Can Gum Disease Cause Rheumatoid Arthritis?

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

Zebrafish Could Help Repair Human Spinal Cord Injuries

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Scientists Use Light and Sound to Reduce Pain

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

What Grade Should Your State Get for Pain Care?

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

Study Looked at Pain Policy, Not Practice

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

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

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

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

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

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

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

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

Patient Survey Underway

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

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

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

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

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

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

Placebo Effect is All in Our Heads

By Pat Anson, Editor

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

It’s all in their heads.

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

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

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

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

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

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

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

The study findings are being published in PLOS Biology.

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

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

Researchers Discover ‘Brain Signature’ for Fibromyalgia

By Pat Anson, Editor

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

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

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

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

UNIVERSITY OF COLORADO BOULDER

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

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

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

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

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

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

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

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

Wheat Protein Could Worsen Chronic Illness

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

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

The Importance of Participating in Pain Research

By Barby Ingle, Columnist

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

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

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

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

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

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

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

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

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

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

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

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

More information about Barby can be found on her website.

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

Negative Thoughts About Sleep Make Pain Worse

By Pat Anson, Editor

Negative thoughts about pain and not being able to sleep can worsen chronic pain conditions like fibromyalgia, arthritis and back pain, according to British researchers.

“Pain-related sleep beliefs appear to be an integral part of chronic pain patients' insomnia experience,” said Nicole Tang, a psychologist in the Sleep and Pain Laboratory at the University of Warwick. "Thoughts can have a direct and/or indirect impact on our emotion, behaviour and even physiology. The way how we think about sleep and its interaction with pain can influence the way how we cope with pain and manage sleeplessness.”

Tang and her colleagues developed a scale to measure beliefs about sleep and pain in chronic pain patients, along with the quality of their sleep.

The scale was tested on four groups of patients suffering from long-term pain and bad sleeping patterns, and found to be a reliable predictor of future pain and insomnia.

"This scale provides a useful clinical tool to assess and monitor treatment progress during these therapies," said Esther Afolalu, a graduate student and researcher at the University of Warwick. 

university of warwick

"Current psychological treatments for chronic pain have mostly focused on pain management and a lesser emphasis on sleep but there is a recent interest in developing therapies to tackle both pain and sleep problems simultaneously."

Researchers found that people who believe they won't be able to sleep because of their pain are more likely to suffer from insomnia, thus causing more pain. The vicious cycle of pain and sleeping problems was significantly reduced after patients received instructions in cognitive-behavioural therapy (CBT), a form of psychotherapy in which a therapist works with a patient to reduce unhelpful thinking and behavior.

The study, published in the Journal of Clinical Sleep Medicine, is not the first to explore the connection between pain and poor sleep.

A 2015 study published in the journal PAIN linked insomnia and impaired sleep to reduced pain tolerance in a large sample of over 10,000 adults in Norway. 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.

Study Finds Link Between Weather and Chronic Pain

By Pat Anson, Editor

There may be something to the old adage about “feeling under the weather.”

Early results from a smartphone-based weather study in the UK show that rain and lack of sunshine have an impact on how we perceive pain.

Over 9,000 people are participating in The University of Manchester’s Cloudy with a Chance of Pain project,  using a special app to record their daily pain levels.  

The app also captures hourly weather conditions using the phone’s GPS, giving researchers the ability to compare the pain data with real-time local weather.

Researchers reviewed data from participants in three cities – Leeds, Norwich and London – and found that as the number of sunny days increased from February to April, the amount of time participants spent in severe pain decreased.

Conversely, when the weather turned rainy and cloudy in June, the amount of time spent in severe pain increased.

The 18-month study is only half complete and researchers are still looking to recruit as many people as possible who are willing to track their symptoms.

“If you are affected by chronic pain, this is your chance to take do something personally – and easily – to lead to a breakthrough in our understanding of pain,” said lead investigator Will Dixon, a professor of Digital Epidemiology at The University of Manchester’s School of Biological Sciences.

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

A 2014 study in Australia found that low back pain is not associated with temperature, humidity and rain.  A 2013 Dutch study also concluded that weather has no impact on fibromyalgia symptoms in women.

“Once the link is proven, people will have the confidence to plan their activities in accordance with the weather. In addition, understanding how weather influences pain will allow medical researchers to explore new pain interventions and treatments,” says Dixon.

People with arthritis or chronic pain who are interested in joining the Cloudy with a Chance of Pain project – and who have access to a smartphone – can download the app by clicking here. You need to be at least 17 and live in the UK.

Participants are encouraged to record their pain symptoms daily until the project ends in January.  Researchers hope to use data to develop “pain forecasts” based on weather predictions.

