Experimental RA Vaccine Shows Promise

By Pat Anson, Editor

Australian researchers have developed an experimental vaccine for rheumatoid arthritis (RA)  that could prevent the disease from developing in high-risk patients who have a genetic predisposition for RA.

In a small Phase I clinical study, researchers say the "Rheumavax" vaccine was safe and effective in suppressing the immune system response that triggers RA -- a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1% of adults worldwide suffer from RA.

"Current therapies only treat the symptoms and slow the progression of the disease,” said Professor Ranjeny Thomas of the University of Queensland Diamantina Institute. “We have designed a vaccine-style treatment or ‘immunotherapy’ specifically for individuals carrying high-risk rheumatoid arthritis genes and specific rheumatoid arthritis antibodies, called anti-CCP."

CCP antibodies are present in about 60% to 70% of people with RA and can be detected years before symptoms appear.

The personalized Rheumavax vaccine is made by taking a sample of each patient's blood and extracting an immune system cell called dendritic cells. Those cells are then challenged with a foreign peptide and an immune system modulator to create a vaccine that is then injected back into the patient.

Researchers say Rheumavax "teaches" the patient’s immune system to ignore a naturally occurring peptide that triggers the production of CCP antibodies that cause inflammation. In the study, 18 patients received a single injection of Rheumavax and one month later showed no signs of inflammation or RA disease flares.

“At this stage, the technique would not be ideal for widespread treatment or prevention of rheumatoid arthritis because it’s costly and time-consuming," said Thomas. “However, the promising results of this trial lay the foundations for the development of a more cost-effective, clinically-practical vaccine technology that could deliver similar outcomes for patients." 

"This research is such an exciting advancement for arthritis sufferers.  To know that someday in the future, hopefully the near future, there may be a treatment that actually treats the cause, not just the symptoms of rheumatoid arthritis, makes me very hopeful," said  Jennifer Martin, a rheumatoid arthritis sufferer and columnist for Pain News Network.  

"I often worry that my son could have inherited this awful illness from me and that one day he will begin to show symptoms.  To think that there may be a treatment that is effective very early on, or even before symptoms arise if they are able to detect the gene is very reassuring."

Professor Thomas says if Rheumavax proves successful treating RA, it could also be applied to other autoimmune diseases, such as Type 1 diabetes.  The study is published in the journal Science Translational Medicine. 

Until the late 1990s, one in three RA patients were permanently disabled within five years of disease onset. Although there are no cures for RA, in recent years there has been significant improvement in treatment, with disease control now possible for many patients who receive biologic drugs.

Poor Sleep Makes Osteoarthritis Worse

By Pat Anson, Editor

A new study is adding to the growing body of evidence linking poor sleep habits to chronic pain.

Researchers at Johns Hopkins University School of Medicine say patients with knee osteoarthritis (OA) who slept poorly had greater central sensitization -- which amplifies the amount of pain they feel. They are also more likely to catastrophize -- a clinical term meaning they were consumed by thoughts about pain.

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 OA.

"Our study is the largest and most comprehensive examination of the relationship between sleep disturbance, catastrophizing and central sensitization in knee OA," said lead author Claudia Campbell, PhD, from the Department of Psychiatry & Behavioral Sciences at Johns Hopkins University School of Medicine. The study is published in Arthritis Care & Research.

The study included 208 participants who were categorized into four groups: OA patients with insomnia, OA patients with normal sleep habits, healthy controls with insomnia, and healthy controls without pain and normal sleep habits. Most of the participants were female.

Results showed that patients with knee OA and insomnia had the greatest degree of central pain sensitization compared to the controls. Researchers also found that patients with poor sleep and high catastrophizing scores reported higher levels of central sensitization -- which was associated with increased  pain.

"While no causal processes may be determined from this study, our data suggest that those with low sleep efficiency and higher catastrophizing have the greatest central sensitization. Understanding the intricate relationship between sleep, central sensitization, and catastrophizing has important clinical implications for treating those with chronic pain conditions such as knee OA," said Campbell.

A recent study in Norway found that getting a good night’s sleep plays a key role in determining how bad your pain levels are doing the day.  Those who had trouble sleeping at least once a week had a 52% lower pain tolerance. The study, which was published in the journal PAIN,  is the first to link insomnia and impaired sleep to reduced pain tolerance in a large, general population sample.  

A previous study in Norway found that women who have trouble sleeping are at greater risk of developing fibromyalgia.

Study Links Painkillers to Homicides

By Pat Anson, Editor

You can add the term “homicidal” to the list of stigmas faced by chronic pain patients.

A new study in the journal World Psychiatry has found that certain drugs that affect the central nervous system – particularly opioid painkillers – significantly increase the risk of committing murder.

The Swedish and Finnish researchers behind the study wanted to know if there was any scientific basis for the claim that anti-depressants and other psychotropic drugs can cause violent behavior. It’s an issue that was debated after massacres committed by young people in schools and other public places in Finland and around the world.

