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.

New 3-D Image of 'Wasabi' Pain Receptor (Video)

By Pat Anson, Editor

The spicy wasabi that gives a kick to the taste buds of sushi lovers may also be helping scientists develop new treatments for chronic pain.

Researchers at UC San Francisco say a protein in the human nervous system called the "wasabi receptor" -- because it helps us taste and smell spicy food -- also acts as a receptor to  pain signals triggered by itching and inflammation.

They've created a 3-D image of wasabi receptor proteins -- officially known as TRPA1 -- which work as gatekeepers in sensory nerve cells. These gates, normally closed, open in response to strong chemical signals and allow ions to pass into the cell's interior, triggering a warning impulse.

"The pain system is there to warn us when we need to avoid things that can cause injury, but also to enhance protective mechanisms," said David Julius, PhD, professor and chair of UCSF's Department of Physiology, and co-senior author of a new study appearing online in the journal Nature.

"We've known that TRPA1 is very important in sensing environmental irritants, inflammatory pain, and itch, and so knowing more about how TRPA1 works is important for understanding basic pain mechanisms. Of course, this information may also help guide the design of new analgesic drugs."

The challenge for scientists is learning how and where the wasabi receptor is activated by chemical compounds. In theory, that would enable them to design a drug to alleviate pain by controlling the action of the ion channel -- in effect, shutting the gate.

Julius and his colleagues were able to capture images of TRPA1 that revealed its structure in three dimensions, including a cleft where an experimental drug molecule sits when it binds to the ion channel.

"A few drugs have been developed that target TRPA1, and in our 3-D structure we can see where one such drug binds," said Julius. "This provides important insight into how this one major class of drugs interacts with TRPA1 and thus how it may work to block channel function."

Researchers used  a new imaging technique called electron cryo-microscopy (cryo-EM) to create an image of TRPA1 at a resolution of about 4 angstroms. By way of comparison, the thickness of a credit card is about 8 million angstroms.

The cryo-EM images of the TRPA1 ion channel are so refined they show it in three different states --closed, open, and partially open--a range that offers a lot of insight into how the channels work.

"Cryo-EM has undergone a 'resolution revolution' that has enabled us to literally see TRP channels in all their glory," said Julius. "We've had some idea what TRPA1 might look like, but there's something elegant and satisfying about obtaining the structure, because seeing really is believing."

Researchers Say Acetaminophen Dulls Emotions

By Pat Anson, Editor

Health experts have been warning for years about the risk of liver damage caused by taking too much acetaminophen.  Now a new study is out that found a previously unknown side effect of the drug: It also dulls emotions.

Acetaminophen -- also known as paracetamol – is the world’s most widely used over-the-counter pain reliever. It is the active ingredient in Tylenol, Excedrin, and hundreds of other pain medications.

Researchers at Ohio State University conducted two studies involving over 80 college students, half of whom took a large dose of 1000 milligrams of acetaminophen and half who took a placebo. They waited 60 minutes for the drug to take effect.

The students then viewed 40 photographs from a database used by researchers to elicit emotional responses. The photographs ranged from the extremely unpleasant (crying, malnourished children) to the neutral (a cow in a field) to the very pleasant (young children playing with cats).

After viewing each photo, participants were asked to rate how positive or negative the photo was on a scale of -5 (extremely negative) to +5 (extremely positive). Then they viewed the same photos again and were asked to rate how emotional they felt, ranging from 0 (little or no emotion) to 10 (extreme amount of emotion).

Results in both studies showed that participants who took acetaminophen rated all photos less extremely than did those who took the placebo. Positive photos were not seen as positively under the influence of acetaminophen and negative photos were not seen as negatively. The same was true of their emotional reactions.

“People who took acetaminophen didn’t feel the same highs or lows as did the people who took placebos,” said Baldwin Way, an assistant professor of psychology at the Ohio State Wexner Medical Center’s Institute for Behavioral Medicine Research.

For example, people who took the placebo rated their emotional response relatively high (average score of 6.76) when they saw jarring photos of the malnourished child or the children with kittens. But people taking acetaminophen didn’t feel as much in either direction, reporting an average emotion level of 5.85 when they saw the same photos.

Neutral photos were rated similarly by all participants, regardless of whether they took the drug or not.

“This means that using Tylenol or similar products might have broader consequences than previously thought,” said Geoffrey Durso, lead author of the study and a doctoral student in social psychology at The Ohio State University.

