Institute of Georgia State. “Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia.”

In healthy people, microglia cells survey the brain, looking for signs of infection or pathogens like bacteria. Morphine is perceived as a pathogen and activates the cells, causing the release of inflammatory chemicals such as cytokines. Researchers say this causes "a neuroinflammatory response that directly opposes the analgesic effects of morphine."

To test their theory, researchers gave male and female rats naloxone, a drug that reverses the effects of an opioid overdose, and found that it inhibits the microglia activation triggered by morphine.

“The results of the study have important implications for the treatment of pain, and suggests that microglia may be an important drug target to improve opioid pain relief in women,” said Dr. Anne Murphy, PhD, co-author of the study and associate professor in the Neuroscience Institute at Georgia State.

Murphy says her team’s finding may also help explain why women are significantly more likely to experience chronic pain conditions than men.

A recent study at UCLA and UC Irvine found that microglial cells in both female and male rats can be activated by chronic pain.  The researchers found that brain inflammation in rodents caused by chronic nerve pain led to accelerated growth of microglia. The cells triggered chemical signals in the brain that restricted the release of dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers.

Early Detection and Diet May Help Prevent Osteoporosis

By Pat Anson, Editor

The key to good bone health – and preventing fractures later in life – may lie in anti-inflammatory diets and earlier detection of bone loss, according to two new studies.

Researchers at the University of Michigan are studying new ways to identify women at risk of osteoporosis, a loss in bone density that raises the risk of fractures and disability. Breaking a bone in your spine or hip doubles your chances of developing chronic widespread body pain, especially if you are older.

"It's been considered a silent disease," says Karl Jepsen, PhD, associate chair of research and professor of orthopaedic surgery at Michigan Medicine. "One of the biggest challenges when you're looking at age-related bone fragility is to identify people who will fracture."

Jepsen is the lead author of a study published in the Journal of Bone and Mineral Research, which followed nearly 200 women for 14 years as they transitioned through menopause.

"Current identification for bone fragility takes place when the patient is around 65 years of age," Jepsen explains.

"We were hopeful that this study would give us an opportunity to identify those patients as early as 30 years before they fracture based on their bone traits. That means we would have an opportunity to intervene before the fracture happens, instead of after the fact."

Jepsen and his colleagues started following the women in 1996. Participants who enrolled had to be between 42 and 52 years of age and had at least one menstrual period in the previous three months. The women had bone density scans and other tests annually to measure changes in their bone mineral density.

Researchers found that the women experienced a wide variation in bone mineral content and bone area within the hip as they went through menopause, a finding that was unexpected.

"Our results were opposite to all expectations of how we assumed this would work," Jepsen says. "We found some women appeared to have hip bones that were increasing in strength during the menopausal transition while others seemed to be losing strength."

Jepsen said his study demonstrates that bone changes can be tracked individually in women during menopause, when treatment can begin earlier to prevent bone loss. Hormones and bisphosphonate drugs are currently used to help strengthen bones.

“Our goal is to use simple bone traits to identify those women that may benefit from early intervention when it comes to bone fragility, instead of the current strategy, which treats individuals after they have lost appreciable bone mass and strength," he said.

Anti-Inflammatory Diet Improves Bone Health

Anti-inflammatory diets -- which tend to be high in vegetables, fruits, fish and whole grains -- could boost bone health and prevent fractures, according to a study at The Ohio State University.

Researchers analyzed dietary data from over 160,000 women enrolled in the landmark Women's Health Initiative by assigning inflammation scores based on 32 foods that the women reported consuming. Researchers also looked at bone-mineral-density data from over 10,000 women and collected fracture data for the entire study group.

They found a correlation between high-inflammatory diets and fractures in post-menopausal younger than 63. Women with the least-inflammatory diets also lost less bone mineral density.

"This suggests that as women age, healthy diets are impacting their bones," said Tonya Orchard, an assistant professor of human nutrition at Ohio State's Food Innovation Center. "These women with healthier diets didn't lose bone as quickly as those with high-inflammation diets, and this is important because after menopause women see a drastic loss in bone density that contributes to fractures,"

The study, which appears in the Journal of Bone and Mineral Research, was observational -- meaning it does not definitively link diet to bone health. But it adds to a growing body of evidence that inflammation can increase osteoporosis risk.