"It has been repeatedly claimed that it was the anti-depressants used by the persons who committed these massacres that triggered their violent behavior. It is possible that the massive publicity around the subject has already affected drug prescription practices," said lead author Jari Tiihonen of the Karolinska Institute in Sweden.

In one of the first studies of its kind, researchers analyzed a database of 959 people convicted of homicide in Finland between 2003 and 2011 to see what medications they were taking before their crimes.  

They found that anti-psychotic medication was not associated with a significantly increased risk of homicide, and there was only a slightly elevated risk for most people taking anti-depressants and benzodiazepines – drugs used to treat anxiety and insomnia.

But the study did find, rather surprisingly, that there was a significantly higher risk of committing a homicide associated with opioid pain medications like oxycodone and tramadol (93% higher) and anti-inflammatory pain relievers such as acetaminophen (206% higher).

The risk was even more elevated for young people. For someone under the age of 26, there was a 223% greater chance of them killing someone if they were taking opioids. Young people taking benzodiazepines had a 95% greater risk.

"Benzodiazepines can weaken impulse control, and earlier research has found that painkillers affect emotional processing. Caution in prescribing benzodiazepines and strong painkillers to people with a history of substance abuse is advisable," Tiihonen concluded.

Although alcohol and other intoxicants were also involved in a majority of the homicides, the researchers said their use did not explain the differences between the drug groups.

In 2007, an 18-year old Finnish high school student named Pekka-Eric Auvinen fatally shot eight people at his school before taking his own life. He had been taking anti-depressants for a year prior to the massacre.

The Citizens Commission on Human Rights UK has a list of several other massacres around the world linked to the use of anti-depressants. Opioids are not mentioned in any of the examples.

New Software Helps Doctors See Kids' Pain Levels

By Pat Anson, Editor

Accurately assessing pain levels in a patient is difficult because pain is so subjective. No one really knows how much pain a patient is in – except the patient.

It gets even harder when the patient is a young child who can’t verbally express their feelings the same way an adult can. For decades doctors have relied on low-tech diagnostic tools like the Wong Baker Pain Scale – a series of sad and smiling faces the child chooses from to help the doctor understand how much pain they are in.

Thankfully, that era may be coming to an end with the development of a high-tech approach at the University of California, San Diego School of Medicine.

Researchers there have demonstrated the validity of new software that measures pediatric pain by recognizing facial patterns in each patient. Their study is published online in the journal Pediatrics.

“The current methods by which we analyze pain in kids are suboptimal,” said senior author Jeannie Huang, MD, a professor in the UC San Diego School of Medicine Department of Pediatrics and a gastroenterologist at Rady Children's Hospital-San Diego.

COURTESY UC SAN DIEGO SCHOOL OF MEDICINE

“In this study, we developed and tested a new instrument, which allowed us to automatically assess pain in children in a clinical setting. We believe this technology, which enables continuous pain monitoring, can lead to better and more timely pain management.”

The researchers used the software to analyze pain-related facial expressions from video taken of 50 youths, ages five to 18 years old, who had laparoscopic appendectomies.

Researchers filmed the patients during three different post-surgery visits: within 24 hours of their appendectomy; one calendar day after the first visit and at a follow-up visit two to four weeks after surgery. Facial video recordings and self-reported pain ratings by each patient, along with pain ratings by parents and nurses were collected.

“The software demonstrated good-to-excellent accuracy in assessing pain conditions,” said Huang. “Overall, this technology performed equivalent to parents and better than nurses. It also showed strong correlations with patient self-reported pain ratings.”

Huang says the software also did not demonstrate bias in pain assessment by ethnicity, race, gender, or age – an important consideration given how subjective current pain scales can be.

Because the software operates in real-time, doctors can be alerted to pain when it occurs instead of during scheduled assessments. The technology could also advocate for children when their parents are not around to notify medical staff about their child's pain level.

Huang said the software needs further study with more children and other types of pain in a clinical setting.

“It still needs to be determined whether such a tool can be easily integrated into clinical workflow and thus add benefit to current clinical pain assessment methods and ultimately treatment paradigms,” she said.

Huang says controlling pain is important, not only for the child's comfort, but also for their recovery since studies have shown that under-treatment of pain is associated with poor surgical outcomes.

Can Oxygen Therapy Treat Fibromyalgia?

By Pat Anson, Editor

Hyperbaric oxygen therapy – also known as HBOT – has been used for decades to treat infections, severe burns, carbon monoxide poisoning, even scuba divers recovering from decompression sickness.

Patients undergoing HBOT are put in a pressurized room or tube. The higher air pressure allows lungs to gather more oxygen than they would normally – helping the body to heal faster.

Promising new research out of Israel suggests that HBOT can also be used to treat fibromyalgia patients by causing neuroplasticity – a “re-wiring” of the brain that can change neural activity in areas overly sensitized by chronic pain. The study has been published in the journal PLoS ONE.