Study Finds Link Between Chronic Pain and Anxiety

By Pat Anson, Editor

A new study helps explain why so many chronic pain patients also suffer from anxiety or depression.

Researchers at the University of Vermont discovered that the body releases the same neurotransmitter in response to stress as it does to chronic neuropathic pain. The findings, published in the journal Biological Psychiatry, could lead to the development of a new and safer class of medication that could treat both pain and anxiety.

In studies on laboratory mice, researchers found that pain signals and the PACAP neurotransmitter (pituitary adenylate cyclase activating polypeptide) share the same pathway to the brain - the spino-parabrachiomygdaloid tract - which travels from the spinal cord to the amygdala, where the brain processes emotional behavior.

"Chronic pain and anxiety-related disorders frequently go hand-in-hand," says senior author Victor May, PhD, a professor of neurological sciences at the University of Vermont. "By targeting this regulator and pathway, we have opportunities to block both chronic pain and anxiety disorders."

May and his colleagues found that anxious behavior and pain hypersensitivity were significantly reduced when a PACAP receptor antagonist -- designed to block the release of the neurotransmitter -- was applied.

"This would be a completely different approach to using benzodiazepine and opioids - it's another tool in the arsenal to battle chronic pain and stress-related behavioral disorders," said May, who found in a previous study that PACAP was highly expressed in women exhibiting symptoms of post-traumatic stress disorder (PTSD).

May’s findings are important because anxiety and stress are currently treated with sedatives, benzodiazepines and other central nervous system (CNS) depressants. When taken with opioid pain medication, the combination of the drugs can lead to extreme sleepiness, respiratory depression, coma and death.

Yesterday, the U.S. Food and Drug Administration ordered new “black box” warning labels be put on all medications that contain opioids, benzodiazepines and CNS depressants, warning patients and physicians about the increased risk.

According to a 2015 study, over a third of the patients prescribed opioids for chronic musculoskeletal pain were given a sedative. And patients with a history of psychiatric and substance abuse disorders were even more likely to be co-prescribed opioids and sedatives.

Animal Studies Show Promise for Safer Opioids

By Pat Anson, Editor

Animal studies currently underway could hold the key to developing new opioid therapies that relieve pain without the risk of addiction, overdose and other harmful side effects.

Researchers at Wake Forest Baptist Medical Center in North Carolina have developed a pain killing compound -- called BU08028 – that relieves pain in monkeys without causing physical dependence. BU08028 is similar to buprenorphine, an opioid currently used to treat both pain and addiction.

"Based on our research, this compound has almost zero abuse potential and provides safe and effective pain relief," said Mei-Chuan Ko, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist and lead author of the study published in the Proceedings of the National Academy of Sciences.

"This is a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, non-addictive pain medications."

This study, which was conducted on 12 monkeys, targeted a combination of mu opioid receptors in the brain – the same receptors targeted in humans by existing opioid pain medication.

The Wake Forest researchers examined behavioral, physiological and pharmacologic factors and found that BU08028 blocked pain signals without the side effects of respiratory depression, itching or adverse cardiovascular events. In addition, the study showed pain relief lasted up to 30 hours in the monkeys and repeated administration did not appear to cause physical dependence.

"To our knowledge, this is the only opioid-related analgesic with such a long duration of action in non-human primates," said Ko. “Given the decades-long effort aimed at developing abuse-free opioid analgesics, BU08028 represents a major breakthrough for opioid medicinal chemistry.”

Ko plans further animal studies on related compounds to see if they have the same safety profiles as BU08028. If those studies are successful, he hopes to begin studies on humans with the ultimate goal of getting FDA approval for a new class of opioid medication.

The research is funded by the National Institutes of Health and National Institute on Drug Abuse.

Rat Study Targets Peripheral Nerves

Another animal study is taking a different approach to pain relief – by targeting nerves in peripheral tissue – not the mu opioid receptors in the brain and spinal cord.

In findings published in Cell Reports, researchers at the University of Texas found that targeting delta opioid receptors on sensory neurons in the peripheral tissue of laboratory rats produces fewer side effects and with much lower abuse potential.

"Being able to increase the responsiveness of peripheral opioid receptor systems could lead to a reduction in systemic opioid administration, thereby reducing the incidence of side effects," says senior study author Nathaniel Jeske of the University of Texas Health Science Center at San Antonio.

One complication is that delta opioid receptors in peripheral tissues only become activated in the presence of inflammation. Because it has not been clear how to overcome this need for an inflammation trigger, the development of drugs that target peripheral nerves has been limited.