"By looking at the full diet rather than individual nutrients, these data provide a foundation for studying how components of the diet might interact to provide benefit and better inform women's health and lifestyle choices," said Rebecca Jackson, the study's senior author and director of Ohio State's Center for Clinical and Translational Science.

Previous studies have connected high levels of inflammatory markers in the blood to bone loss and fractures in older women and men. The new findings suggest that women's bone health could benefit when they choose a diet higher in beneficial fats, plants and whole grains.

Experts Say Weather’s Not to Blame for Your Pain

By Pat Anson, Editor

The age old debate over weather’s impact on pain is heating up again with new research indicating that cold, rainy weather has no impact on symptoms associated with back pain or osteoarthritis.

Researchers at The George Institute for Global Health in Australia say damp weather makes people more aware of their pain, but the symptoms disappear as soon as the sun comes out – suggesting there’s a psychological cause.

“Human beings are very susceptible so it’s easy to see why we might only take note of pain on the days when it’s cold and rainy outside, but discount the days when they have symptoms but the weather is mild and sunny,” said Professor Chris Maher, director of the George Institute’s Musculoskeletal Division.  

“The belief that pain and inclement weather are linked dates back to Roman times. But our research suggests this belief may be based on the fact that people recall events that confirm their pre-existing views.”

Maher and his colleagues conducted two studies involving nearly 1,000 Australians with back pain and 345 people with osteoarthritis.

Using weather data from the Australian Bureau of Meteorology, researchers compared the weather at the time patients first noticed pain with weather conditions one week and one month before the onset of pain as a control measure. 

Results showed no association between back pain and temperature, humidity, air pressure, wind direction or precipitation. Warmer temperatures did slightly increase the chances of lower back pain, but the amount of the increase was not clinically important. 

A previous study on back pain and weather at The George Institute had similar findings, but received widespread criticism from the public.

“People were adamant that adverse weather conditions worsened their symptoms so we decided to go ahead with a new study based on data from new patients with both lower back pain and osteoarthritis. The results though were almost exactly the same – there is absolutely no link between pain and the weather in these conditions,” said Maher.

The back pain study was published in the journal Pain Medicine. The study on osteoarthritis was published in Osteoarthritis and Cartilage.

“People who suffer from either of these conditions should not focus on the weather as it does not have an important influence on your symptoms and it is outside your control,” said Associate Professor Manuela Ferreira.

The Greek philosopher Hippocrates in 400 B.C was one of the first to note that changes in the weather can affect pain levels. Although a large body of folklore has reinforced the belief that there is a link between weather and pain, the science behind it is mixed.

PNN readers say there’s little doubt in their minds that there’s a connection.

“I totally agree that rainy weather does affect pain. I have osteoarthritis and fibromyalgia, and pain is most severe when there is a change happening in the weather especially rain,” wrote Dee.

“It's been well established that the source of weather-related pain is a direct result from the variance in barometric pressure,” said Judith Bohr. “Changes in the intensity of that pressure is felt more acutely in the parts of the body where there are injuries, degenerative changes, surgeries, wherever there is an increased sensitivity because of inflammation.”

Others say they can predict the weather based on their pain levels.

“So many sunny days and I've said it’s going to rain. People thought I was crazy for a while, but now they know,” said Ashley. “My kids are always asking if it’s going to rain.”

A study currently underway in England suggests there is a connection between weather and pain. Over 9,000 people are participating in The University of Manchester’s Cloudy with a Chance of Pain project, using a special app on their smartphones to record their daily pain levels. The app also captures hourly weather conditions.

Preliminary results show that as the number of sunny days increase, the amount of time participants spend in severe pain decreases. When the weather turns rainy and cloudy, however, the amount of time people spent in severe pain increases.

Can Gum Disease Cause Rheumatoid Arthritis?

By Pat Anson, Editor

Scientists have long suspected that pathogens and bacterial infections may play a role in the development of autoimmune diseases such as rheumatoid arthritis (RA). Now there is evidence that a bacterium associated with chronic gum infections may trigger an inflammatory response characteristic of RA, a discovery that could lead to new ways to treat and prevent the disease.

"This research may be the closest we've come to uncovering the root cause of RA," said Maximilian Konig, MD, a former Johns Hopkins University School of Medicine fellow now at Massachusetts General Hospital.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. About 1.5 million Americans and one percent of adults worldwide suffer from RA. There is no cure for the disease and treatments only focus on slowing its progression.