“This study provides evidence that HBOT can improve quality of life and well-being of many FMS (fibromyalgia) patients. It shows for the first time that HBOT can induce neuroplasticity and significantly rectify brain activity in pain related areas of FMS patients,” wrote lead author Shai Afrati, MD, of the Institute of Hyperbaric Medicine, Assaf Harofeh Medical Center.

file photo of a woman getting hyperbaric oxygen therapy

Fibromyalgia is a poorly understood disorder that is characterized by deep tissue pain, headaches, fatigue, depression and insomnia. The cause is unknown and there is no cure.

Afrati, who has also studied oxygen therapy on stroke and concussion victims, enrolled 60 female fibromyalgia patients in his latest study. For five days each week they were given 90 minutes of HBOT with oxygen enriched air.

“It is plausible that increasing oxygen concentration by HBOT can change the brain metabolism and glial function to rectify the FMS-associated brain abnormal activity. It has already been demonstrated that exposure to hyperbaric oxygen induces significant anti-inflammatory effect in different conditions and pathologies,” said Afrati.

After two months, brain imaging showed the women had significant changes in neural activity, and they reported less pain and fewer tender points. Several said that they had either reduced or stopped taking pain medication.

However, not everyone could handle being placed in a pressurized air chamber. Five women dropped out of the study, complaining of dizziness, claustrophobia and an inability to adjust to the air pressure.

But Afrati is encouraged by the results.  

“Follow-up studies are needed in order to investigate the durability of the HBOT effects on FMS. It might be that some patients will need more HBOT sessions,” he wrote. “Since there is currently no solution for FMS patients, and since HBOT is obviously leading to significant improvement, it seems reasonable to let FMS patients benefit from HBOT, if possible, now rather than wait until future studies are completed.”

New Arthritis Treatment Could Slow Joint Damage

By Pat Anson, Editor

Researchers in California are working on a novel method for the treatment of rheumatoid arthritis that could open the door to a new class of medications that prevent joint damage.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. Most RA treatments focus on suppressing the immune system to reduce inflammation and slow progression of the disease.

"Unfortunately, for around 40 percent of patients, immune-targeted therapies are not sufficient to bring them into full remission," said Nunzio Bottini, MD, an associate professor at the La Jolla Institute for Allergy and Immunology and associate professor of Medicine at the University of California, San Diego.

"If we could add a drug that acts on a different target without increasing immune suppression it could be very valuable."

Bottini and his colleagues are focusing on specialized cells called fibroblast-like synoviocytes (FLS) that line the inside of joints, providing lubrication and repairing joint injuries. In RA patients, the cells invade surrounding cartilage and secrete enzymes that break down the rubbery tissue that cushions the bone. They also trigger bone destruction.

"Even if your inflammation is completely under control with the help of current therapies -- and they are excellent -- the damage to the skeletal structure is not necessarily arrested in the long term because synoviocytes continue to cause damage," explains Bottini. "And although synoviocytes are considered the main effectors of cartilage damage in rheumatoid arthritis there's no therapy directed against them."

FLS cells rely on phosphates to transmit signals. When researchers screened tissue samples from rheumatoid arthritis patients for the expression of phosphatases, they discovered that an enzyme called RPTPσ -- short for receptor protein tyrosine phosphatase sigma -- is highly expressed on the surface of their FLS cells. RPTPσ weakens the ability of synoviocytes to aggressively invade the joint's cartilage.

"RPTPσ acts like an inhibitory signal that is pre-coded on the surface of these cells," says postdoctoral researcher Karen Doody, PhD, first author of the study published in Science Translational Medicine.

“Being able to activate RPTPσ's activity gives us a specific tool with which to adjust the migration and aggressiveness of synoviocytes in rheumatoid arthritis," said Doody, who hopes to develop drugs that make the cells less invasive and lose their ability to attach to cartilage.

"The ultimate goal is to use biologics that target synoviocytes in combination with treatments that suppress the immune system, such as methotrexate or anti-TNF, to address all three aspects of rheumatoid arthritis: swollen joints as a result of inflammation, cartilage damage and bone damage."

About 1.5 million Americans and 1% of adults worldwide suffer from RA.

'Robust Response' to National Pain Strategy

By Pat Anson, Editor

Public reaction to the National Pain Strategy has been “very robust” according to the co-chair of the government committee that released a draft version of the report in early April.

Today marks the deadline for public comments on the 72-page report, a long awaited study that calls chronic pain a threat to public health, and identifies several areas where physicians and the healthcare system are failing pain sufferers.

“I think it’s safe to say that there was a very robust response,” said Linda Porter, PhD, co-chair of the National Institutes of Health’s Interagency Pain Research Coordinating Committee (IPRCC).

