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.

Can Viagra Treat Diabetic Neuropathy?

By Pat Anson, Editor

An experimental animal study suggest that sildenafil, an erectile dysfunction drug commonly known by the brand name Viagra, may be effective in relieving symptoms of peripheral neuropathy in men with long-term diabetes. The study is published online in PLOS ONE.

Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients feel pain, tingling or burning sensation in their toes, feet, legs, hands or arms. Nearly 26 million people in the U.S. have diabetes and about half have some form of neuropathy, according to the American Diabetes Association. 

In previous animal studies, researchers at Henry Ford Hospital in Detroit found that sildenafil improved blood supply to the sciatic nerve and relieved symptoms of neuropathy. However, it was not known if this therapeutic effect held true for long-term peripheral neuropathy, because the diabetic mice used in the previous experiments were relatively young - 16 weeks old.

"Generally, young diabetic animals with an early stage of peripheral neuropathy are used to investigate various drug treatments," said Lei Wang, MD, the Henry Ford neuroscientist who led the research. "But patients with diabetes who are enrolled in clinical trials often are older and have advanced peripheral neuropathy.

To mimic clinical trials in which diabetes patients have advanced peripheral neuropathy, Wang and his colleagues chose male mice with type II diabetes that were 36 weeks old, roughly equivalent to middle age in humans.

In one group, 15 diabetic mice were treated with an oral dose of sildenafil/Viagra every day for eight weeks. A control group of 15 age-matched diabetic mice were treated daily with the same amount of saline.

Researchers found after a battery of nerve and function tests on both groups of mice that sildenafil markedly improved sensory function after six weeks of treatment.

“Treatment of diabetic mice at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve,” said Wang. “Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment.

“These findings provide new insights into mechanisms underlying the neurological dysfunction of long term diabetic peripheral neuropathy and may lead to the development of a sildenafil therapy for long term diabetic peripheral neuropathy.”

Since becoming available in 1998, Viagra has been found to relieve several other conditions beside erectile dysfunction, such as jet lag and altitude sickness. Some professional athletes also believe that Viagra enhances their performance by opening their blood vessels and increasing oxygen supply to their muscles.

Imaging for Back Pain Often Doesn't Help Older Adults

By Pat Anson, Editor

Spending thousands of dollars on CT scans or MRI’s is often a waste of time and money for older adults with low back pain, according to a large new study published in JAMA.

Researchers at the University of Washington in Seattle say older adults with lower back pain who had spine imaging within six weeks of visiting a primary care doctor had pain and disability over the following year that was no different than other patients who did not have advanced imaging.

“Among older adults with a new primary care visit for back pain, early imaging was not associated with better one-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain,” said Jeffrey G. Jarvik, MD, a professor of radiology in the UW School of Public Health, who studies the cost effectiveness of treatments for patients with low back pain.

Jarvik and his colleagues studied over 5,200 adults aged 65 or older who had a new primary care visit for back pain at three U.S. health care systems. They followed up with the patients 12 months later, comparing pain and disability for those who received early imaging with those who did not. The imaging included radiographs (X-rays), computed tomography (CT scans) and magnetic resonance imaging (MRI) of the lumbar or thoracic spine.

Among the patients studied, 1,174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on measures of back or leg pain-related disability.

When to image older adults with back pain remains controversial. Some guidelines recommend that older adults undergo early imaging because they are more likely to have serious underlying medical conditions, such as cancer or infections.

The American College of Radiology recommends early imaging with MRI for patients older than 70 with back pain, as well as patients older than 50 with osteoporosis. European guidelines say patients older than 55 with back pain should have imaging.

However, Jarvik says there is no strong evidence to support those guidelines.

“Despite the lack of evidence supporting routine imaging for older adults with back pain, guidelines commonly recommend that older patients with back pain undergo imaging,” he wrote. "Our study results support an alternative position that regardless of age, early imaging should not be performed routinely.”

Jarvik says adverse consequences from early imaging are more likely in older adults because they can lead to unnecessary treatments, including steroids injections and surgery.

Early imaging for lower back pain is not recommended for people at any age, according to the Choosing Wisely campaign, an initiative of the ABIM Foundation to encourage physicians and patients to make better choices about their healthcare treatment.

“Most people with lower-back pain feel better in about a month whether they get an imaging test or not. In fact, those tests can lead to additional procedures that complicate recovery,” Choosing Wisely states on its website.

