Stem Cell Vaccine Could Reverse Arthritis

By Pat Anson, Editor

A team of researchers has successfully used gene-editing technology to “rewire” mouse stem cells to fight inflammation – a finding that could pave the way for a new class of biologic drug that replaces cartilage and protect joints from damage caused by arthritis.

The stem cells, known as “smart” cells (stem cells modified for autonomous regenerative therapy), were developed at Washington University School of Medicine and Shriners Hospitals for Children in St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics in North Carolina.

The research findings are published in the journal Stem Cell Reports.

"Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said senior author Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University School of Medicine.

Guilak and his colleagues grew mouse stem cells in a test tube and then used a gene-editing tool called CRISPR to remove a gene that plays a key role in inflammation. That gene was replaced with a gene that releases a biologic drug that combats inflammation.

Within a few days, the modified stem cells grew into cartilage cells and produced cartilage tissue. Further experiments showed that the engineered cartilage was protected from inflammation.

"We hijacked an inflammatory pathway to create cells that produced a protective drug," explained Jonathan Brunger, PhD, the paper's first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

IMAGE CREDIT: ELLA MARUSHCHENKO

Many current biologic drugs used to treat arthritis – such as Enbrel, Humira and Remicade -- attack an inflammation-promoting molecule called TNF-alpha. But the problem with these drugs is that they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

"We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body," said Guilak. “If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint."

Researchers have begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases. If the work can be replicated in living laboratory animals and then developed into a clinical therapy, the cartilage grown from stem cells would respond to inflammation by releasing a drug that protects them from further damage.

"When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation," Guilak explained. "We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it's possible we could make stem cells that would sense glucose and turn on insulin in response.

"The ability to build living tissues from 'smart' stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine."

Farshid Guilak and co-author Vincent Willard have a financial interest in Cytex Therapeutics, a startup founded by some of the investigators. They may license the technology and realize financial gain if it is eventually is approved for clinical use.

Guilak and his colleagues at Cytex have also used stem cells to grow new cartilage that could someday be implanted into arthritic hips, delaying or eliminating the need for hip replacement surgery.

Stem cells are found throughout the body and are increasingly being used to develop new treatments to repair damaged tissue and reduce inflammation. The Food and Drug Administration considers most stem cell treatments experimental because their safety and efficacy haven’t been proven through clinical studies.

High Fat Diet Raises Osteoarthritis Risk

By Pat Anson, Editor

Saturated fatty acids are prime suspects in the onset of osteoarthritis, according a new study by Australian researchers who say fat changes the composition of cartilage, particularly in the hip and knee.

It’s one of the first studies to look at the association between osteoarthritis and saturated fatty acids found in foods such as butter, coconut oil, palm oil and animal fat.

When combined with simple carbohydrates in a high-fat, high carbohydrate diet – often called "junk food" – researchers found that fatty acids weaken cartilage and produce osteoarthritis-like changes in the knee.

"We also found changes in the bone under the cartilage on a diet rich in saturated fat," said Professor Yin Xiao of Queensland University of Technology’s Institute of Health and Biomedical Innovation. "Our findings suggest that it's not wear and tear but diet that has a lot to do with the onset of osteoarthritis

"Saturated fatty acid deposits in the cartilage change its metabolism and weaken the cartilage, making it more prone to damage. This would, in turn, lead to osteoarthritic pain from the loss of the cushioning effect of cartilage.”

Osteoarthritis is a joint disorder that leads to progressive joint damage. It can affect any joint in the body, but is most commonly felt in weight bearing joints such as the knees and hips. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis.

Xiao and his colleagues tested a variety of saturated fats and found that long term use of animal fat, butter and palm oil was the most damaging to cartilage. There was less damage caused by  lauric acid, a saturated fatty acid found in coconut oil.

"Interestingly, when we replaced the meat fat in the diet with lauric acid we found decreased signs of cartilage deterioration and metabolic syndrome so it seems to have a protective effect," said Sunder Sekar, a PhD student.

"Replacement of traditional diets containing coconut-derived lauric acid with palm oil-derived palmitic acid or animal fat-derived stearic acid has the potential to worsen the development of both metabolic syndrome and osteoarthritis."

Professor Xiao's previous research has found that antioxidants and anti-cholesterol drugs could slow the progression of joint damage caused by fatty acids.

The study was funded by the Prince Charles Hospital Research Foundation.

Study Questions Value of Knee Replacement Surgery

By Pat Anson, Editor

New research is raising questions about the value of knee replacement surgeries, one of the fastest growing elective procedures in the United States.

