WHO Releases First Guideline for Chronic Low Back Pain

By Pat Anson, PNN Editor

The World Health Organization (WHO) has released its first-ever guideline for managing chronic low back pain, recommending treatments such as exercise, physical therapy, chiropractic care and non-steroidal anti-inflammatory drugs (NSAIDs).

Chronic low back pain — also known as “non-specific low back pain” — is defined as pain that persists longer than three months, with symptoms that cannot be accounted for by a structural spinal problem or disease process such as arthritis.

Although lower back pain (LBP) is the leading cause of disability worldwide – affecting about 619 million people – there has been little certainty about how to treat it. Almost all of the clinical trial evidence reviewed by WHO’s guideline development group was considered low or very low quality, a persistent problem.in many medical guidelines dealing with pain.

The lengthy 274-page guideline takes a dim view of some commonly used therapies for LBP, such as muscle relaxants, anticonvulsants, steroids, opioids, transcutaneous electrical nerve stimulation (TENS), and injectable anesthetics – treatments that are primarily used in high-income countries. WHO recommends a more holistic approach to LBP, using therapies that are affordable and accessible to more people.

"Addressing chronic low back pain requires an integrated, person-centred approach. This means considering each person's unique situation and the factors that might influence their pain experience," Dr. Anshu Banerjee, WHO Director for Maternal, Newborn, Child, Adolescent Health and Ageing, said in a press release. "We are using this guideline as a tool to support a holistic approach to chronic low back pain care and to improve the quality, safety and availability of care."

WHO recommends that adults with chronic LBP start with treatments that are the least invasive and least potentially harmful. The values and preferences of patients should also be considered, as they are more likely to adhere to therapies they consider helpful.  

Recommended Treatments for Chronic LBP

• Patient education and counseling

• Exercise or physical therapy

• Acupuncture or dry needling

• Spinal manipulation (chiropractic care)

• Massage

• Cognitive behavioral therapy or mindfulness

• NSAIDs

• Topical cayenne pepper

The guideline states that opioid analgesics “should never be used as a stand-alone treatment” for chronic LBP. When opioids are used alongside other therapies, the lowest dose should be prescribed and only for a short duration, according to WHO.

Recommendations against routine use are also made about many other pharmaceuticals, including antidepressants, anticonvulsants, muscle relaxers, glucocorticoids (steroids), weight loss drugs, and injectable anesthetics such as lidocaine or bupivacaine.  

No recommendations are made about benzodiazepines, cannabis or acetaminophen (paracetamol), primarily due to lack of evidence, but also because of potentially harmful side effects. Cayenne pepper is the only herbal remedy recommended by WHO.

The guideline does not address surgical procedures such as spinal fusions and spinal cord stimulators, or invasive procedures such as epidural injections.

WHO’s 25-member guideline development group included a broad range of clinical experts from around the world. Among them is Roger Chou, MD, a researcher and longtime critic of opioid prescribing who heads the Pacific Northwest Evidence-based Practice Center. Chou is a co-author of the 2016 and 2022 CDC opioid guidelines, and has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group. Chou let his Oregon medical license lapse in 2022.

One of the clinical trials reviewed by WHO’s guideline group is a controversial Australian study – known as the OPAL study -- that found low dose opioids gave little relief to patients with short-term back and neck pain. The OPAL study has been panned by critics because the treatment period only lasted six weeks and used a formulation of oxycodone that would not normally be used in clinical practice. Nevertheless, it’s been cited as evidence that “prolonged opioid use” is ineffective.

In 2021, WHO updated its guideline on the treatment of chronic pain in children, recommending that prescription opioids only be used for children who are dying or seriously ill. An earlier WHO guideline that recommended more pediatric use of opioids was withdrawn in 2019, after two U.S. congressmen accused the United Nation’s health agency of being “corruptly influenced” by opioid manufactures.  