In a study of nearly 200 RA patients, Konig and his colleagues found that nearly half had antibodies against Aggregatibacter actinomycetemcomitans in their blood.  

The level of infection with the bacteria was similar in patients with periodontal (gum) disease, but quite different in healthy patients, only 11 percent of whom tested positive for A. actinomycetemcomitans.

An infection with A. actinomycetemcomitans appears to induce the production of citrullinated proteins, which are suspected of activating the immune system and driving the cascade of events leading to RA.

"This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years," says Felipe Andrade, MD, a senior study investigator and associate professor of Medicine at the Johns Hopkins University School of Medicine.

Andrade cautions that over half of the study participants with RA had no evidence of an infection with A. actinomycetemcomitans, which may indicate that other bacteria in the gut, lung or elsewhere could be involved. He says more research is needed to determine if there is a cause and effect relationship between bacteria and RA.

"If we know more about the evolution of both combined, perhaps we could prevent rather than just intervene," he said.

The Johns Hopkins study is published in the journal Science Translational Medicine.

Scientists have observed an association between periodontal disease and RA since the early 1900s, and have suspected that both diseases may be triggered by a common factor. In the last decade, studies have focused on a bacterium known as Porphyromonas gingivalis, which is found in patients with gum disease. However, research has so far failed to corroborate such a link.

Researchers in the current study found inflammation in the joints of RA patients that was similar to the inflamed gums of patients with periodontal disease, an inflammatory process known as hyper-citrullination.

Citrullination occurs naturally in everyone as a way to regulate the function of proteins. But in people with RA, the process becomes hyperactive, resulting in the abnormal accumulation of citrullinated proteins. This drives the production of antibodies against proteins that create inflammation and attack a person's own tissues, the hallmark of RA.

Zebrafish Could Help Repair Human Spinal Cord Injuries

By Pat Anson, Editor

A freshwater fish popular in many home aquariums might hold the key to repairing damaged spinal cords in humans.

In a study published in the journal Science, Researchers at Duke University say the zebrafish is able to completely heal its spine -- even after it was severed -- because of a protein that helps to rebuild damaged spinal nerves.

"This is one of nature's most remarkable feats of regeneration," said the study's senior investigator Kenneth Poss, a professor of cell biology and director of the Regeneration Next initiative at Duke. "Given the limited number of successful therapies available today for repairing lost tissues, we need to look to animals like zebrafish for new clues about how to stimulate regeneration."

Poss and his colleagues say when the zebrafish's spinal cord is severed, dozens of genes are activated by the injury. Within days, they produce new molecules and proteins to bridge the gap between the severed spine. One of the proteins, called connective tissue growth factor (CTGF), appears to play a key role in regenerating glia nerve cells.

Within 8 weeks, new nerve tissue has filled the gap in the spinal cord and the zebrafish has fully reversed its paralysis.

"The fish go from paralyzed to swimming in the tank. The effect of the protein is striking," said lead author Mayssa Mokalled, a postdoctoral fellow at Duke. “We thought that these glial cells and this gene must be important.”

The zebrafish belongs to the minnow family and is native India, Pakistan and the Himalayan region. It is widely used in scientific research because if it’s regenerative abilities, and was the first vertebra to be cloned. A 2012 study published in The Journal of Neuroscience also documented the fish’s ability to bridge the gap between spinal nerve cells.

Humans and zebrafish share many genes, and the human CTGF protein is nearly 90% similar in its amino acids to the zebrafish’s.

Remarkably, when Duke researchers added the human version of CTGF to the severed spinal cords in zebrafish, it boosted regeneration and the fish began swimming two weeks after the injury.

Healing damaged spinal cords is more complex in mammals, in part because scar tissue forms around the injury. Researchers say CTGF is probably not sufficient on its own for people to regenerate their spinal cords, but further animal studies are needed.

"Mouse experiments could be key," Mokalled says. "When do they express CTGF, and in what cell types?"

The Duke research team also plans to follow up with other proteins that were secreted after injury, which may provide further hints into the zebrafish's ability to regenerate nerve cells.

"I don't think CTGF is the complete answer, but it's a great thing to have in hand to inform new ways to think about the real challenge of trying to improve regeneration," Poss said.