In an analysis of over 7,400 patients with osteoarthritis who had knee replacement surgeries, researchers concluded the procedure often had minimal effects on quality of life and wasn’t worth the cost. But when the surgeries are performed on patients with more severe knee pain, their effectiveness increases, researchers reported in The BMJ.

The annual rate of total knee replacements in the U.S. has doubled since 2000, with more than 640,000 surgeries now performed annually at a cost of $10.2 billion.

"Given its limited effectiveness in individuals with less severely affected physical function, performance of total knee replacement in these patients seems to be economically unjustifiable," wrote lead author Bart Ferket, MD, an assistant professor at the Icahn School of Medicine at Mount Sinai in New York City.

"Considerable cost savings could be made by limiting eligibility to patients with more symptomatic knee osteoarthritis,"

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis, and those numbers are expected to grow as the population ages.

Ferket and his colleagues found that about a third of the patients who had their knees replaced continued to experience chronic pain after the procedure. Their quality of life generally improved, but the change was small. The improvement in quality of life was higher when patients with lower physical scores before surgery were operated on.

“The practice of total knee replacement as performed in a recent U.S. cohort of patients with knee osteoarthritis had minimal effects on quality of life. If the procedure were restricted to patients with more severe functional status, however, its effectiveness would rise, with practice becoming economically more attractive,” they concluded.

"Our findings emphasize the need for more research comparing total knee replacement with less expensive, more conservative interventions, particularly in patients with less severe symptoms.”

Previous studies have also questioned the value of many knee surgeries. A five year study of 175 knee replacement patients by the National Institutes of Health found that over a third of the surgeries were inappropriate. Many patients had pain and other symptoms that were too mild to justify having their knees replaced.  

Another study found that arthroscopic knee surgery is “not an economically attractive treatment option” compared to physical therapy, exercise and medication.

In arthroscopic surgery, a doctor makes a small incision in the knee and inserts a tiny camera and instruments to repair damaged ligaments or torn meniscus. Arthroscopic surgery is far less invasive than a total knee replacement. Depending on insurance, hospital charges and the surgeon, arthroscopic surgeries cost about $4,000.  A total knee replacement costs about $28,000 according to HealthCare Bluebook.

Lady Gaga May Not Have Rheumatoid Arthritis

By Pat Anson, Editor

Lady Gaga has not publicly disclosed that her chronic hip pain is caused by rheumatoid arthritis.

In a cover story published in Arthritis Magazine, the 31-year old entertainer appears to be quoted as saying, “I fought RA pain with my passion." The issue hasn’t been released yet, but a copy of the magazine cover is already circulating on Twitter.

Several websites, including Pain News Network, have wrongly assumed the quote was attributed to Lady Gaga. We regret the error.

The magazine story focuses on a “career-threatening injury" that Lady Gaga suffered and "why she’ll never ignore joint pain again.” But the article only states that she suffers from synovitis, an inflammation of the joint that can be caused by overuse or injury.

Synovitis is also a common symptom of rheumatoid arthritis (RA), but Lady Gaga never actually says she suffers from the autoimmune disease.

The singer hid her chronic pain from fans and even her own staff until 2013, when she finally had surgery to repair the injured hip.

“I hid my injury until I couldn’t walk,” Lady Gaga told Arthritis Magazine. “I had a tear on the inside of my joint and huge breakage.

“The surgeon told me that if I had done another show, I might have needed a full hip replacement. I would have been out at least a year, maybe longer.”

Lady Gaga has been fairly open about her struggle with chronic pain. Last November, she posted on Instagram two images of herself, trying to ease her pain by getting her shoulder massaged and by sitting in a sauna.

“Having a frustrating day with chronic pain, but I find myself feeling so blessed to have such strong intelligent female doctors. I think about Joanne too and her strength and the day gets a little easier," she posted.   

“Joanne” is Lady Gaga’s aunt, who died from lupus at the age of 19 before the singer was even born. The posts drew an outpouring of support from her Instagram followers.

“I was so overwhelmed by the empathy, confessions & personal stories of chronic pain in response to my previous post I thought what the hell. Maybe I should just share some of my personal remedies I've acquired over the past five years,” she said.

“When my body goes into a spasm one thing I find really helps is infrared sauna. I've invested in one. They come in a large box form as well as a low coffin-like form and even some like electric blankets! You can also look around your community for a infrared sauna parlor or homeopathic center that has one."

Lady Gaga is apparently coping quite well with her pain. She soared around the stadium during a spectacular halftime show at this year's Super Bowl. According to the magazine, Lady Gaga is planning another concert tour as well as her first movie, a remake of A Star is Born.