Neuroplasticity: How the Brain ‘Rewires’ Itself

By Hilary Diefenbach, University of Colorado School of Medicine

High-profile sports like football and soccer have brought greater attention in recent years to concussions – the mildest form of traumatic brain injury.

Yet people often do not realize how common concussions are in everyday life, and seldom does the public hear about what happens in the aftermath of concussions – how long the road to recovery can be and what supports healing. Concussions are important to understand, not only for recovery, but also for the insights that the science of recovery can bring to brain health.

I am a speech language pathologist and an instructor in physical medicine and rehabilitation. I specialize in brain injury rehabilitation, with experience ranging from coma recovery to concussion care.

Treating problems tied to head injuries is complex. This is, in part, because it is not possible to directly examine the brain of a living person and because every brain injury is unique. Many aspects of health, both pre- and post-injury, affect recovery. In treating brain injuries, I work to translate this specialized science for each patient and their unique situation.

Brain Injuries Take Many Forms

While people commonly think of athletes when it comes to concussions, sports-related concussions are just one type of mild brain injury seen in health care practice. Concussions can also result from abusive head trauma, blast exposure, car accidents and falls.

The severity of a brain injury is diagnosed based on symptoms, brain imaging and a neurologic exam. Concussions are characterized by a lack of clear tissue damage seen on brain images like an MRI and by the length of time that a person loses consciousness – defined as between zero to 30 minutes.

In addition, a significant portion of concussions may not be identified or formally diagnosed at all. Even if you do not lose consciousness at the time of an injury, you could still have a concussion. Confusion, sensitivity to noise and lights and even changes to sleep and mood are common symptoms. But often, these signs may be misunderstood as signs of stress or shock during traumatic events, such as a car accident. Some people mistakenly assume that if they don’t lose consciousness, they haven’t experienced a concussion.

People who don’t feel that they have returned to normal after a concussion may need further treatment. Many report chronic symptoms that linger beyond the typical three-month recovery – a condition known as post-concussive syndrome. Around 10% of those who suffer a concussion experience post-concussive syndrome, although differences in how this problem is defined and recorded leads to highly variable estimates across studies.

So how does having a concussion affect the brain over time?

The links between concussion and dementias such as chronic traumatic encephalopathy, or, more generally, the relationship between a brain injury early in life and later brain diseases, are not yet clear. This uncertainty should not stop people from finding a path forward and taking strides to support their own brain health.

Brain ‘Detours’

After recovering from a brain injury, patients want to understand how to minimize further risk to their brain, which is all the more important since prior injury puts the brain at greater risk for further injuries.

Researchers and medical providers have learned that after injury the brain can change and “rewire” itself at a cellular level over the life span – a process called neuroplasticity. Brain cells, called neurons, join to form electrical pathways that power activity within the brain.

In addition to other repair processes, neuroplasticity supports damaged brain areas to reconnect injured routes or find “detours” to restore brain function. This means that in recovery, the brain can literally find a new way – or make one – to regain critical abilities.

Neuroplasticity also offers insight into why each brain injury is unique. Following a concussion, therapists focus on detailed evaluations and patient interviews to identify affected areas and to design an intervention.

While the general map of brain regions and their associated functions is standard, individual variability is common. Brain injuries from the same cause of injury, via similar force and intensity of impact and affecting the same location of the brain, can lead to very different symptoms in different people.

While the brain is fully developed by the time people reach their early 20s, neuroplasticity continues well beyond this point. Researchers have seen neuroplastic change during the life span in both the white and gray matter that form brain tissue. The remapping of brain pathways that occurs in late-life injuries, such as a stroke, is one strong piece of evidence to suggest there may be no specific “end date” to the brain’s capacity to restore its internal connections.

Importantly, fuller density of brain cells is thought to create a buffer that is protective against damage due to injury and aging. This extra “bandwidth” is referred to as cognitive reserve. Broadly speaking, higher levels of baseline cognitive reserve have been linked to genetics, educational attainment and health factors.