“I feel  like we really got the word out widely and the comments are coming in from a very broad range of the community, ranging from the professional societies, individual patients, coalitions of patients that have come together, and patient advocacy. So yes, I’m comfortable with it. We’ve gotten a good range of comments from a really broad set of folks.”

Some pain patients and advocates have complained that the IPRCC was dominated by academic researchers, physicians and government bureaucrats – and not enough input was sought from pain sufferers during the drafting of the National Pain Strategy (NPS).

“The NPS is essentially an underpowered, unrealistic, and undemocratic occupational strategy of some pain experts and professionalized lay experts, who were chosen because of their ideology and rank in certain organizations and government,” wrote patient advocate David Becker in his public comment on the NPS.

“There is no evidence that a survey or needs assessment of what Americans want from pain care was done or considered by the NPS and the NPS fails to make a case for their ‘evidence based, high quality, interdisciplinary, integrated multimodal biopsychosocial model’ as being what people in pain actually want out of pain care -- and especially those Americans in pain who will be forced to live with a plan they had no say in developing.”

Porter said she could not release the number of comments that have come in during the public comment period, but she was satisfied patients had a voice in drafting the National Pain Strategy.

“We felt very strongly that their voice had to be heard,” Porter told Pain News Network. “We had patients and patient advocates on every single one of the work groups, on the oversight panel, and on the IPRCC. There was actually a large group of patient advocates and we made sure that each of the working groups had at least a voice on it and some of them had several.”

A list of members on the IPRCC’s oversight committee can be found here. Two of the panel’s 14 members are pain sufferers and/or patient advocates. The rest are longtime experts in the field of pain management, including several who helped write the 2011 Institute of Medicine report, “Relieving Pain in America,” which estimated that 100 million Americans suffer from chronic pain.

Implementing the Plan

One member of the oversight committee said he found it “really exciting in terms of changing the culture of pain,” but admitted there were “minor things” about the NPS that bothered him.

“There is nothing in it about pediatric pain. There’s not as much emphasis on research as we would always like, particularly basic science is left out of it,” said Greg Terman, MD, an anesthesiologist and professor at the University of Washington who is president of the American Pain Society.

“The general problem that I had as a member of the oversight committee is how are we going to implement any of the recommendations? And the answer is I don’t think anyone knows yet, it’s not even final. But I am optimistic.”

The NPS calls for significant improvement in pain management practices, including better education in pain care for physicians, more collaboration between primary care physicians and pain specialists, broader insurance coverage of pain treatments, and more research. But nowhere in the report is the cost for any of the recommendations even discussed.

“That was not our responsibility nor did we have the ability to estimate what these would cost,” says Linda Porter. “It was really out of our scope and we were not asked to do that. It will certainly come up in the planning stage.”

Porter said cost estimates will be handled by the federal Department of Health and Human Services, which is still in the “discussion and planning stage” of deciding which recommendations to implement first. She expects a plan to be announced in late summer or early fall of this year.

“Things move slowly in government I hear,” says Terman. “It’s there, at least in writing, what needs to be done from our expert opinion. Having it gathered all in one area has never been done before and maybe if we can’t make it happen in the next year, maybe in a few more years. If it’s still sitting there waiting to be implemented, sadly there will still be patients waiting to be helped.”

Older Men Less Likely to Be Screened for Osteoporosis

By Pat Anson, Editor

Elderly men are far less likely to be screened for osteoporosis or to take preventive measures against the bone-thinning disease than women, according to the results of a new study.

"We were surprised at how big a difference we found between men and women regarding osteoporosis," said Irina Dashkova, MD, lead author of the study, which is being presented at The American Geriatrics Society's annual meeting in Washington, DC. "In our environment, you just get this perception that osteoporosis is a women's problem. This has to be changed, and the sooner the better.

More than 10 million Americans suffer from osteoporosis, which raises their risk for serious bone fractures.  About 2 million are men -- and another 8 to 13 million men have low bone mineral density, a precursor to osteoporosis. Previous studies have found that 13% of white men over the age og 50 will experience at least one osteoporosis-related fracture during their lifetime.

“We know from research that when men suffer fractures, their mortality is higher than in women and that severe medical consequences and loss of independence are much more prevalent in men,” said Dashkova.

The risk of death after sustaining a hip fracture is twice as high in men compared to women, and loss of independence is also more common in males. Some medical conditions and drugs that can raise the risk of osteoporosis are male-specific, such as prostate cancer drugs that affect the production of testosterone.

Dashkova and her colleagues at North Shore-LIJ Health System surveyed 146 older men and women in New York and Florida and found “stunning” gender differences in attitudes and beliefs about osteoporosis:

• Women were far more likely to report a family history of osteoporosis (nearly 91% compared to 9%)
• Most women would accept osteoporosis screening, while less than 25% of men would
• Women were 4 times more likely to take preventive measures against osteoporosis, such as taking calcium and vitamin D supplements

Part of the problem may be that healthcare providers aren't encouraging men to undergo screening as often as they should.