This research was supported by the National Institutes of Health, the Max Planck Society, and Duke University School of Medicine. Duke is seeking patent applications related to the research.

Scientists Use Light and Sound to Reduce Pain

By Pat Anson, Editor

British researchers have found that pain can be significantly reduced if the brain if “tuned in” to a particular frequency, a discovery that could potentially lead to new visual and sound therapies to treat chronic and acute pain.

"This is very exciting because it provides a potentially new, simple and safe therapy that can now be trialed in patients,” said Professor Anthony Jones, director of the University of Manchester Pain Consortium. “The potential is for this to be another treatment for chronic pain.”

Jones and his colleagues say nerve cells in different parts of the brain communicate with each other using different frequencies.  

Nerves in the front of the brain associated with a placebo analgesic effect are tuned in at 9-12 cycles per second, and apparently use that frequency to influence how other parts of the brain process pain.

To test their theory, researchers had 64 healthy volunteers wear goggles and headphones, and exposed them to different flashing lights and sounds while heat pain was induced with a laser on the back of their arms.

The volunteers who were exposed to an alpha frequency at 9-12 cycles felt significantly less pain than those who were exposed to other light and sound levels.

“This study provides new evidence that visual and auditory entrainment in the alpha range can influence the perception of acute pain independently of arousal and negative emotional influences,” the researchers said. “Overall, visual entrainment produced a larger effect than auditory entrainment in the mid- and lower alpha frequencies. This provides further evidence that external stimulation can modulate pain perception and requires further study to ascertain its relevance to clinical pain states.”

Further studies are needed to test the effectiveness of alpha wave therapy in patients with different pain conditions. Researchers say the simplicity and low cost of the technology should facilitate more clinical studies.

"It is interesting that similar results were obtained with visual and auditory stimulation, which will provide some flexibility when taking this technology into patient studies,” said Dr. Chris Brown, a lecturer in Psychology at The University of Liverpool who was involved in the research. “This might be particularly useful for patients having difficulty sleeping because of recurrent pain at night."

The study, which was self-funded as part of a PhD project, is being published in the European Journal of Pain.

What Grade Should Your State Get for Pain Care?

By Pat Anson, Editor

Millions of Americans who suffer from chronic pain are having trouble finding doctors, obtaining pain medication, and getting health insurance to cover their treatment. So imagine their surprise when a recent study gave passing grades to all 50 states for their pain care policies and said there was “an overall positive policy environment across the nation.”  

“We saw that report and were disgusted. At a time when chronic pain patients across the country are losing their medications and treatments to manage their pain, giving no state a grade below a 'C' is insulting,” said Amanda Korbe, who suffers from Reflex Sympathetic Dystrophy (RSD) and is a founder of Patients Not Addicts, a patient advocacy group.

“Achieving Balance in State Pain Policy” was released over the summer by the Pain and Policy Studies Group at the University of Wisconsin School of Medicine. The report looked at state laws and regulations in 2015 that governed drugs, prescribing and pain care practices.

“This evaluation is meant to identify relevant language in each state’s legislation or regulatory policies that have the potential to influence appropriate treatment of patients with pain, including controlled medication availability,” the study says.

The study gave 13 states an “A” for the quality of their pain care policies:  Alabama, Georgia, Idaho, Iowa, Kansas, Maine, Michigan, Oregon, Rhode Island, Vermont, Virginia, Washington and Wisconsin.

Thirty-one states were given B’s and the rest got C’s. No state was given a failing grade. A complete list of grades for all 50 states and Washington DC can be seen at the end of this story.

“I know that as an Oregon chronic pain patient, I can say my state does not deserve an 'A' right now. We have too many under treated patients, and too many that can't get care at all. For those of us that can't get proper pain management, these high grades are a slap in the face. It invalidates our experiences and struggles to get proper pain management,” said Korbe.

“Would pain management be in such a sorry state if these ‘grades’ actually meant anything? I personally think they are worthless,” said Janice Reynolds, a retired nurse, pain sufferer and patient advocate in Maine, which received an “A” grade.  

Rather than look at state policies and regulations, Reynolds said the study would be more meaningful if it examined whether opioids were being prescribed appropriately, if patients were having a difficult time finding providers, and if untreated pain was leading to more suicides.

“Every state would get a D or F if this was done,” she said.