“A study that looked at 1,800 people with back pain found that those who had imaging tests soon after reporting the problem fared no better and sometimes did worse than people who took simple steps like applying heat, staying active, and taking an OTC pain reliever. Another study found that back-pain sufferers who had an MRI in the first month were eight times more likely to have surgery, and had a five-fold increase in medical expenses.”

According to HealthCareBlueBook.com, an MRI of the lower back can range from $880 to $1,230, and a CT scan from $1,080 to $1,520.

A Pained Life: Is Chronic Pain One Disease or Many?

By Carol Levy, Columnist

When someone asks to join the online chronic pain support group I administer, they are asked what brings them to the group. Most often the reply is along the lines of, "I have fibro, CRPS, neuropathies, migraines, spinal issues, etc." 

The naming is usually long, and sad to read. 

Even after doing this for many years it still surprises me when the reply is a laundry list of diagnoses.

It is silly for me to continue to be taken aback. It is the very rare person who names only one illness. 

There has been a lot of discussion surrounding the issue of childhood trauma and abuse as being a progenitor for chronic pain. I have my arguments with that theory. I also wonder if we lose sight of other possible originators of chronic pain disorders in our, and the research community's, willingness to hop on the “abuse as cause” train. 　

I googled, "Chronic pain patients have multiple chronic pain disorders. Why?" The search came up with a number of websites for treatment, but nothing about research that addresses the question. Is there a biological reason, a chemical cause, or maybe genetic issues that cause a body to develop these combinations of diseases?

Often people with cancer in one part of the body see it metastasize to other areas.  My simplistic understanding is that a cancer cell gets loose and travels, spreading the disease.

Diabetics have the risk of eye and skin complications, kidney disease, neuropathy and other problems as a direct result of the diabetes, even when they have been managing the illness very well. The diabetes itself is the trigger for the body processes that cause the side effects. 

Is there a similar mechanism in chronic pain disorders? Does the presence of one condition set off a process that allows other pain disorders to take root? Does the body lose some of its defenses or ability to fight off other pain disorders? 

I am not a medical person. I have no idea if this is nothing more than the personal woolgathering thoughts of someone who thinks we, as a group, are in desperate need of answers.

We already clamor for more research into treatments for our pain. We need to also send out a clarion call for more research into what causes these disorders. This call needs to include looking outside of the box, maybe seeing chronic pain illnesses as a cluster of ailments rather than individual disorders that are distinct and separate from one another. 

We need researchers who can see past a name, who can look at chronic pain and ask the opposite of the Sesame Street song “One of These Things (Is Not Like The Others).”

All of these things are like the others, but what about these things are all the same?

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

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

Researchers Say Brain Processes Pain Emotionally

By Pat Anson, Editor

Many chronic pain sufferers resent being told their pain is “all in your head” or that they’re being too emotional about their pain.

But tests conducted by German researchers suggest that the human brain begins to shift from sensory to emotional processing of pain after just a few minutes of painful stimuli.

Scientists at Technische Universität München (TUM) in Munich enrolled 41 people in a study to measure brain activity as they were exposed to painful heat stimulation of a hand. Participants wore a cap with 64 electrodes that measured nerve cell activity in the brain throughout the experiment. The electroencephalograms (EEGs) made it possible to pinpoint which nerve cells respond to pain.

Participants were then given painful heat stimuli to the hand for ten minutes, with the intensity of the heat varying throughout the experiment. The test subjects were asked to continuously assess the level of their pain on a scale of one to a hundred with the other hand using a slider.

"We were absolutely amazed by the results. After just a few minutes, the subjective perception of pain changed. For example, the subjects felt changes in pain when the objective stimulus remained unchanged. The sensation of pain became detached from the objective stimulus after just a few minutes," said Markus Ploner, MD, a professor for human pain research at the TUM School of Medicine.

Previous studies have shown that brief pain stimulation is predominantly processed by sensory areas of the brain that process signals from nerves in the skin. However, in the heat experiment with longer-lasting pain, the EEGs showed that emotional areas of the brain became active.

"If pain persists over a prolonged period of time, the associated brain activity shows that it changes from a pure perception process to a more emotional process. This realization is extremely interesting for the diagnosis and treatment of chronic pain where pain persists for months and years," explained Ploner.