9 Lessons From 9 Years of Living with Chronic Pain

By Lana Barhum, Columnist

In September 2008, I was 32 years old, married, with a newborn and a nine year old, when I learned I had fibromyalgia and rheumatoid arthritis. Chronic pain and illness suddenly dominated my world.

That was almost nine years ago and I have learned a lot from this often unfair experience. It seems chronic pain and illness have much to teach us. Here are 9 lessons I’ve learned:

1) I am Stronger than I Ever Imagined

There was a time when I didn’t think I could ever meet the challenges imposed by pain and illness. But you don’t know how strong you are until your world comes crashing down and you are left to deal with the aftermath.

The human spirit and body have a high tolerance for pain.  Just when you think you cannot possibly live with it, you find you can.  I have had some pretty painful experiences – some so bad I wished for death.

But I am still here – alive and well. Because no matter what, I am stronger than this. And guess what? So are you.

2) Acceptance is Vital

I spent the first few years of being sick and in pain living in denial.  That choice took its toll on my physical and emotional health.  It was not until I truly accepted my health challenges that I was able to move past them and focus on having a somewhat normal life.

Acceptance also means you are an active participant in your health.  Take your medications and your doctor's advice, keep moving, and focus on bettering your mental and physical health.

I still have days where acceptance is a struggle, but I choose to remind myself what I am feeling isn't permanent.  

3) Don't Take Life So Seriously

As it turns out, there is more to life than being healthy.  You can still have a good, happy life even though you hurt and feel awful. 

There will be good days, bad ones, and even downright ugly ones. But you can still experience moments of happiness, enjoy life, and have meaningful relationships.  Illness and pain don’t define you or dictate your life.

Even at my sickest, I managed fill my life and my children's lives with joy and laughter.  Focusing on the good stuff, not taking life so seriously, and letting go of what you cannot control keeps you from shedding unnecessary tears.

4) Give Grief a Limit

The grief we often feel from chronic illness comes and goes. Like many of you, I have endured plenty of grief-filled moments.  I have been angry, sad, and even clinically depressed.

Grief is normal and natural, especially when your life is continually dominated by pain, sickness, and losses.  Give yourself permission to be angry about your pain, but don’t let those emotions take on a life of their own.

5) Life Can Be Unfair – Let Go

I know all too well that chronic illness and pain are unfair. If I could I have protected my health, I would have, but I couldn't.  And I couldn’t control the snowball effect that continued for several years after my diagnosis. All of it just simply goes back to life being unfair. It has nothing to do with health challenges.

I am learning to let go of what I wanted my life to be and to just focus on what it is now.  Things just happen – like a permanent injury or a chronic disease – that don’t have an explanation.   You can either focus your energy on dwelling on the unfairness or you can move on, let go and learn.

6) People Sometimes Let Us Down

I used to think chronic pain and illness were the worst things that happened to me, but it turns out they weren't.  Finding out that people don’t stick around when the going gets tough is far worse.

Some of my friends walked away.  My family didn’t understand.  And my marriage ended.  Before I got sick, I loved sharing my life with others.  But now that I am not sick and in pain daily, I don’t. People don’t always get that.  That makes maintaining relationships harder.

These days, I place my focus on creating a positive family life for my children and giving us the best life possible.  I don’t have a lot of time and energy to worry about others who don’t understand.   After all, this is MY life – pain, sickness and all - and I get to decide who is in it and who isn't.

7) This is Your Journey – No One Else's

After nine years, I am finally confident in my ability to manage this roller coaster ride alone.  Yes, I can sometimes rely on others to help and provide support, but at the end of the day, I decide the kind of person this life with pain and illness makes of me.

You may have all the support in the world, but you are the only one who can decide the direction this journey goes. Chronic pain can take so much if you let it.

Choose to make the best experience of this journey even when it hurts, and even it feels like you have got nothing left in you. Trust me when I say, “You have got this.”

8) Let Go of Your Fears

I was once afraid of what my life would become, but here I am nine years later and my fears were nothing but wasted time.  Interestingly, my health challenges took my life in directions I never anticipated and most of them have been good.

Don't miss out on the blessings of the present and future because you are dwelling on the past.  Stop being afraid because you can still have a bright future.

9) Never Give Up on Your Health and Happiness

My life changed the day my doctor said, "You have rheumatoid arthritis and fibromyalgia."  I went from being a healthy young mother to someone with an uncertain future.  I don’t take anything in my life for granted anymore and I treasure each day as the gift it truly is.