Study Looked at Pain Policy, Not Practice

“To really look at this comprehensively, it requires a broader analysis to really get an understanding of things,” admits Aaron Gilson, PhD, the lead researcher for the study, which was funded by the American Cancer Society.

Gilson told Pain News Network the study only looked at state policies and regulations as they exist on paper – not how they were being implemented or even if they were effective.

“There’s not necessarily a 100% correlation between policies and practice. The policies in and of themselves don’t create barriers to pain management that we’ve identified. The grade that each state earned is really based on policies that can improve pain management for patients when put into practice,” he said.  

“Sound policy that's not implemented is only words wasted,” says Anne Fuqua, a pain sufferer and patient advocate, whose home state of Alabama was given an “A” grade.

“I'd give Alabama a 'C' for being better than the worst states like Ohio, Kentucky, Tennessee, Florida, West Virginia, Washington, and Oregon.  On paper the policy is excellent and it deserves the 'A' it gets. It just needs to be implemented.”

The study also didn’t look at insurance reimbursement issues or how doctors are responding to federal policies such as the CDC’s opioid prescribing guidelines, which were not released until this year and are having a chilling effect on both patients and doctors.    

Gilson said the methodology used to prepare the next pain care policy report – which was first released in 2000 – probably needs to be updated.

“That’s the first order of business in terms of continuing to do this, to really understand how policies have changed,” Gilson said. “I think it’s really time to examine the criteria that we use to see to what extent we might be missing policy because we’re not looking at the right thing, because barriers are erected in other ways than when we constructed this type of evaluation 16 years ago.”

Patient Survey Underway

One way to better understand those barriers is to simply ask patients what they are experiencing.

“Legitimate patients report the entire move to reduce (opioid) production and restrict prescribing is having a profoundly negative impact on their treatment protocols. Understanding how they are being impacted is important,” says Terri Lewis, PhD, a patient advocate and researcher.

Lewis is conducting a lengthy and detailed 29-question survey of pain patients to see how they are being impacted by efforts to reduce opioid prescribing. To take her online survey, click here.

Lewis will be able to breakdown the data state-by-state to get a real indication of how pain care policies and practices are being implemented.

“We will get that patient voice into this conversation,” she says. “Reports from patients are important and add value to the public conversation.  Reports will be analyzed and compared to months long data collection to look at trends, the impact of increasing restrictions, the fear of physicians to treat patients in this climate, and the influence of other factors like insurance restrictions and red flagging. This is a complex problem.”

SOURCE: PAIN & POLICY STUDIES GROUP, UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE

Placebo Effect is All in Our Heads

By Pat Anson, Editor

A new study has given researchers a better understanding why some people given a simple sugar pill will say it significantly reduces their pain.

It’s all in their heads.

Using functional magnetic resonance brain imaging (fMRI), scientists at the Northwestern Medicine and the Rehabilitation Institute of Chicago (RIC) have identified for the first time the region of the brain that's responsible for the "placebo effect" in pain relief. It’s an area in the front part of the brain -- called the mid frontal gyrus -- that also plays a key role in our emotions and decision making.

In two clinical trials involving 95 patients with chronic pain from osteoarthritis, researchers found that about half of the participants had mid frontal gyrus that had more connectivity with other parts of the brain and were more likely to respond to the placebo effect.

The use of fMRI images to identify these “placebo responders” and eliminate them from clinical trials could make future research far more reliable. It could also lead to more targeted pain therapy based on a patient’s brain images, instead of a trial-and-error approach that exposes patients to ineffective and sometimes dangerous medications.

"Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials," said Marwan Baliki, PhD,  a research scientist at RIC and an assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

“This can help us better conduct clinical studies by screening out patients that respond to placebo and we can just include patients that do not respond. And we can measure the efficacy of a certain drug in a much more effective manner.”

Baliki told Pain News Network that differences in the brain could explain why some prescription drugs – such as Lyrica (pregabalin) – are effective in giving pain relief to some patients, but not for others.

“If we do the same with Lyrica, maybe we can find another area of the brain that can predict the response to that drug,” he said.

The study findings are being published in PLOS Biology.

"The new technology will allow physicians to see what part of the brain is activated during an individual's pain and choose the specific drug to target this spot," said Vania Apkarian, a professor of physiology at Feinberg and study co-author. "It also will provide more evidence-based measurements. Physicians will be able to measure how the patient's pain region is affected by the drug."