Jeske and his colleagues discovered a protein called GRK2 that binds to and prevents delta opioid receptors on rat sensory neurons from responding normally to opioids. But when those peripheral nerves were exposed to a natural inflammatory molecule called bradykinin, GRK2 moved away from the delta opioid receptors, setting off a biochemical reaction that restored the functioning of these receptors.

In addition, rats with reduced GRK2 levels in peripheral sensory neurons regained sensitivity to the pain-relieving effects of a drug that activates delta opioid receptors, and without the need for an inflammatory trigger.

The researchers hope to replicate the same findings using human tissues.

"By shedding light on how inflammation activates delta opioid receptors, this research could potentially lead to the development of safer, more effective opioids for the treatment of pain," said Jeske, whose work is funded by the National Institutes of Health.

Do Men Get More Pain Relief From Marijuana?

By Pat Anson, Editor

Experts tell us that women are more likely to experience chronic pain than men, feel pain more intensely, and are more likely to be undertreated for pain than men are.

The gender gap in pain grew a little wider this week with a new study, published in Drug and Alcohol Dependence, which claims women get far less pain relief from smoking marijuana than men do.

"These findings come at a time when more people, including women, are turning to the use of medical cannabis for pain relief," said lead author Ziva Cooper, PhD, associate professor of clinical neurobiology at Columbia University Medical Center. "Preclinical evidence has suggested that the experience of pain relief from cannabis-related products may vary between sexes, but no studies have been done to see if this is true in humans."

Cooper and her colleagues conducted two double-blinded, placebo-controlled studies that looked at the analgesic effects of cannabis in 42 healthy recreational marijuana smokers – half of them men and half women.

All smoked marijuana at least four times a week prior to enrolling in the study. Participants were excluded if they had pain.

After smoking the same amount of cannabis or a placebo, the participants immersed one hand in a cold-water bath until the pain could no longer be tolerated. Following the immersion, the participants answered a short pain questionnaire.

Among those who smoked cannabis, men reported a significant decrease in pain sensitivity and an increase in pain tolerance. But the women who smoked cannabis did not experience a significant decrease in pain sensitivity, although they did report a small increase in pain tolerance shortly after smoking.

No gender differences were found in how intoxicated the participants felt or how much they liked the effect of cannabis.

“These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women,” said Cooper.  “Sex-dependent differences in cannabis’s analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief.”

A marijuana advocate and caregiver for patients in Rhode Island said she was shocked by the study findings.

"This study concerns me that some women will read this and not even try the most magical pain relief out there," said Ellen Lenox Smith, a columnist for Pain News Network. "We have never, in the nine years of growing for myself and as caregivers for patients, ever had a time that this was not successful because of one's sex. We have had equal amounts of men and women and the only person that did not have success was an elderly woman that was not able to follow the directions due to her anxiety of using it. That was due to the stigma from society, not the product."

Do women really respond differently to marijuana or is there a flaw in the study itself?

Previous research has found that women respond differently to the cold water test and have far less tolerance for pain induced by cold water immersion than men.

“Most studies have used some form of the cold pressor test in which subjects immerse their arm or hand in circulating cold water for a defined period of time, and their results support the hypothesis that cold pain sensitivity is more pronounced in females,” researchers reported in a 2009 review of nearly two dozen studies that used the cold water test.  “Based on the present set of studies, it appears that sex differences in cold pain are consistent, particularly for suprathreshold measures such as tolerance and pain ratings.”

The Columbia University study was funded by the U.S. National Institute on Drug Abuse. Ziva Cooper also received salary support from Insys Therapeutics, which is developing cannabis-based drugs.

‘Weird and Cool’ Discovery Could Lead to Safer Opioid

By Pat Anson, Editor

A “weird and cool” discovery by a team of international researchers could lead to the development of a new opioid medication that relieves pain without the risk of abuse and overdose.

In a case of reverse engineering, scientists in the U.S. and Germany deciphered the atomic structure of the brain’s mu-opioid receptor and then designed a drug – called PZM21 – that activates the receptor without the typical side effects of opioids. In experiments on mice, PZM21 did not cause drug-seeking behavior and did not interfere with breathing – the main cause of death in opioid overdoses.

“With traditional forms of drug discovery, you’re locked into a little chemical box,” said Brian Shoichet, PhD, a professor of pharmaceutical chemistry at UC San Francisco’s School of Pharmacy.

“But when you start with the structure of the receptor you want to target, you can throw all those constraints away. You’re empowered to imagine all sorts of things that you couldn’t even think about before.”

Shoichet and colleagues at Stanford University, the University of North Carolina and the Friedrich Alexander University in Erlangen, Germany published their findings in the journal Nature.