"Our survey clearly establishes that physicians are just not thinking of screening men. It's only when older men fall and break their hip that someone thinks maybe we should do something to prevent them breaking the other hip," said Gisele Wolf-Klein, MD, director of geriatric education for the North Shore-LIJ Health System. "Not only is society in general unaware of the problem of osteoporosis in men, men are not seeking screening and diagnosis.

"The average age in my practice is in the 90s, and our patients are to be congratulated because clearly they're doing something right. But we have a duty to make sure those later years are as happy and productive as can be and not spent in a wheelchair."

UK Research Could Lead to Blood Test for Fibromyalgia

By Pat Anson, Editor

British researchers have launched a genetic study of fibromyalgia patients that they hope could lead to a new blood test to diagnose the disease.

Fibromyalgia is a poorly understood disorder characterized by deep tissue pain, fatigue, headaches, depression and insomnia. It is notoriously difficult to diagnose and treat, and some doctors refuse to recognize it as a disease.

Scientists at King’s College London will study tissue samples and measurements taken from volunteers enrolled in Twins UK, a comprehensive study on the effects of genes, aging, disease and the environment on over 12,000 identical and non-identical twins.

Four hundreds twins are enrolled in the fibromyalgia study. In each set of twins, one twin suffers from chronic widespread pain, while the other does not. Tissue samples from both twins will be compared to try to identify biomarkers in their DNA associated with chronic pain.

"Our research will help patients in two ways. First it'll contribute to our understanding of how fibromyalgia – and other chronic pain syndromes such as irritable bowel syndrome – develop, and point to pain pathways which we may not have suspected,” said lead researcher Dr. Frances Williams.

"Secondly, we hope it'll lead to identification of a biomarker which we could work into a blood test."

Fibromyalgia is believed to have genetic influences, but researchers say there are many complicated steps between the genes that may contribute to fibromyalgia and the condition itself.

The study will focus on identifying markers in DNA that are associated with the “switching” on or off certain genes. DNA switching is important to health, as it prevents inappropriate processes from occurring in the body when they should not. Identifying those markers could then lead to a blood test.

“As well as enabling the condition to be diagnosed more effectively, it could help to ‘stratify’ patients into groups depending on disease severity, which will help in clinical trials of potential new treatments. It might even help us predict how the condition will progress,” said Williams.

A bioresearch company based in Santa Monica, California is already marketing a blood test that it claims is 99% accurate in diagnosing fibromyalgia.

EpicGenetics introduced the blood test in 2013, calling it the first definitive test for fibromyalgia.

The FM test looks for protein molecules in the blood called chemokines and cytokines, which are produced by white blood cells. Fibromyalgia patients have fewer chemokines and cytokines in their blood, according to the company, and have weaker immune systems than normal patients.

The blood test costs several hundred dollars and results are available in about a week. Critics have said the test is unreliable and the same molecules can be found in people with other disorders, such as rheumatoid arthritis.

Researchers Develop New Painkiller from Lidocaine

By Pat Anson, Editor

A fast acting pain reliever widely used to treat everything from itching to dental pain could be developed into a new medication that offers longer lasting pain relief.

"Because of its versatility and effectiveness at quickly numbing pain in targeted areas, lidocaine has been the gold standard in local anesthetics for more than 50 years," said George Kracke, PhD, an associate professor of anesthesiology and perioperative medicine at the University of Missouri (MU) School of Medicine.

"While lidocaine is effective as a short-term painkiller, its effects wear off quickly. We developed a new compound that can quickly provide longer lasting relief. This type of painkiller could be beneficial in treating sports injuries or in joint replacement procedures."

Lidocaine is used as an injectable pain reliever for minor surgical or dental procedures, and as an over-the-counter ointment or spray to relieve itching, burning and pain from shingles, sunburns, and insect bites.

The new compound -- called boronicaine -- could potentially serve many of those same functions as an injectable or topical painkiller.  

MU researchers synthesized boronicaine as a derivative of lidocaine by changing its chemical structure. They found that boronicaine provided pain relief that lasted five times longer than lidocaine. In pre-clinical, early stage studies, boronicaine provided about 25 minutes of relief, compared to about five minutes of pain relief with lidocaine.

"Although some conditions may warrant the use of a short-lasting painkiller, in many cases a longer lasting anesthetic is a better option," said Kracke, who is lead author of a study published in the chemistry journal ChemMedChem . "Having a longer lasting anesthetic reduces the dosage or number of doses needed, limiting the potential for adverse side effects."

Other types of short term analgesics provide longer pain relief than lidocaine, but they also have side effects they can cause heart toxicity and gastrointestinal problems. Preliminary findings show no toxicity in single-dose studies of boronicaine, though more studies are needed.

"Boronicaine could have distinct advantages over existing painkilling medications," said M. Frederick Hawthorne, PhD, director of MU's International Institute of Nano and Molecular Medicine and a pioneer in the field of boron chemistry. "We're conducting more research into the side effects of the compound, but in time it could very well become a useful material to use as an anesthetic."