Currently, most clinical studies involving pain are conducted on healthy subjects in controlled experimental settings. Those experiments usually induce acute pain through immersion in cold water, pressure or some other type of applied pain. Baliki says there are significant differences between acute and chronic pain, and the experiments often translate poorly in clinical settings where pain is usually chronic.   

Researchers Discover ‘Brain Signature’ for Fibromyalgia

By Pat Anson, Editor

Researchers at the University of Colorado Boulder have discovered a “brain signature” that identifies fibromyalgia with 93 percent accuracy, a potential breakthrough in the diagnosis and treatment of a chronic pain condition that five million Americans suffer from.

Fibromyalgia is a poorly understood disorder characterized by deep tissue pain, headaches, fatigue, anxiety, depression and insomnia. The cause of fibromyalgia is unknown and there is no universally accepted way to diagnose or treat it.

The CU Boulder researchers used MRI scans to study brain activity in a group of 37 fibromyalgia patients and 35 control patients, who were exposed to a series of painful and non-painful sensations.

The researchers were able to identify three neurological patterns in the brain that correlated with the pain hypersensitivity typically experienced with fibromyalgia.

UNIVERSITY OF COLORADO BOULDER

"The potential for brain measures like the ones we developed here is that they can tell us something about the particular brain abnormalities that drive an individual's suffering. That can help us both recognize fibromyalgia for what it is - a disorder of the central nervous system - and treat it more effectively," said Tor Wager, director of CU Boulder’s Cognitive and Affective Control Laboratory.

If replicated in future studies, the findings could lead to a new method to diagnosis fibromyalgia with MRI brain scans. Patients who suffer from fibromyalgia have long complained that they are not taken seriously and have to visit multiple doctors to get a diagnosis.

"The novelty of this study is that it provides potential neuroimaging-based tools that can be used with new patients to inform about the degree of certain neural pathology underlying their pain symptoms," said Marina López-Solà, a post-doctoral researcher at CU Boulder and lead author of a study published in the journal Pain. "This is a helpful first step that builds off of other important previous work and is a natural step in the evolution of our understanding of fibromyalgia as a brain disorder."

One patient advocate calls the use of MRI brain scans a breakthrough in fibromyalgia research.

"New cutting-edge neurological imaging used by CU Boulder researchers advances fibromyalgia research by light years," said Jan Chambers, founder of the National Fibromyalgia & Chronic Pain Association. "It allows scientists to see in real time what is happening in the brains of people with fibromyalgia. 

"In fibromyalgia, the misfiring and irregular engagement of different parts of the brain to process normal sensory stimuli like light, sound, pressure, temperature and odor, results in pain, flu-like sensations or other symptoms.  Research also shows that irregular activity in the peripheral nervous system may be ramping up the central nervous system (brain and spinal cord).  So the effect is like a loop of maladjustment going back and forth while the brain is trying to find a balance.  This extra brain work can be exhausting." 

The theory that fibromyalgia is a neurological disorder in the brain is not accepted by all. Other experts contend it is an autoimmune disorder or even a “symptom cluster” caused by multiple chronic pain conditions. And some doctors still refuse to accept fibromyalgia as a disease.

One company has already developed a diagnostic test for fibromyalgia – and it’s not a brain scan. EpicGenetics has a blood test that looks for protein molecules produced by white blood cells. Fibromyalgia patients have fewer of these molecules than healthy people and have weaker immune systems, according to the founder of EpicGenetics. But critics have called the blood test “junk science” that is backed up by little research.

Wheat Protein Could Worsen Chronic Illness

By Pat Anson, Editor

Gluten isn’t the only reason why some people should avoid eating wheat.

German researchers have discovered a second protein in wheat that triggers inflammation and worsen symptoms of multiple sclerosis, lupus, rheumatoid arthritis and other chronic illnesses. The finding could help explain why some people who are not gluten intolerant and do not have celiac disease still benefit from going on a gluten-free diet.

Researchers say a family of proteins called amylase-trypsin inhibitors (ATIs) make up only about 4% of the protein found in wheat. But they can trigger powerful immune system reactions outside the digestive system, in the lymph nodes, kidneys, spleen and brain.

"As well as contributing to the development of bowel-related inflammatory conditions, we believe that ATIs can promote inflammation of other immune-related chronic conditions outside of the bowel,” said lead researcher, Professor Detlef Schuppan of Johannes Gutenberg University.