“Rather than just being a pain reliever, acetaminophen can be seen as an all-purpose emotion reliever.”

Previous research has shown that acetaminophen reduces not only on physical pain, but also psychological pain.

“Most people probably aren’t aware of how their emotions may be impacted when they take acetaminophen,” said Way.

The study is published online in the journal Psychological Science.

Over 50 million people in the U.S. use acetaminophen each week to treat pain and fever. The pain reliever has long been associated with liver injury and allergic reactions such as skin rash. In the U.S. over 50,000 emergency room visits each year are caused by acetaminophen, including 25,000 hospitalizations and 450 deaths.

Two Drug Combo Relieves Neuropathy Pain

By Pat Anson, Editor

British researchers say a combination of two widely used drugs – an antidepressant and an opioid – can significantly relieve pain and other symptoms caused by neuropathy.

In a study published in the journal PAIN, researchers at Queens University say combining the painkiller morphine with the antidepressant nortriptyline relieved chronic neuropathic pain in nearly 90 percent of patients – significantly better than when either drug is used alone.

"Morphine and nortriptyline are excellent candidates for pain management because of the extensive research conducted on them, their low cost, and widespread availability all over the world," said Ian Gilron, MD, a professor in Queen's School of Medicine and anesthesiologist at Kingston General Hospital.

"Current neuropathic pain treatments are ineffective or intolerable for many sufferers so this new evidence supporting the morphine-nortriptyline combination is important news for patients."

Nortriptyline, an antidepressant sold under the brand names Aventyl and Pamelor, is already being used to treat pain in the arms and legs caused by multiple sclerosis. Morphine has long been used to treat both acute and chronic pain.

Neuropathic pain is characterized by tingling or burning sensations that develop as result of nerve damage caused by conditions such as shingles, diabetes, amputation, inflammation, and cancer. About 8% of adults worldwide suffer from neuropathy. Many drugs used to treat neuropathic pain, such as Neurontin and Lyrica, often don’t work or have unpleasant side effects.

In the double-blind, randomized study, 52 neuropathy patients were given a choice of trying every one of three treatments: morphine alone, nortriptyline alone, and a combination of the two drugs over six-week treatment periods. Patients were asked to record their pain levels and side effects during each treatment.

The average daily pain before treatment was 5.6, measured using a rating scale from 0-10. Average daily pain dropped to 2.6 when patients received the two drug combination. Patients taking nortriptyline and morphine alone rated their pain at 3.1 and 3.4, respectively.

Researchers said that common side effects for both drugs, which include constipation and dry mouth, did not worsen with the combined treatment.

"It's important to remember that we don't want to completely eliminate patients' ability to sense pain as it's a warning system for us, but we do want to find the right balance of pain relief and drug side effects," said Gilron

Nortriptyline and morphine are currently not available in a combined formulation. According to the Mayo Clinic, using the two drugs together is usually not recommended because they both cause sedation.

'National Pain Strategy' Report Released

By Pat Anson, Editor

The National Institutes of Health has quietly released a draft copy of its National Pain Strategy, a long awaited report designed to advance pain research, healthcare and education in the U.S.

The report calls chronic pain a “complex disease and a threat to public health” and identifies several areas where physicians and the healthcare system are failing pain sufferers.

“Access to high-quality integrated care based on clinical evidence is hindered by many challenges, including a payment system that does not support optimal care. Pain management often is limited to pharmacological treatment offered by a single primary care practitioner or to procedure-oriented and incentivized specialty care that is not coordinated and not aligned with the best available evidence or expected outcomes,” the report says.

“Even when interdisciplinary care is provided, creating and executing a care plan is often fragmented, with poor communication among clinicians and without consideration of patient preferences. The clinician or team’s choice of therapy may be based on practice experience or on insurance coverage, rather than one informed by a comprehensive pain assessment, clinical evidence or best practices.”

The report only briefly addresses the controversy over the abuse and diversion of opioid painkillers, and how some pain sufferers are being denied pain medication by their doctors and pharmacists.

“The reluctance of many clinicians to prescribe these medications, and patients’ concerns over stigmatization associated with opioids may jeopardize quality pain control in the population. Only a small percentage of practitioners and patients account for the majority of opioid-related risk through abuse of prescribing privileges and inappropriate management of prescriptions,” the report said.