"This promising drug candidate was identified through an intensively cross-disciplinary, cross-continental combination of computer-based drug screening, medicinal chemistry, intuition and extensive preclinical testing," said Brian Kobilka, MD, a Nobel Prize winner and professor of molecular and cellular physiology at Stanford. It was Kobilka who first established the molecular structure of the opioid receptor.

Shoichet and his research team conducted roughly four trillion “virtual experiments” on UCSF computers, simulating how millions of different drug candidates could turn and twist in millions of different angles – called “molecular docking” -- to see how they fit into a pocket on the receptor and activate it. They avoided using molecules linked to the respiratory suppression and constipation typical of other opioids.

This led to the development of PZM21, which efficiently blocked pain in mice without producing the constipation and breathing suppression typical of other opioids. PZM21 also appears to dull pain by affecting opioid circuits in the brain only, with little effect on opioid receptors in the spinal cord. No other opioid has that effect, which Shoichet says is “unprecedented, weird and cool.”

The drug also didn’t produce the hyperactivity that other opioids trigger in mice by activating the brain’s dopamine systems. The mice did not display drug-seeking behavior by spending more time in chambers where they had previously received doses of PZM21.

“After we replicated the lab experiments and mouse studies several times, then I became excited about the potential of this new drug,” said Bryan Roth, MD, a professor of pharmacology and medicinal chemistry at University of North Carolina.

Researchers say more work is needed to establish that PZM21 is truly non-addictive, and to confirm that it is safe and effective in humans.

 “We haven’t shown this is truly non-addictive,” Shoichet cautioned. “At this point we’ve just shown that mice don’t appear motivated to seek out the drug.”

Is Chronic Pain a Family Affair?

By Pat Anson, Editor

We can credit – or blame – our parents for many things, including our eye color, hair color, height, weight, personality, even our cravings for certain foods.

And if our parents have chronic pain, we are also more likely to suffer from pain ourselves, according to research recently published in the journal Pain. 

“Offspring of parents with chronic pain are at increased risk for pain and adverse mental and physical health outcomes,” wrote co-authors Amanda Stone of Vanderbilt University and Anna Wilson of Oregon Health & Science University.

"Although the association between chronic pain in parents and offspring has been established, few studies have addressed why or how this relation occurs."

Stone and Wilson developed a “conceptual model” of how chronic pain can be transmitted from parent to child through genes, parenting, stress, and lifestyle choices.

"Such a framework highlights chronic pain as inherently familial and intergenerational, opening up avenues for new models of intervention and prevention that can be family-centered and include at-risk children," they wrote.

The researchers identify five "plausible mechanisms" to explain the transmission of chronic pain from parent to child:

• Genetics. Children of parents with chronic pain might be at increased genetic risk for sensory as well as psychological components of pain. Research suggests that genetic factors account for about half of the risk of chronic pain in adults.
• Early Neurobiological Development. Having a parent with chronic pain may affect the functioning of the nervous system during critical periods of child development. For example, a baby's development might be affected by the mother's stress levels or behavior during and after pregnancy.
• Social Learning. Children may learn "maladaptive pain behaviors" from parents, such as catastrophizing and excessive worrying about pain.
• Parenting and Health Habits. Chronic pain risk could be affected by parenting behaviors linked to adverse child outcomes--for example, permissive parenting or lack of consistency and warmth. The parents' physical activity level and other health habits might also play a role.
• Exposure to Stress. There may be adverse effects from growing up in stressful circumstances related to chronic pain -- for example, financial problems or parents' inability to perform daily tasks.

Other factors that may explain why some children are at greater risk include chronic pain in both parents, the location of the parent's pain, and the children's personal temperament.

"The outlined mechanisms, moderators, and vulnerabilities likely interact over time to influence the development of chronic pain and related outcomes," wrote Stone and Wilson, who hope their model will help guide future research toward developing early prevention and treatment approaches for children at risk of chronic pain.

Poor Fitness Leads to Childhood Pain

Another recent study in Finland found that poor physical fitness and sedentary behavior are linked to pain in children as young as 6-8 years of age.

The Physical Activity and Nutrition in Children (PANIC) study at the University of Eastern Finland analyzed the physical fitness, exercise, hobbies, body fat and various pain conditions in 439 children. Physically unfit children suffered from headaches more frequently than others. High amounts of screen time and other sedentary behavior were also associated with increased prevalence of pain conditions.

“Pain experienced in childhood and adolescence often persists later in life. This is why it is important to prevent chronic pain, recognize the related risk factors and address them early on. Physical fitness in childhood and introducing pause exercises to the hobbies of physically passive children could prevent the development of pain conditions,” the study found.