Neuroplasticity is one process that research shows is critical to maintaining these reserves throughout life.

Building Brain Health

Cognitive reserve is crucial to brain health both before and after a concussion. Studies show that higher levels of cognitive reserve may lessen your risk for prolonged problems after a concussion.

In addition, injuries that occur during childhood and late life may present different challenges in recovery linked to the brain’s cognitive reserves and overall health. For this reason, screening tools for concussion often probe a person’s medical history prior to the event.

Keeping up cognitive reserves likely maintains healthy brain connections that can help us age better. Bilingualism, maintaining an active social life and even going to museums are linked with lower rates of dementia. These studies support that brain activity is good for brain health and it is triggered by many things, including thinking, learning and engaging with the world around us.

Just as there is no one-size-fits-all brain injury, there is also no single path toward brain health.

Advanced brain imaging to detect concussions is not available in standard clinical settings, so clinicians rarely have clear road maps for rehabilitation. But getting optimal sleep, avoiding excessive drinking or other toxic substances and leading a physically and mentally active life are core tenets of brain health.

Finally, the brain does not exist in isolation. Its health is connected to other parts of the body in many ways. Therefore, doctors recommend treating medical conditions that directly affect our brain health and that reduce brain aging, such as high blood pressure,sleep apnea,migraines and even hearing loss.

Brain health is unique to each person, and brain injury treatment depends on your individual lifestyle and health risks. Strategies to treat specific symptoms vary and should be designed with the help of medical specialists. But brain health and cognitive reserve provide a common direction for everyone. Living an active lifestyle – physically, mentally and socially – can drive neuroplasticity and maintain the brain.

Studies of healthy people offer insights into how individual brains are shaped through everyday activities. For instance, research finds that expert musicians have denser sound-processing regions in their brains. The brains of cab drivers have greater development of spatial memory areas. Even military fighter pilots have been shown to have denser tissue in regions connected to strategic thinking.

These startling discoveries teach us that what we do every day truly matters to brain health. For all of these reasons, brain researchers commonly use the phrase “neurons that fire together, wire together” to describe how the brain’s connections change shape associated with repeated patterns of the electrical firing of brain activity.

While many questions remain to be answered, it is well established that the brain can be shaped throughout life. With this knowledge in mind, we can tend to it with greater care.

Hilary Diefenbach, MA, is a licensed Speech Language Pathologist at the Marcus Institute for Brain Health and an Instructor at the University of Colorado School of Medicine. Hilary specializes in brain injury rehabilitation for adults.

This article originally appeared in The Conversation and is republished with permission.

People in Pain Feel More Stigmatized and Lonely

By Pat Anson, PNN Editor

A new global study of people living with pain found that nearly half feel stigmatized and regularly feel lonely. Women, people of color, and the LGBQ+ community are significantly more likely to feel they are treated differently, not believed, or discriminated against because of their pain.

The consumer health company Haleon conducted an online survey of over 18,000 people in 18 countries, including the United States, Canada, Australia and the UK. It’s the fifth time since 2014 the company has conducted such a survey, which forms the basis for the Haleon Pain Index (HPI), which is “designed to give a voice to those experiencing pain.”

The findings from this year’s survey show that attitudes about pain in a post-pandemic world have grown more judgmental and less tolerant, regardless of where people live. Worldwide, 42% of people in pain said they regularly experience loneliness; with serious loneliness felt by 38% of people in mainland China, 33% in Australia and 32% in the UK.

“Everyday pain is a health issue that can easily be dismissed or trivialized. Many don’t realize its effects can be much worse than the symptoms themselves,” said Linda Papadopoulos, PhD, a psychologist and consultant. “The result of loneliness and mental health impact caused by lack of empathy and being treated differently is only worsening. As a society, we need to improve empathy and understanding in a world that is continuing to harden to these issues.”.