Other key findings of the report:

• People with pain are too often stigmatized in the health care system and in society, which can lead to delayed diagnosis, misdiagnosis, and bias in treatment.
• Significant barriers to pain care exist, especially for populations disproportionately affected by pain.
• Although pain is widespread in the population, research is lacking on the prevalence, impact, and outcomes of most common chronic pain conditions.
• Significant improvements are needed in pain management practices.
• Primary care doctors are not sufficiently trained in pain assessment and treatment.  
• Greater collaboration is needed between primary care doctors and pain specialists.

“I agree that collaboration between primary and pain specialists is helpful in some cases, though I do not believe it is mandatory,” said Celeste Cooper, a retired nurse and patient advocate who reviewed the report.

“To think that a primary physician cannot complete continuing education courses for management of mild to moderate chronic pain is ridiculous. Primary physicians are on the front lines. They will be held accountable for prevention strategies, but they aren’t able to make assessments for treating pain? This seems like tying their hands behind their backs.’

The National Pain Strategy is an outgrowth of the 2011 Institute of Medicine report, “Relieving Pain in America,” which found that 100 million Americans suffer from chronic pain.

One critic of the new report says it lacks vision and will not make pain care better.

 “I think the report reflects that it has been developed by (and for) special interest groups who are not very skilled at planning or project management. This report is ungainly and lacks a real focus -- and so I think people in pain will be wondering what exactly they can expect to be different and better for them,” said patient advocate David Becker in an email to Pain News Network.

“I think it is unethical for special interest groups to assume that any and every individual in pain cannot be cured and should not receive stem cell therapy or other curative/regenerative care. In this regard, it reinforces the received view -- and a self- serving view -- that people in pain should be treated indefinitely by medical care."

While not perfect, Cooper said she was encouraged by the report's recommendations.

"Looking at chronic pain as a public health issue is the right approach in my opinion. It will avail resources that wouldn’t otherwise be accessible. The report is comprehensive, there will be roadblocks in implementing all the suggestions, but hopefully generations to come will benefit. As an educator, I was impressed on seeing short-term to long-term goals. This strategy provides a mechanism for reassessment and revision," Cooper said in an email.

The Interagency Pain Research Coordinating Committee is accepting public comments on the National Pain Strategy until May 20, 2015.

Comments can be emailed to NPSPublicComments@NIH.gov.

Acetaminophen Ineffective for Back Pain

By Pat Anson, Editor

The world’s most widely used over-the-counter pain reliever is ineffective in treating low back pain and provides little benefit to people with osteoarthritis, according to a new study published in the British Medical Journal.

In a systematic review of a dozen research reports (a study of studies), Australian researchers also questioned many of the conventional treatments for back pain and other musculoskeletal conditions.

Acetaminophen -- also known as paracetamol – is the active ingredient in Tylenol, Excedrin, and hundreds of other pain medications. It is often recommended by doctors worldwide for back pain and osteoarthritis.

"Clinicians should carefully weigh benefits and harms when making treatment decisions. Paracetamol is not efficacious and potentially harmful. In this context we cannot justify its continued use for these prevalent diseases,” said Professor David Hunter of the University of Sydney.

The researchers found “high quality” evidence showing that patients taking acetaminophen are at greater risk of liver toxicity and nearly four times more likely to have abnormal results from liver function tests.

"World-wide, paracetamol is the most widely used over-the counter medicine for musculoskeletal conditions so it is important to reconsider treatment recommendations given this new evidence," said lead author, Gustavo Machado of The George Institute and the University of Sydney.

Low back pain is the leading cause of disability worldwide, and osteoarthritis of the hip or knee is the 11th highest contributor to global disability.

"This latest research, the most comprehensive systematic review of its kind, reaffirms this with an even larger, global patient base, and has for the first time also established that the effects of paracetamol for knee and hip osteoarthritis are too small to be of clinical importance." said senior author Manuela Ferreira of the George Institute for Global Health and the University of Sydney.

"We urgently need to take stock of the evidence for common musculoskeletal conditions, a largely under-recognized health priority, and make sure people are receiving appropriate care."

Treatments known to be effective for low back pain include counseling, physical therapy, exercise and psychological therapies such as cognitive behavioral therapy.

Aerobic exercise, strengthening exercise, weight management and anti-inflammatory medicines have been shown to provide benefit for patients with lower limb osteoarthritis.

A recent study published in The Lancet found that acetaminophen had no effect on pain, disability, function, sleep quality, or quality of life for people with low back pain.