Rheumatoid Arthritis Raises Risk of Heart Attack

By Pat Anson, Editor

Rheumatoid arthritis is a painful, disabling and incurable disease of the joints. But what many RA patients don’t know is that it also significantly raises their risk of a heart attack.

A new study by researchers in Mexico found that one quarter of patients with rheumatoid arthritis and no prior symptoms of heart disease could have a surprise heart attack. Their risk was higher even without cardiovascular risk factors such as smoking and diabetes.

“The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk," said  Adriana Puente, MD, a cardiologist at the National Medical Center in Mexico City.

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% of adults worldwide suffer from RA.

Dr. Puente’s study, which was presented this week at the International Conference of Nuclear Cardiology in Madrid, involved 91 RA patients with no prior symptoms of heart disease. Ninety percent of the patients were women, their average age was 59, and they had similar cardiovascular risk factors as the general population.

Nearly one quarter of the patients (24%) had abnormal Gated SPECT, indicating the presence of ischaemia or infarction – decreased blood flow to the heart which can lead to the death of heart tissue.

"The ischaemia and infarction may be explained by the persistence of the systemic inflammation in rheumatoid arthritis which may cause an accelerated atherosclerosis process,” said Puente.

"The results highlight the importance of conducting diagnostic tests in patients with rheumatoid arthritis to see if they have cardiovascular disease, specifically atherosclerotic coronary artery disease (ischaemia or myocardial infarction) even if they have no symptoms and regardless of whether they have cardiovascular risk factors.”

Puente says patients should be warned that some RA medications, such as corticosteroids and methotrexate, can elevate plasma lipid levels and raise their risk of cardiovascular disease.

"Patients with rheumatoid arthritis should be told that they have an elevated predisposition to heart disease and need pharmacological treatment to diminish the inflammatory process and atherosclerotic complications. They also need advice on how best to control their rheumatoid arthritis and decrease their cardiovascular risk factors,” she said

Many health experts believe the inflammation triggered by RA in the joints may raise inflammation throughout the whole body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease.

But the heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

“Inflammation, regardless of where it comes from, is a risk factor for heart disease,” says rheumatologist Jon T. Giles, MD, assistant professor of medicine at Columbia University School of Medicine. “So it’s not surprising that people with inflammatory arthritis like RA, lupus and psoriatic arthritis have more cardiac events.”

Injectable Gel Could Help Knee Cartilage Heal

By Pat Anson, Editor

With the number of knee replacement surgeries soaring in the United States, researchers at the University of Iowa are working on an injectable gel that could repair damaged cartilage and make many knee surgeries unnecessary.

"We are creating an [injectable, bioactive] hydrogel that can repair cartilage damage, regenerate stronger cartilage, and hopefully delay or eliminate the development of osteoarthritis and eliminate the need for total knee replacement," says Yin Yu, a graduate student at the University of Iowa (UI) whose study is featured in the journal Arthritis and Rheumatology.

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.

About 600,000 knee replacement surgeries are performed annually in the U.S. – about twice the number performed 20 years ago. Recent studies have questioned whether many of the surgeries are appropriate.

UI researchers have previously identified precursor cells in healthy cartilage that can mature into new cartilage tissue – a surprising development given the long-held assumption that cartilage is one of the few tissues in the body that cannot repair itself.

The researchers also identified molecular signals that encourage precursor cells to migrate out of healthy tissue and into damaged areas – stimulating the development of new cartilage. One of the signals, called stromal cell-derived factor 1 (SDF1), acts like a “homing beacon” for the precursor cells.

In an experimental model of cartilage injury, Yu loaded the hydrogel with SDF1 and injected it into holes punched into the model cartilage. The precursor cells migrated toward the SDF1 infused gel and filled in the injury site. Subsequent application of a growth factor caused the cells to mature into normal cartilage that repaired the injury.

The new tissue is not as strong as normal cartilage, but researchers think it could be strengthened through physical therapy and exercise.

"There's really no cure for osteoarthritis except for total joint replacement, which is not particularly suitable for younger patients because the artificial joints wear out and need to be replaced multiple times," said James Martin, PhD, a UI assistant professor of orthopedics and rehabilitation who leads the research team.

"Our approach aims to leverage the body's own capacity for repair, and what we've shown is that cartilage does have regenerative potential; you just have to manipulate it just right."

UI Researchers are now looking at different ways to include the growth factor in the hydrogel – possibly by using nano-size plasmids that carry genetic instructions for the growth factor or microspheres loaded with the substance.

Yu and Martin plan to start animal trials within a year and, if the results are promising, begin human trials in about five years.

Injections of platelet rich plasma (PRP) into the knee also show promise in the treatment of osteoarthritis, according to a recent study published in The Journal of the American Osteopathic Association (JAOA).