The HPI found that people who already experience bias and discrimination are the most affected by hardening views on pain. 

• 58% of women in pain said they were treated differently, not believed or discriminated against, versus 49% of men. Stigmatization was highest among women in India (74%), Saudi Arabia (74%), Brazil (74%), and mainland China (61%). 

• 59% of people of color said they felt stigmatized because of their pain, versus 48% of white people. This trend is highest in Brazil (71%), Poland (64%), USA (64%), and the UK (60%) 

• 44% of people who identify as LGBQ+ fear that others will make assumptions about them and their pain, compared to 32% of heterosexuals. This trend is highest in India (61%), USA (54%), Canada (49%) and Australia (48%). 

The study also found a striking generational gap in the way people in pain are treated, with younger patients often struggling to make their pain known.

Worldwide, 70% of people in their late teens or 20’s (Gen Z) felt stigmatized because of their pain, compared to just 40% of Baby Boomers aged 60 or older. Levels of stigmatization against Gen Z were highest in India (80%), USA (79%) and UK (74%).

Even just talking about pain can be problematic for younger people. 45% of Gen Z respondents said pain was too much of a taboo for them to speak out, compared to 35% of Baby Boomers.   

“While pain is a universal human experience, resulting in loneliness and stigma for many, its impact varies considerably between social groups, with the most marginalized amongst the worst affected. Our ambition is to break down the barriers to achieving better everyday health for everyone – irrespective of age, race, ethnicity, gender, sexual orientation, disability and other factors,” said Lisa Jennings, Head of Haleon’s global over-the-counter products. 

Despite differences in experience, there is broad agreement among people on the need for a more personalized and compassionate view of pain. Over two-thirds of respondents (68%) said more empathy was needed to address bias and prejudice.

Notably, 69% wished that doctors and 62% wished that pharmacists were better trained on how individual pain is for different patients.

How are you treated by your pharmacist? If you are a pain patient in the United States, please take a few minutes to participate in PNN’s survey on drug shortages and opioid prescribing by clicking here.

The Surprising Connection Between Pain and Politics

By Pat Anson, PNN Editor

“I feel your pain. I feel your pain.”

Bill Clinton was mocked by political pundits for saying that to an AIDS activist while running for president in 1992. Whether he was sincere or not, it was a public display of empathy that helped get Clinton elected.

Clinton may have been prescient about a connection between pain and politics. A large new study suggests that pain could have played a surprising role in the 2020 presidential election. Researchers found that liberals with high levels of pain sensitivity were more likely to vote for Donald Trump, while conservatives who were highly sensitive to pain were more likely to vote for Joe Biden.

Huh? I was skeptical. Initially, so was lead researcher Spike W.S. Lee, an associate professor of marketing at the University of Toronto’s Rotman School of Management.     

“We were honestly not expecting to see this kind of cross-aisle effects of pain sensitivity,” Lee said in a news release. “When we first found it, we thought it might be a fluke. That’s why we ran a replication study. We found it again. We ran extended replications and follow-up studies. We kept finding it.”

Lee and his colleagues ran seven different studies involving over 7,000 U.S. participants to see how pain sensitivity affects our moral and political views. Does it heighten them and make us hold more tightly to them? Or does the pain experience make us more sensitive and accepting of what other people believe?

Lee started thinking about that as a research topic during a dental appointment. He is very sensitive to pain, and asked that a freezing procedure be used to numb his mouth before his teeth were cleaned. Lee found himself enjoying the experience so much that he wondered what having no sensitivity to pain would do to someone’s moral compass.

His research found that liberals with higher pain sensitivity were more likely to endorse traditional conservative values such as loyalty and authority; while pain sensitive conservatives showed more support for traditional liberal values such as caring and fairness.   

The pattern continued when participants were asked about their 2020 voting intentions. As the graphic shows below, liberals (blue line) said they were more likely to vote for Trump if they had more pain sensitivity. Similarly, conservatives (red line) were less likely to vote for Trump over Biden if they were more sensitive to pain.