Over 50 million people in the U.S. use acetaminophen each week to treat pain and fever. The pain reliever has long been associated with liver injury and allergic reactions such as skin rash. In the U.S. over 50,000 emergency room visits each year are caused by acetaminophen, including 25,000 hospitalizations and 450 deaths.

Study Claims 10% of Pain Patients Addicted to Opioids

By Pat Anson, Editor

Estimating rates of opioid abuse and addiction has never been easy. Dozens of different studies have come to startling different conclusions, and there is even disagreement over the definition of abuse and addiction.

Now a professor at the University of New Mexico is weighing in on the subject -- and his conclusions are likely to stir even more debate.

In a systematic review of 38 research reports (a study of studies) published in the journal PAIN, lead author Kevin Vowles and his colleagues estimate that up to 30 percent of the opioids prescribed for pain are misused and that about 10 percent of pain patients are addicted to them.

They also question whether opioids should be prescribed at all for chronic pain.

“It is not clear whether the risks of opioid use outweigh the potential for benefit. The efficacy of opioids and their suitability for the long-term management of chronic pain still remain very much in question and while this uncertainty in effectiveness is well established, it stands in somewhat stark contrast to the clinical reality of chronic pain treatment, where rates of prescriptions have skyrocketed such that opioids are now among the most frequently prescribed medications,” wrote Vowles.

“We are not certain whether the benefits derived from opioids, which are rather unclear based on the extant literature, compensate for this additional burden to patients and health care systems.”

The researchers noted there was extremely wide variation in the rates of opioid misuse and addiction in the studies they analyzed. Rates of “problematic use” ranged from less than 1% all the way up to 81%.

One study -- a review of 25 research reports – left the barn door wide open by broadly estimating the “prevalence of problematic opioid use behavior” at 0% to 50% of pain patients.

“The vagueness inherent in these definitions, areas of overlap among them, and their sometimes interchangeable use have made it difficult to determine exact rates and types of problematic opioid use,” conceded Vowles.

Exactly what constitutes opioid misuse is also debatable.

Vowles defined misuse as “opioid use contrary to the directed or prescribed pattern of use, regardless of the presence or absence of harm or adverse effects.” Such a definition means a patient who has stopped using a prescribed opioid – even if they no longer have pain – is misusing the medication.

(Several years ago this writer was sent home from the hospital after surgery with a two week supply of Vicodin. Fortunately, the surgery was successful and the pain subsided after a few days. A half empty bottle of Vicodin sat unused in my medicine cabinet for years before I had sense enough to throw it out. Under Vowles’ definition, I had “misused” the Vicodin.)

Studies by some of the nation’s largest drug screening companies consistently show that many Americans don’t take the drugs that are prescribed for them. A large study by Quest Diagnostics found that 60% of Americans failed to take a medication as prescribed by their physicians and that 42% had no drugs in their system. Should they be included in estimates of misuse?

Rates of addiction in the studies analyzed by Vowles also varied greatly – from 0.7% of pain patients up to 34.1%.

An adjusted analysis by Vowles estimated the average rate of addiction at 8% to 12% -- a figure nearly double the estimate of the National Institutes of Health (NIH). According to the NIH, only about 5% of patients taking opioids as directed for a year end up with an addiction problem.

“Misuse, abuse and addiction mean different things to different researchers,” said Lynn Webster, MD, past president of the American Academy of Pain Medicine and vice president of scientific affairs at PRA Health Sciences.

“We must keep in mind that behaviors determine the diagnoses of misuse, abuse and addiction and these behaviors are subjective interpretations. Subjective interpretations are influenced by one's biases and perspective.  Misuse to one researcher can be addiction to another. Unfortunately there has not been a standard interpretation of behaviors and I doubt there ever will be due to personal beliefs about opioids and addiction.”  

While Webster doesn’t take issue with the design of the study – he does dispute the overall conclusion that the risks of opioid abuse outweigh the benefits.  

“It is undoubtedly true that some people should not be prescribed opioids.  But even using their reported averages for abuse and addiction, a majority of people do not abuse or become addicted and therefore shouldn't necessarily be denied treatment particularly if there is no other option,” Webster wrote in an email to Pain News Network. 

Ironically, only one study analyzed by Vowles even looked at the recreational abuse of opioids – perhaps the biggest contributor to the so-called “epidemic” of prescription drug abuse in the U.S.  That study estimated the rate of abuse by pain patients at just 8% -- far below their estimated rates of misuse.