A second experiment showed that it is not just the duration, but also the anticipation of pain that affects perception. Twenty test subjects were given different intensities of painful laser pulses on two areas of the back of the hand. The participants then verbally rated how strong they perceived the pain to be.

In a second round of testing, the subjects were again given the same stimuli, but this time with two creams applied to both hand areas. Although neither cream contained an analgesic, the subjects were told that one of the creams had a pain-relieving effect.

Researchers found the cream had a placebo effect.

"The subjects assessed the pain on the skin area with the allegedly pain-relieving cream as significantly lower than on the other area of skin," said Ploner.

In addition to feeling less pain, the EEGs showed that nerve cells triggered a different pattern of brain activity.

"Our results show how differently our brain processes the same pain stimuli. Systematically mapping and better understanding this complex neurological phenomenon of 'pain' in the brain is a big challenge, but is absolutely essential for improving therapeutic options for pain patients," added Ploner.

Counseling and Behavioral Therapy Help Vets in Chronic Pain

By Pat Anson, Editor

An innovative two-step program that combines analgesics with deep breathing, relaxation techniques and counseling significantly reduced pain levels in U.S. military veterans who suffer from chronic pain, according to a new study at a VA Medical Center.

Researchers at the Roudebush VA Medical Center in Indianapolis, the Regenstrief Institute and the Indiana University School of Medicine studied 241 veterans who returned from deployments in Iraq and Afghanistan. Findings from the ESCAPE trial -- short for Evaluation of Stepped Care for Chronic Pain – are being published in JAMA Internal Medicine.

It is a critical health issue among veterans, many of whom had multiple, often lengthy deployments. Many have significant long-term pain. We know that medications alone are only modestly successful in helping them; current pain treatments haven't made much of a dent,” said Matthew Blair, MD, the study’s lead investigator and an associate professor of medicine at Indiana University.

A recent study found that nearly half of the American soldiers deployed to Iraq and Afghanistan return home to the U.S. in chronic pain, and about one in seven were using opioid pain relievers. Although pain is a common condition, researchers say no intervention studies had been conducted on the best ways to treat chronic pain in these veterans.

“The absence of studies is concerning because chronic pain may prove even more disabling in veterans of recent conflicts than in veterans of previous eras owing to the high combat intensity,” said Bair, who served for eight years as a U.S. Army physician.

The veterans in the ESCAPE study suffered from moderate to severe chronic pain in the back, knee, neck or shoulder for at least three months. Veterans with substance or abuse problems were excluded from the study, as were those with suicidal thoughts, active psychosis or schizophrenia.

In the first phase of ESCAPE, patients were given 12 weeks of pain medication, ranging from acetaminophen to opioids. Because analgesics may not relieve pain sufficiently when used alone, the veterans were educated about self-management strategies such as goal setting, problem solving, deep breathing and relaxation techniques. Patients were also encouraged to minimize bed rest, return to normal activities, and perform stretching and strengthening exercises.

Step two involved 12 weeks of cognitive behavioral therapy that included psychological counseling for both pain and depression. Nurse care managers consulted with veterans over the telephone, helping them counter negative thoughts – such as helping them understand that while they may not be able to perform the same physical activities they enjoyed before deployment, a substitute activity like swimming might be achievable and decrease their pain.

Those who received the two-step ESCAPE program saw improvement in their function and a decrease in pain severity and pain interference -- how pain interferes with their mood, physical activity, work, relationships, sleep and enjoyment of life.

“The decrease in pain severity and 30 percent improvement in pain-related disability we achieved in the ESCAPE study are clinically significant, and we found that improvement lasted for at least nine months," said Blair.

Researchers say the ESCAPE program could be duplicated to treat chronic pain at other VA medical centers and other large health care systems outside the VA. However, implementing the program in smaller community settings or in private settings may be challenging.

"This is an important, methodologically rigorous study that underscores the value of psychobehavioral treatment in chronic pain,” said Beth Darnall, PhD, a pain psychologist and author of Less Pain, Fewer Pills. “Cognitive-behavioral therapy and the use of relaxation strategies work exceedingly well within the context of a comprehensive pain management program, and when the techniques are used regularly.”

Darnall recommends the same techniques used in the VA study in her own private practice.

“It’s important for people to know that the results from psychobehavioral skills build over time.  In other words, use them daily and your results will unfold and strengthen over the course of weeks and months,” she wrote in an email to Pain News Network.