“The type of gut inflammation seen in non-celiac gluten sensitivity differs from that caused by celiac disease, and we do not believe that this is triggered by gluten proteins. Instead, we demonstrated that ATIs from wheat, that are also contaminating commercial gluten, activate specific types of immune cells in the gut and other tissues, thereby potentially worsening the symptoms of pre-existing inflammatory illnesses.”

Schuppan presented his findings at United European Gastroenterology Week. He said future clinical studies will explore the role that ATIs play on chronic health conditions in more detail.

"We are hoping that this research can lead us towards being able to recommend an ATI-free diet to help treat a variety of potentially serious immunological disorders," said Schuppan.

Celiac disease is a gastrointestinal inflammation caused by the ingestion of wheat, barley, rye, and other foods containing gluten. About 1-2% of the population has celiac disease, but most cases go undiagnosed and untreated.

People with non-celiac gluten sensitivity (NCGS) may also develop gastrointestinal symptoms, as well as headaches, chronic fatigue, fibromyalgia and allergies. Abdominal pain and irregular bowel movements are frequently reported with NCGS, which can make it difficult to distinguish from irritable bowel syndrome (IBS).

The symptoms typically appear after the consumption of gluten-containing food and improve rapidly on a gluten-free diet, even though gluten does not appear to cause the condition. Schuppan says the real culprit may be ATIs.

"Rather than non-celiac gluten sensitivity, which implies that gluten solitarily causes the inflammation, a more precise name for the disease should be considered," he said.

The Importance of Participating in Pain Research

By Barby Ingle, Columnist

Over the years I have participated in many research studies and potential new treatments. One such study was just published in the Journal of Translational Medicine by Drs. Garabed G. Demerjian, Andre Barkhordarian and Francesco Chiappelli.

So many people over the years meet me and soon realize that I have a device called an oral orthotic in my mouth. This “OO” as I lovingly call it has helped me so much, and now there is published research behind what it is doing for me.

Back in 2002 when I developed Reflex Sympathetic Dystrophy, I lost partial vision in my right eye. I saw many eye doctors and ENT (ear, nose and throat) specialists who were unable to pinpoint where the breakdown in the nerves were. They hypothesized that it was due to inflammation from the RSD cutting off a nerve pathway.

Within 30 seconds of putting in the OO, I had my vision back after 10 years of being told that I would never see properly again. My world is now brighter with the OO, literally.

I also had improvement in pain levels affecting my entire body. I have been able to get my infusion therapy minimized to only 1 or 2 boosters a year and get off all daily pain medication. I also have had improvement in my balance, coordination, dystonia, memory and mood. My migraines and headaches are less frequent, and although weather and pressure changes still affect me, it is not to the extent it was prior to my oral orthotic use.

The research doctors and my treating doctor, Garabed Demerjian, approached their study with an individualized approach that they made measurable for each patient who participated. I underwent multiple MRIs, cat-scans, X-rays, synovial fluid testing, psychological testing, and saliva testing.

These tests were done in an effort to quantify the outcome and show the effectiveness of the oral orthotic. I participated in the study in 2015, about three years after getting my OO. I already knew that the tests were going to show amazing results. That is great for the scientific community and for advancing new treatment options.

Traditional research in the health sciences usually involves control and experimental groups of patients, and descriptive and statistical measurements obtained from samples in each group. The research I was part of used a novel model known as translational medicine, which "translates" research into more effective healthcare -- a "bench-to-bedside" approach. This type of research is increasingly becoming more established in modern contemporary medicine.

I often say that each patient is different. Our biological makeup and life experiences mean disease often affects us in different ways – making a one-size-fits-all approach to medicine impractical. Science is seeing this too. It’s becoming more focused on translational research for the ultimate benefit of each individual patient. This is what we need.

I know and understand that being part of a research study is not for everyone. It doesn’t always go as great as it did for me. But stepping up and trying something that can benefit others is very rewarding.

I thank all of the research doctors and scientists who are making a difference in our lives. It can take years of research before they see actual results, and they are not always recognized for their efforts. I find it hard to express the full gratitude they deserve. Thank you to our researchers in the chronic pain community.

Barby Ingle suffers from Reflex Sympathetic Dystrophy (RSD) and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics.

More information about Barby can be found on her website.

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.