Vowles admits there are several limitations to his study.

“The most obvious is the degree of variability within this literature. In spite of our attempts to minimize the impact of this variability, the range of misuse and addiction was incredibly broad,” he wrote.

“These sources of variability will likely continue to cloud our ability to make precise estimates. There is clearly room here for a series of carefully controlled studies where sources of variability are held constant, or as constant as possible, to more clearly illuminate prevalence rates of problematic opioid use in individuals with chronic pain.”

Knee Osteoarthritis Raises Risk of Early Death

By Pat Anson, Editor

Osteoarthritis is painful no matter where it occurs – in the hip, fingers, elbow or other joints. But osteoarthritis of the knee seems to be particularly troublesome for middle-aged women. 

British researchers say knee osteoarthritis significantly raises the risk of cardiovascular disease and can even lead to early death.

In a study of early mortality in middle-aged women with osteoarthritis, researchers looked at data collected by the Chingford Study, which followed the health over 1,000 British middle-aged women for over two decades.

They found that osteoarthritis of the knee was strongly associated with early overall death and cardiovascular mortality. Women with knee pain and radiographic osteoarthritis had almost two times greater risk of early death and over three-times increased risk of dying from a cardiovascular event, when compared with women without knee pain or osteoarthritis. 

No link was found between hand osteoarthritis and a higher risk of mortality. 

“These findings suggest that any self-reported knee pain in osteoarthritis, as opposed to hand pain, seems to be a crucial factor leading to early cardiovascular mortality and is likely to be linked with decreased mobility. Radiographic osteoarthritis without pain is not affecting long-term mortality. More research is needed to understand how people adapt to knee pain, and how this leads to cardiovascular impairment,” said lead author Stefan Kluzek, PhD, of the Arthritis Research UK Centre of Excellence for Sport, Exercise and Osteoarthritis at the University of Oxford.

Researchers did not examine the reasons for the higher death rate, but an earlier look at data from the Chingford study found that women with knee OA were more likely to have hypertension, raised blood glucose, and moderately raised serum cholesterol.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis is quite common and affects over 250 million people worldwide. 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.

Racial Disparities Found in Joint Replacement Surgery

By Pat Anson, Editor

Black, Hispanic and Medicaid patients are significantly more likely to be readmitted to the hospital after total joint replacement (TJR) surgery, while women are less likely to suffer complications, according to new studies presented at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In one study, researchers analyzed race and ethnic data on nearly 53,000 patients admitted to Connecticut hospitals for TJR from 2008 to 2012. The average patient was 67 years of age, white, female and covered by Medicare.

Patients who were African-American were 62% more likely to be readmitted to the hospital within 30 days of TJR. Hispanic patients were 50% more likely and Medicaid patients were 40% more likely to be readmitted than patients with private insurance.

"Our study shows that black patients who undergo total knee replacement may have poorer outcomes," said lead study author and orthopedic surgeon Courtland Lewis, MD. "After controlling for two key variables implicated in race and ethnic disparities in hospital readmission -- preoperative comorbidities and type of insurance coverage -- black patients still have a 35 percent higher likelihood of all-cause, 30-day readmission compared to white patients.”

Lewis said the disparity with white patients may be due to black patients having less access to primary care and less communication with health care providers.

Racial disparities in health care have long been documented, including that black patients utilize hip and total knee replacement at rates nearly 40 percent less than white patients, despite having higher rates of osteoarthritis—a leading cause of joint deterioration. Total hip and knee replacements are common surgical treatments for late-stage arthritis.

The overall 30-day readmission rate for patients in the study was about 5 percent. The most common reasons for readmission were postoperative infection, inflammatory reaction due to a joint prosthesis, hematoma complications, and dislocation of a prosthetic joint.

A second study looked at nearly 60,000 knee and hip replacements at a hospital in Ontario, Canada. Researchers found that men were 15% likely than women to return to the emergency department within 30 days of TJR surgery – even though women who had the surgery were older and more likely to be frail. Over half the patients in the study were women.

The findings contradict the theory that TJR is underutilized in female patients because they have worse outcomes then men.

"Despite the fact that women have a higher prevalence of advanced hip and knee arthritis, prior research indicates that North American women with arthritis are less likely to receive joint replacement than men," said lead study author Bheeshma Ravi, MD, an orthopaedic surgery resident at the University of Toronto. "One possible explanation is that women are less often offered or accept surgery because their risk of serious complications following surgery is greater than that of men.