And the things that I thought I had to give up on – my dreams, watching my children succeed and grow into amazing human beings, and even finding love again – I was so wrong about.  All these things were possible despite chronic pain and illness. And they continue to be.

Lana Barhum is a freelance medical writer, patient advocate, legal assistant and mother. Having lived with rheumatoid arthritis and fibromyalgia since 2008, Lana uses her experiences to share expert advice on living successfully with chronic illness. She has written for several online health communities, including Alliance Health, Upwell, Mango Health, and The Mighty.

To learn more about Lana, visit 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 represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Common Medical Conditions Linked to Fibromyalgia

By Lana Barhum, Columnist

People with fibromyalgia are more likely than others in the general population to have other chronic conditions. But doctors have yet to figure out why fibromyalgia often coexists with other diseases – what’s known as “comorbidity.”

Fibromyalgia sufferers often have migraines, autoimmune diseases, irritable bowel syndrome, depression, anxiety and sleep disturbances. Having multiple overlapping conditions isn’t easy, and increases physical pain and suffering. 

It is important for all of us with fibromyalgia to learn about these conditions and their symptoms.  Being knowledgeable about them will help us and our medical providers better control our symptoms, pain and overall health. 

Here are several common medical conditions faced by people who also have fibromyalgia:

Migraines:  Research indicates migraine sufferers are more likely to have fibromyalgia. One study from 2011, published in The Journal of Headache and Pain, suggests migraine headaches may even trigger fibromyalgia. Researchers believe preventing migraine headaches could potentially stop or slow down the development of fibromyalgia in some people, or minimize symptoms in fibromyalgia sufferers.

"These results suggest different levels of central sensitization in patients with migraine, fibromyalgia or both conditions and a role for migraine as a triggering factor for FMS. Prevention of headache chronification in migraine patients would thus appear crucial also for preventing the development of fibromyalgia in predisposed individuals or its worsening in co-morbid patients,” Italian researchers reported.

Autoimmune Diseases:  In about 25% of cases, fibromyalgia co-exists with an autoimmune condition, according to the Centers for Disease Control and Prevention.  Two serious autoimmune diseases that may accompany fibromyalgia are rheumatoid arthritis (RA) and lupus. 

Other studies show at least 20% of RA patients also have fibromyalgia, but researchers have yet to understand the connection. The pain of RA can trigger fibromyalgia flares, worsen pain and symptoms, and vice versa. 

In 2016, researchers in the UK tried to determine whether RA patients who also had fibromyalgia had lower levels of joint inflammation.  The results of their study, published in BMC Musculoskeletal Disorders, determined RA patients with fibromyalgia had "widespread soft tissue tenderness but fewer clinically inflamed joints, have higher disease activity scores but may have lower levels of synovial [joint] inflammation."

The researchers suggested that different approaches to treatment may benefit these patients.

"These patients are less likely to respond to escalation of inflammation-suppressing therapy and may be more suitable for other forms of treatment including alternative means of pain control and psychological support,” they wrote.

It is also not uncommon for lupus and fibromyalgia to co-occur.  However, fibromyalgia is no more common in lupus than other autoimmune diseases, according to researchers out of the National Data Bank for Rheumatic Diseases. 

Depression and Anxiety: People with fibromyalgia frequently experience depression and anxiety.

According to a 2011 report published in the journal Pain Research and Treatment, 90% of fibromyalgia patients have depressive symptoms at least once, and 86% of those people may suffer from a major depressive disorder. Depression and fibromyalgia occur at the same time in at least 40% cases -- a connection that researchers are still trying to understand.

The prevalence of anxiety symptoms in fibromyalgia patients ranges from 13% to about 71%,  according to Portuguese researchers. 

Irritable Bowel Syndrome: A majority of fibromyalgia patients – up to 70% - also suffer from irritable bowel syndrome (IBS), a digestive disorder characterized by abdominal pain, cramping, bloating, diarrhea and constipation.

Sleep Disturbances:  Most people with fibromyalgia report problems sleeping.  No matter how long they sleep, theyrarely feel rested. Restless leg syndrome, non-restorative sleep, and sleep apnea are all sleep issues associated with fibromyalgia.

People with fibromyalgia are more likely to have restless leg syndrome (RLS) than others in the general population, according to a study from the American Academy of Sleep Medicine (AASM). RLS is a disorder that causes uncomfortable feelings in the legs and/or the urge to keep moving the legs. The AASM study, published in the Journal of Clinical Sleep Medicine, finds 33% of people with fibromyalgia also have RLS.  

Up to 90% of fibromyalgia patients experience non-restorative sleep, a feeling of not getting refreshing sleep, despite appearing to have slept.