Only a few small clinical trials have been conducted on the effectiveness of PRP therapy. Researchers at the University of Miami Miller School of Medicine analyzed those trials and found that patients with knee osteoarthritis and other musculoskeletal injuries showed significant improvements as long as two years after PRP injections.

The procedure involves withdrawing blood from the patient and then spinning it to produce a high concentration of platelet cells. The plasma is then injected back into the patient at the injury site, speeding up the healing process. Several top athletes, including Kobe Bryant and Peyton Manning, have used a form of PRP therapy to help them recover from injuries.

Better Sleep Means Less Pain

By Pat Anson, Editor

Getting a good night’s sleep plays a key role in determining how bad your pain levels are doing the day, according to a large new study by researchers in Norway.

The study included more than 10,400 adults from an ongoing Norwegian health study. Each participant underwent a standard test of pain sensitivity -- the cold pressor test -- in which they were asked to keep their hand submerged in a cold water bath for 106 seconds.

Only 32% of participants were able to keep their hand in cold water throughout the experiment. Those who suffered from insomnia were more likely to take their hand out early: 42% did so, compared with 31% of those without insomnia.

Pain sensitivity also increased depending on the frequency of insomnia. Those who had trouble sleeping at least once a week had a 52% lower pain tolerance, while those who reported insomnia once a month had a 24% lower tolerance for pain.

"While there is clearly a strong relationship between pain and sleep, such that insomnia increases both the likelihood and severity of clinical pain. It is not clear exactly why this is the case," wrote lead author Børge Sivertsen, PhD, of the Norwegian Institute of Public Health.

The study, which is published in the journal PAIN,  is the first to link insomnia and impaired sleep to reduced pain tolerance in a large, general population sample. The results suggest that psychological factors may contribute to the relationship between sleep problems and pain, but they do not fully explain it.

“We conclude that impaired sleep significantly increases the risk for reduced pain tolerance. As comorbid sleep problems and pain have been linked to elevated disability, the need to improve sleep among chronic pain patients, and vice versa, should be an important agenda for future research,” the study said.

A previous study in Norway found that women who have trouble sleeping are at greater risk of developing fibromyalgia – although it’s not clear if there’s a cause and effect relationship between the two symptoms.

Another study, recently published in PLoS One, found that insomnia – not surprisingly – made chronic pain patients less likely to exercise. Researchers followed 119 chronic pain patients, most of whom suffered low back pain, and found that quality of sleep was the best predictor of physical activity the next day – not mood or pain intensity.

Doctor Defends Use of Urine Drug Tests

By Pat Anson, Editor

A prominent pain doctor is disputing reports that a widely used urine drug test often gives faulty results.

“They are reasonably reliable and highly cost effective for use in a pain management practice. I would strongly recommend the practitioners use this,” said Laxmaiah Manchikanti, MD, chairman and CEO of the American Society of Interventional Pain Physicians.

Dr. LAXMAIAH MANCHIKANTI

Dr. Manchikanti, who is medical director of a pain clinic in Paducah, Kentucky, was the lead author of a study published in the journal Pain Physician in 2011, which looked at the reliability of immunoassay “point-of-care” (POC) tests. The urine tests are inexpensive and give immediate results, and doctors often use them to monitor their patients for opioid or illicit drug use.

“The UDT (urine drug test) with immunoassay in an office setting is appropriate, convenient and cost effective. Compared with laboratory testing for opioids and illicit drugs, immunoassay office testing had high specificity and agreement,” Manchikanti's study found.

Pain News Network recently reported on the results of a second study conducted by Millennium Health, a San Diego-based drug testing laboratory, which found that POC tests were wrong about half the time – frequently giving false positive and false negatives results for drugs like marijuana and oxycodone. The Millennium study advocates the use of chromatography-mass-spectrometry – a more complex laboratory test that costs thousands of dollars – to confirm POC test results.

“Following the advice from companies in reference to numerous expensive tests and also income generating avenues will only lead to time in the slammer and will not improve patient care at all,” said Manchikanti.

“(The) Millennium study is performed by the company which makes a living by testing. The more samples that are sent to them, the better off they are. Further, they are not even a practical setting. From our practice we send approximately only 2% of the samples for confirmation testing. Even then, the patients can’t pay their bills.”

Manchikanti’s study found false negative and false positive rates for POC tests that were far below the rates reported by Millennium.

For example, Millennium’s false positive rate for oxycodone was 41.3 percent. For Manchikanti, it was only 7.7 percent.

Millennium’s false positive rate for marijuana was 21.3 percent. For Manchikanti, it was just 2 percent.

There were discrepancies between the two studies for several other drugs, including methadone, cocaine and methamphetamine.

Millennium Sponsored Both Studies

How could two studies come to such different conclusions?

There were some differences in their design. Urine samples in the Millennium study came from nearly 4,300 patients in addiction treatment clinics, while the urine samples in Manchikanti’s study came from 1,000 patients in pain management programs. Millennium maintains the patients in its study were younger and more likely to be drug users.