"In this study, we found that while overall rates of serious complications were low for both groups, they were lower for women than for men for both hip and knee replacement, particularly the latter" said Dr. Ravi. "Thus, the previously documented sex difference utilization of TJR cannot be explained by differential risks of complications following surgery." 

Men in the study were found to be up 70 percent more likely to have a heart attack within three months of TJR surgery and 70 percent more likely to have an infection or require revision surgery within two years of a total knee replacement.

Depression and Obesity Raise Risk of Low Back Pain

By Pat Anson, Editor

Depression, obesity, smoking, and alcohol use significantly raise the risk of having low back pain, according to a large new study presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

“The results were pretty surprising to us. We kind of expected to find a significant difference but not to that extent,” said lead study author and orthopedic surgeon Scott Shemory, MD.

Shemory and his colleagues at Summa Health and the Crystal Clinic Orthopedic Center in Akron, Ohio reviewed the health records of over 26 million patients from 13 health care systems in the U.S. Of those 26 million patients, 1.2 million were diagnosed with lower back pain.

Researchers then analyzed the records to see if the patients with low back pain had any of the four modifiable risk factors: obesity, depressive disorders, alcohol and tobacco use.

• 19.3% of low back pain patients were depressed
• 16.75% were obese with a body mass index (BMI) over 30
• 16.53% were nicotine dependent.
• 14.66% abused alcohol

The study did not address the “chicken and egg question” of which came first. Do depression and obesity cause low back pain, or does low back pain lead to depression, obesity and other risk factors?

“With our study there was no way to determine the cause and the effect or which came first because there was so much overlap,” Shemory told Pain News Network.

“Especially with alcohol abuse and depressive disorders. Anybody who’s got low back pain for years and years, I don’t think it would be surprising that they would have a higher chance of depression or alcohol abuse.”

Regardless of which came first, Shemory says patients should take steps to improve their health by eliminating risk factors that they can control.

“If a patient has any of these risk factors and has low back pain that doesn’t have a neurogenic cause, like a pinched nerve or something like that, I would be counseling them on trying to control these risk factors, not just for their general health but their back pain and livelihood as well,” he said.

According to the National Instituteof Neurological Disorders and Stroke, about 80 percent of adults experience low back pain at some point in their lives. It is the most common cause of job-related disability and a leading contributor to missed work days. One large survey found that over a quarter of adults reported having low back pain during the past 3 months.

Blood Test Could Detect Early Osteoarthritis

By Pat Anson, Editor

British researchers are close to developing a blood test that would detect osteoarthritis in its early stages, a development that could lead to diagnosis and treatment of the disease years before joint damage occurs.

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.

Researchers at the University of Warwick’s Medical School have identified a biomarker linked to both rheumatoid and osteoarthritis. Diagnostic blood tests already exist for rheumatoid arthritis (RA), but the newly identified biomarker could lead to one which can diagnose both RA and osteoarthritis (OA).

“This is a remarkable and unexpected finding. It could help bring early-stage and appropriate treatment for arthritis which gives the best chance of effective treatment,” said lead researcher  Naila Rabbani, PhD.

“This discovery raises the potential of a blood test that can help diagnose both RA and OA several years before the onset of physical symptoms."

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.

Rabbani’s research focused on citrullinated proteins (CPs), a biomarker suspected to be present in the blood of people with early stage rheumatoid arthritis. It had previously been established that patients with RA have antibodies to CPs, but it was not thought that this was the same for those with OA.

However, the Warwick researchers found for the first time increased CPs levels in both early-stage OA and RA.

They then produced an algorithm of three biomarkers; CPs, anti-CP antibodies, and a bone-derived substance called hydroxyproline.

Using the algorithm the researchers found that with a single test they could potentially detect and discriminate between the two types of arthritis in their early stages, before joint damage has occurred. The test correctly identified 73% of the people with eary OA and 57% of the people with early RA.

“It has been long established that the autoimmunity of early-stage RA leads to antibodies to CPs, but the autoimmunity, and hence antibodies, are absent in early-stage OA. Using this knowledge and applying the algorithm of biomarkers we developed provides the basis to discriminate between these two major types of arthritis at an early stage,” said Rabbani.

“Detection of early stage-OA made the study very promising and we would have been satisfied with this only – but beyond this we also found we could detect and discriminate early-stage RA and other inflammatory joint diseases at the same.

The research is published online in Nature Scientific Reports.