A 2013 study published in Clinical and Experimental Rheumatology reports that 61% of men with fibromyalgia suffer from sleep apnea, as well as 32% of women. Sleep apnea is a serious sleep disorder where breathing is interrupted during sleep.  

Living with Fibromyalgia and Co-Existing Conditions                 

In addition to suffering from fibromyalgia, I also suffer from three co-existing conditions -- rheumatoid arthritis, depression, and anxiety.  Having both RA and fibromyalgia, I have struggled with more severe symptoms, including muscle and joint pain and cognitive issues.  I know dealing with this debilitating pain results in both depression and anxiety, and both have been frequent visitors to my life.   

I am aware of the effect multiple conditions have on my well-being, and work hard at improving my overall health. I know I can still have a good quality of life, despite the many obstacles that fibromyalgia and its multiple co-occurring conditions present. 

There are other conditions linked to fibromyalgia that I have not mentioned, but they are still significant. Understanding how fibromyalgia and these conditions coexist may someday help researchers develop better treatments for fibromyalgia. 

Lana Barhum is a freelance medical writer, patient advocate, legal assistant and mother. Having lived with rheumatoid arthritis and fibromyalgia since 2008, Lana uses her experiences to share expert advice on living successfully with chronic illness. She has written for several online health communities, including Alliance Health, Upwell, Mango Health, and The Mighty.

To learn more about Lana, visit 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 represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Even a Little Exercise Is Better Than None

By Pat Anson, Editor

We often hear from pain sufferers who say they’d like to exercise more, but can’t because their pain levels have left them bedridden or stuck on a couch. Others believe a workout at the gym will only make their pain worse.

But two new studies have found that you don’t need to be a gym rat to get the health benefits from exercise.

You may not even need to stand up!

Federal guidelines suggest a minimum of 150 minutes of exercise a week are needed to promote good cardiovascular health. But researchers at Northwestern University wanted to see if a lesser goal could improve overall health.

They measured the physical activity of 1,600 adults with osteoarthritis in their hips, knees or feet; and found that just 45 minutes of moderate physical activity a week improved their function and reduced pain

"We were interested in seeing what kind of physical activity might be beneficial to promote good function down the road,” said Dorothy Dunlop, a professor of rheumatology and preventive medicine at Northwestern University Feinberg School of Medicine.

“We found moderate-intensity activity rather than light activity, such as pushing a grocery cart, to be more valuable to promote future function."

Using sophisticated accelerometers to monitor movement, the researchers found that participants who engaged in moderate activity, such as brisk walking, for at least 45 minutes a week were 80 percent more likely to improve or sustain high future function.

The findings, published in the journal Arthritis Care & Research., were true for both men and women. The beneficial effects of the exercise were also long term. About a third of participants improved or had high function after two years.

"The federal guidelines are very important because the more you do, the better you'll feel and the greater the health benefits you'll receive," Dunlop said. "But even achieving this less rigorous goal will promote the ability to function and may be a feasible starting point for older adults dealing with discomfort in their joints.”

"Even a little activity is better than none," she added

Chair Yoga Relieves Pain of Osteoarthritis

A second study at Florida Atlantic University found that “chair yoga” is an effective way to reduce pain and improve quality of life in older adults with osteoarthritis.

As the name implies, the Sit-N-Fit Chair Yoga program was developed to help those who cannot stand during exercise or participate in traditional yoga. Chair yoga is practiced sitting in a chair or standing while holding the chair for support.

IMAGE COURTESY OF FLORIDA ATLANTIC UNIVERSITY

In a study of 131 older adults who have osteoarthritis, participants attended 45-minute chair yoga sessions twice a week for 8 weeks.

Researchers measured their pain, pain interference (how it affects one's life), balance, gait speed, fatigue and functional ability; before, during and after the sessions.

Compared to a control group enrolled in a health education program, the chair yoga group showed a greater reduction in pain, pain interference and fatigue during the sessions, as well as an improved gait. The reduction in pain interference lasted for about three months after the chair yoga program was completed.

"The effect of pain on everyday living is most directly captured by pain interference, and our findings demonstrate that chair yoga reduced pain interference in everyday activities," said Ruth McCaffrey, emeritus professor in FAU's College of Nursing and co-author of the study published in the Journal of the American Geriatrics Society.

"The potential impact of this study on public health is high, as this program provides an approach for keeping community-dwelling elders active even when they cannot participate in traditional exercise that challenges their balance," said co-author and principal investigator Patricia Liehr, PhD, a professor in FAU's College of Nursing.