Ironically, the laboratory tests for both studies were conducted by Millennium – which collected samples and provided chromatography-mass-spectrometry testing at no cost to Manchikanti. Millennium is identified as the “sponsor” of Manchikanti’s study, but he says the company had “no influence or interference” in his and his three co-authors’ findings.

“We had our agreement in the beginning itself that they will not be involved in any way in writing the manuscript or publishing the results. Consequently, they really did not have much input into the publication. The publication was as it is and without any bias from the industry,” Manchikanti wrote in an email to Pain News Network.

Millennium’s study, which was published last year in the Journal of Opioid Management, had six co-authors. All but one were employees of the company. The lone exception is a pain management doctor who frequently testifies as a legal expert for Millennium in court cases.

A source with broad experience in the drug testing industry told Pain News Network the data in Millennium’s study was “skewed toward exaggeration.”

“It does not surprise me that Millennium would show a high rate of inconsistencies with the POC test. Remember, their business is to sell confirmation testing, so they will skew the way they present data to try to influence the market to do more confirmation testing.  In most cases, that’s how it works in any study conducted or funded by a device or pharmaceutical company,” the source said.

Millennium bristles at the notion that its study was biased.

“Millennium Health strongly disagrees with the characterization… that the study was skewed or biased in any way,” the company said in a statement to Pain News Network.

“The study was accepted and published by a well-respected, peer-reviewed publication. Millennium Research Institute is committed to the highest ethical and research science standards, and we stand by the results of our study. The study was based on random samples from addiction treatment clients. The data clearly indicated that immunoassay, or point-of-care, tests have a high rate of false positives and false negatives when used to screen patients for illicit drug use.

“Millennium is committed to providing data that helps clinicians evaluate the best course of treatment for patients with pain and addiction issues. Millennium Health performs only the tests ordered by clinicians.”

In recent years a growing number of doctors who treat addicts and pain patients have required them to submit to drug tests. The competition between Millennium and other laboratories for this business is intense. According to one estimate, drug testing has grown into a lucrative $4 billion dollar a year industry.

But Manchikanti maintains that a single inexpensive urine test that costs about $20 is often the only one that’s needed.

“If a proper (patient) history is provided which matches with the test, there is no need for further testing,” he said.

Weird Mushroom Could Lead to New Painkillers

By Pat Anson, Editor

A creepy looking parasitic mushroom that lives on caterpillars could help British researchers develop a new class of painkillers to treat osteoarthritis and other chronic pain conditions.

Scientists at the University of Nottingham are exploring the painkilling potential of cordycepin, a compound found in cordyceps mushrooms, which have been used in traditional Chinese medicine for thousands of years.

The mushroom acts as a parasite in the larvae of ghost moths – growing inside the caterpillar until it eventually kills it. The stalk-like mushroom then grows out of the caterpillar’s mummified body.

Food pellets containing the compound were given to rats and mice to see if cordycepin could relieve pain from a joint injury. The results, according to researchers, were startling.

"When we first started investigating this compound it was frankly a bit of a long-shot and there was much skepticism from the scientific community," said Dr. Cornelia de Moor. "But we were stunned by the response from the pilot study, which showed that it was as effective as conventional painkillers in rats.

A CORDYCEPS MUSHROOM (LEFT) EMERGES FROM A DEAD CATERPILLAR

"This study is the first step in a potential drug development for a new class of drugs for osteoarthritis, although there are a number of hurdles we have to go through - necessarily so - before it gets nearer patients. To the best of our knowledge, cordycepin has never been tested as a lead compound for osteoarthritis pain."

Native Tibetan healers have used cordyceps mushrooms as a tonic to treat a wide variety of conditions. They claim it improves energy, appetite, stamina, libido, endurance, and sleeping.

Researchers believe cordycepin blocks the inflammatory process that cause pain in osteoarthritis, but does so in a way that is completely different than painkillers like corticosteroids and non-steroidal-anti-inflammatory drugs (NSAIDs) such as ibuprofen.  Still unclear is whether cordycepin acts on the knee joint or on the nerves that send pain signals from the knee to the spinal cord.

Until clinical trials can be held to test the safety and effectiveness of cordycepin – which could take years – de Moor warns against people experimenting with herbal products containing the cordyceps mushroom.

"The lack of quality control means that cordyceps preparations for sale in Europe rarely contain much cordycepin, and may contain other harmful compounds," said de Moor, who is also investigating cordycepin as a possible treatment for cancer.

"Dr de Moor's research is certainly novel, and we believe may hold promise as a future source of pain relief for people with osteoarthritis. There is currently a massive gap in available, effective, side-effect-free painkillers for the millions of people with arthritis who have to live with their pain every day, so new approaches are very much-needed,"  said Dr. Stephen Simpson, director of research at Arthritis Research UK, which is helping to fund de Moor’s research.

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.