Osteoarthritis is the most common form of arthritis and the leading cause of long-term disability in older adults. It affects about a third of Americans over the age of 65.

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.

Can Running Help Prevent Osteoarthritis?

By Pat Anson, Editor

People suffering from aching muscles and joint pain are often told that exercise is the best remedy. It sounds counter-intuitive, but now there’s evidence that running can actually reduce joint inflammation – at least in the knees.

"It flies in the face of intuition," says Matt Seeley, an associate professor of exercise science at Brigham Young University. "This idea that long-distance running is bad for your knees might be a myth."

Seeley and his colleagues conducted a small study of six healthy men and women who ran on treadmills for 30 minutes. Blood samples and synovial fluid from their knee joints were collected both before and after they ran.

The researchers found that two inflammatory markers in the synovial fluid -- cytokines named GM-CSF and IL-15 -- decreased in concentration in the runners after a treadmill session.  Cytokines are small proteins released by cells that play an important role in pain and inflammation.

"What we now know is that for young, healthy individuals, exercise creates an anti-inflammatory environment that may be beneficial in terms of long-term joint health," said Robert Hyldahl, a BYU assistant professor of exercise science.

image courtesy of Nate Edwards/BYU

The findings, published in the European Journal of Applied Physiology, indicate that running may be chondroprotective, which means exercise may help delay the onset of joint diseases such as osteoarthritis (OA), a disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

“This is the first study to evaluate a wide panel of inflammatory mediators in the knee joints of healthy subjects following running. Our results suggest that running decreases intra-articular inflammation and brings to light a novel potential mechanism for the chondroprotective nature of exercise in non-pathologic knees,” the BYU researchers said.

The researchers now plan to study subjects with previous knee injuries, by conducting similar tests on people who have suffered ACL injuries.

"This study does not indicate that distance runners are any more likely to get osteoarthritis than any other person," Seeley said. "Instead, this study suggests exercise can be a type of medicine."

‘Spicy’ Injection Could Take Sting Out of Foot Pain

By Pat Anson, Editor

The U.S. Food and Drug Administration has given "fast track" designation to an injectable pain reliever containing a synthetic form of capsaicin, the active ingredient that makes chili peppers spicy.

The move speeds the development of CNTX-4975 as a treatment for Morton’s neuroma, a painful nerve disorder of the foot. If clinical trials are successful and CNTX-4975 gains full FDA approval, it would be the first use of capsaicin in an injectable analgesic. Capsaicin is already used in skin patches and topical ointments for temporary pain relief.

“We feel the Fast Track designation is recognition that we are pursuing an unmet need for a serious condition with a novel therapy. CNTX-4975 has the potential to help patients avoid surgery, meaning they can avoid the potential complications and recovery associated with surgery, while still achieving the pain relief they are seeking,” said Jim Campbell, MD., founder and President of Centrexion Therapeutics, which is developing the drug.

“We also believe the FDA is trying to encourage development of novel therapies, like CNTX-4975. As a non-opioid, we believe CNTX-4975 could have a major impact in the treatment of chronic pain.”

Centrexion is also studying CNTX-4975 as a possible treatment for osteoarthritis in both humans and dogs.

Morton’s neuroma involves a thickening of the tissue around a nerve leading to the toes, which causes sharp, burning pain in the foot, especially when walking.

The current standard of treatment is steroid injections or surgery to remove the nerve. The surgery often results in permanent numbness in the toes and a potentially long recovery period. 

There are currently no FDA-approved treatments for Morton's neuroma. The agency’s Fast Track process is designed to speed the review of drugs to fill an unmet medical need.

“CNTX-4975 has the potential to provide a high degree and long duration of pain relief without having to undergo surgery. Additionally, CNTX-4975 is highly selective for the capsaicin receptor, which allows it to selectively inactive the local pain fibers while leaving the rest of the nerve fiber functioning, meaning the patient won’t experience numbness in the area of the injection,” said Campbell in an email to PNN.

CNTX-4975 has a short half-life and is cleared from the body within 24 hours, but Campbell says a single injection provides pain relief that lasts for months.

A recent Phase 2b study of CNTX-4975 showed a statistically significant decrease in pain from Morton’s neuroma over a 12-week period. Centrexion plans to begin a Phase 3 trial in 2017.

The company is expecting results later this year on a Phase 2b trial of CNTX-4975 as a treatment for knee osteoarthritis in humans, as well as a study on pet dogs with canine osteoarthritis.

A recent study found that a skin patch containing capsaicin works better than Lyrica (pregabalin) in treating patients with neuropathic pain. Over half the patients using Qutenza had pain relief after about a week, compared to 36 days for those taking pregabalin.  

Study Shows Potential for Early Diagnosis of Arthritis

By Pat Anson, Editor

A new study by British researchers has demonstrated the potential for an experimental blood test that can diagnose arthritis in its earliest stages. Such a test could lead to earlier treatment of osteoarthritis (OA) and rheumatoid arthritis (RA), years before joint damage and physical symptoms begin.

Researchers at Warwick Medical School recruited 225 people with early or advanced OA, RA or another inflammatory joint disease, along with a control group of healthy volunteers with no joint problems.  Their blood and fluid from affected knee joints were then analyzed with mass spectrometry.

The test found patterns in blood plasma amino acids that were damaged by oxygen, nitrogen and sugar molecules. The damage was highest in the blood samples of patients with OA or RA, and markedly lower in the blood of healthy volunteers -- giving researchers identifiable biomarkers that could be used for an early diagnosis.

“This is a big step forward for early-stage detection of arthritis that will help start treatment early and prevent painful and debilitating disease,” said Naila Rabbani, PhD, of Warwick Medical School. “Damage to proteins in the arthritic joint have been known for many years but this is the first time it has been exploited for early-stage diagnosis.

“For the first time we measured small fragments from damaged proteins that leak from the joint into blood. The combination of changes in oxidised, nitrated and sugar-modified amino acids in blood enabled early stage detection and classification of arthritis – osteoarthritis, rheumatoid arthritis or other self-resolving inflammatory joint disease."

Dr. Naila Rabbani of Warwick Medical School

Rabbani says the blood test could be available to patients within two years. Her study is published online in Arthritis Research and Therapy.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine. The World Health Organization estimates that about 10% of men and 18% of women over age 60 have osteoarthritis. There currently is no diagnostic blood test for osteoarthritis.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

A blood test for RA is already on the market in the United States, Canada, Europe, Japan and Australia. The JOINTstat test looks for a protein that is usually found at high levels in the joints of people with RA.

No Increase in Physical Activity after Hip Replacement

By Pat Anson, Editor

A new study by British researchers has come to the surprising conclusion that physical activity such as walking and climbing stairs does not increase after hip replacement surgery.

Total hip replacement is one of the most common elective procedures. The surgery is usually performed on the elderly to relieve pain from osteoarthritis, which causes a loss of cartilage and joint function.

But in the first systematic review to examine the differences in physical activity both before and after hip replacement, researchers were left questioning the purpose of the surgery.

"The most common reason for a hip replacement is to reduce pain on movement. We expected that the amount of physical activity post-surgery would therefore increase. What we found surprised us," said lead researcher Tom Withers, from the University of East Anglia’s School of Health Sciences.

Withers and his colleagues looked at the physical activity of over 1,000 patients who had hip replacements, analyzing how far and how fast they walked, as well as cycling and climbing stairs.

"We found that there was no clear evidence of a change in physical activity following surgery,” said Withers. "The benefits of regular physical activity following a hip replacement are well known, so this research is important for healthcare professionals because it suggests that patients need to be encouraged to be more physically active."

The research findings are being published in the journal Clinical Rehabilitation.

"The lack of significant difference in physical activity after patients undergo such a common procedure suggests there is a need for further research, including further investigation into how other personal characteristics or pre-existing conditions might also influence the results,” says Toby Smith, a lecturer in physiotherapy in UEA's School of Health Sciences.

"Healthcare professionals and researchers need to better understand this lack of change and how patient's perceptions of physical activity might be modified to increase their engagement in physical activity post-operatively."

Recent studies in the United States have questioned whether many joint replacement surgeries are appropriate. A five year study of 175 knee replacement patients by the National Institutes of Health found that over a third of the surgeries were inappropriate. Many patients had pain and other symptoms that were too mild to justify having their knees replaced.  

About 30 million Americans have osteoarthritis, including a growing number of younger patients, aged 40 to 65. Doctors are often reluctant to perform hip replacement surgery on patients under age 50 because prosthetic joints typically last for less than 20 years. A second surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection and other complications.

Nanoparticles May Help Repair Injured Joints

By Pat Anson, Editor

Injecting an injured joint with nanoparticles – tiny, ultrafine particles so small they are invisible to the naked eye – controls inflammation and may help prevent the development of osteoarthritis, according to a new study.

Researchers at the Washington University School of Medicine in St. Louis found that injecting nanoparticles into the injured joints of laboratory mice reduces inflammation and the destruction of cartilage.

The nanoparticles used are more than 10 times smaller than a red blood cell, which helps them penetrate deeply into tissues.  The nanoparticles carry a peptide derived from a natural protein called melittin that has been modified to enable it to bind to a molecule and interfere with inflammation.

“The nanoparticles are injected directly into the joint, and due to their size, they easily penetrate into the cartilage to enter the injured cells,” said Samuel Wickline, MD, a professor of Biomedical Sciences at Washington University.

“Previously, we’ve delivered nanoparticles through the bloodstream and shown that they inhibit inflammation in a model of rheumatoid arthritis. In this study, they were injected locally into the joint and given a chance to penetrate into the injured cartilage.”

The nanoparticles were injected into the mice soon after an injury to prevent the inflammation and cartilage breakdown that can lead to osteoarthritis.

INFLAMMATORY PROTEIN (GREEN) IN CARTILAGE CELLS. IMAGE COURTESY of UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE

Whether such a strategy will work in humans years after an injury -- when osteoarthritis is established and there is severe cartilage loss -- still needs to be studied. But the findings suggest that the nanoparticles, if given soon after joint injuries occur, could help maintain cartilage and prevent the progression to osteoarthritis.

“I see a lot of patients with osteoarthritis, and there’s really no treatment,” said senior author Christine Pham, MD, an associate professor of medicine. “We try to treat their symptoms, but even when we inject steroids into an arthritic joint, the drug only remains for up to a few hours, and then it’s cleared. These nanoparticles remain in the joint longer and help prevent cartilage degeneration.”

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA, and those numbers are expected to grow as the population ages. Frequently, an osteoarthritis patient has suffered an earlier injury — a torn meniscus or ACL injury in the knee. The body naturally responds to joint injuries with inflammation.

“The inflammatory molecule that we’re targeting not only causes problems after an injury, but it’s also responsible for a great deal of inflammation in advanced cases of osteoarthritis,” said Linda Sandell, PhD, a professor of Orthopaedic Surgery and director of Washington University’s Center for Musculoskeletal Research.

“So we think these nanoparticles may be helpful in patients who already have arthritis, and we’re working to develop experiments to test that idea.”

The study findings are published in the Proceedings of the National Academy of Sciences. The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Heart, Lung, and Blood Institute; and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Amgen Biologic Drug Approved by FDA

By Pat Anson, Editor

A new biologic drug may soon be available for rheumatoid arthritis patients and others who suffer from autoimmune diseases – if they can afford it and if the drug clears a patent challenge.

The Food and Drug Administration has approved Amgen’s Amjevita as a biosimilar to Humira for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis and severe plaque psoriasis. 

“Approval of Amjevita is an exciting accomplishment as it marks a new chapter in Amgen’s story of being a leader in biotechnology. In addition, Amjevita holds the potential to offer patients with chronic inflammatory diseases an additional treatment option,” said Sean Harper, M.D., executive vice president of Research and Development at Amgen.

Amjevita is Amgen’s first approved biosimilar and the fourth to receive regulatory approval in the U.S.

“The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

A biosimilar is nearly identical to an already-approved biological drug and there is no clinically meaningful difference in terms of their safety, purity and potency. Unlike generic drugs, however, biosimilars are not considered interchangeable with their branded counterparts – and are not given the generic label.

Zarxio was the first biosimilar product approved by the FDA as a version of Neupogen. The second was Inflectra, a biosimilar to Remicade. Last month the FDA approved Erelzi as a biosimilar to Enbrel.

Biologic products are generally derived from a living organism and can come from many sources, including humans and animals. They help inhibit the joint damage caused by rheumatoid arthritis, a chronic disease in which the body’s own immune system attacks joint tissues, causing pain, inflammation and bone erosion.

Injectable biologic drugs often work well in controlling RA and other autoimmune diseases, but can lose their effectiveness over time. They are also notoriously expensive, with some of the newer drugs costing $20,000 annually. A study last year found that Medicare patients paid an average of $835 in out-of-pocket costs every month to obtain them.

Last year Humira generated sales of more than $8 billion for drug maker AbbVie. In anticipation of Amjevita being approved by the FDA, AbbVie filed a lawsuit against Amgen last month, alleging that Amjevita infringes on 61 of its patents for Humira.

Because of that pending court case, a spokesperson for Amgen told PNN the company would be unable to provide a launch date for Amjevita or a projected price for the drug.

The most serious side effects of Amjevita are infections and malignancies. The drug will have a "Boxed Warning" to alert healthcare providers and patients about an increased risk of serious infections leading to hospitalization or death. The warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including Humira (adalimumab) products.