Journal of Personality and Social Psychology

The pattern not only held up for how participants actually voted in the presidential election, it influenced their support for a diverse group of liberal and conservative politicians, such as Kamala Harris, Mike Pence, Mitch McConnell and Bernie Sanders.

Pain sensitivity also significantly changed the way liberals and conservatives thought about hot button issues such as immigration, global warming, unions, the free-market system and Obamacare.

Does that mean pain sensitivity makes people confused about their political views? Not necessarily. Lee says the more likely explanation is that the pain experience gives people more empathy for others and a greater willingness to look at issues from both sides.

In an age of polarized and often heated politics, that’s not a bad thing. Maybe Bill Clinton was on to something.

The study appears in the Journal of Personality and Social Psychology: Attitudes and Social Cognition.

‘Make Peace with Pain’: How Chronic Pain Patients Can Reduce Suicidal Thoughts

By Pat Anson, PNN Editor

Suicide is an important but difficult subject in the pain community, as many people with poorly controlled pain contemplate ways to end it. In a PNN survey of nearly 6,000 pain patients, nearly half said they considered suicide because their pain was poorly treated.

“Without my opioid medicines I will be completely bedridden in never ending agony,” one patient said. “I fear I will be forced into suicide like so many before me because living in never ending unrelieved pain is not a life worth living.”

“I have been severely tapered to a very inadequate level of pain medication and am in so much pain that I am essentially in bed 24/7. I no longer have a life. It is merely an existence and I completely understand why chronic pain patients commit suicide,” said another.

“I was raised to believe suicide was a sin, but I can't say for sure how I'll feel about suicide in a few years if this pain I'm in continues to worsen,” another patient wrote.

Fortunately, most pain sufferers don’t act on those suicidal thoughts, but some lose hope and sink into despair. According to a 2018 estimate, about a quarter of all opioid overdoses are suicides or suicide attempts.

How can pain sufferers avoid suicide ideation? A recent study published in Pain Medicine suggests that pain acceptance – “making peace with pain” – can help reduce suicide risk.

“We know for a fact that when people are in pain — and a lot of pain in particular — it makes them think about killing themselves because they don’t want to be in pain forever,” says lead author Willie Hale, PhD, Assistant Professor of Psychology at University of Texas at San Antonio. “We know there’s a direct relationship here between these two things: The more pain you have, the more you’re going to have in terms of suicidal cognitions.”

Hale and his colleagues surveyed 207 patients with chronic pain, mostly active-duty military, veterans or family members. Respondents were asked about their pain severity, attitudes about suicide, and whether they thought they were a burden to others.

The study is based on the Interpersonal Theory of Suicide, which holds that suicidal thoughts or ideation often begin when individuals feel rejected by others and believe they are a burden. When combined with a reduced fear of death and a suicide “capability,” those thoughts can turn into suicidal behavior.

Hale says when people learn to accept their pain and make peace with it, feelings of burdensomeness and thoughts of suicide diminish. The pain won’t go away, but acceptance will help people push through the pain and participate in activities that make life enjoyable again. More meaningful activity results in more social connectivity -- helping to reduce feelings of rejection and burdensomeness.

“If you can move people from making no peace with their pain to just being a little bit okay with it, that cuts their suicide risk in half, and if you can get them to a high level of pain acceptance, it gets rid of it altogether,” said Hale. “Even if you can’t actually, functionally do anything to make their pain better, if you can just get them to make peace with it, they’re going to be less likely to kill themselves.”

Of course, pain acceptance will not improve access to opioid medication or prevent someone from being tapered to an ineffective dose. The best way to prevent suicide – not examined in this study – is to give patients appropriate pain relief.

“I attempted suicide as the only means of pain relief left available to me,” a person in pain told us. “Not because I was sad or depressed, but because I simply could not live another 10 minutes with no relief in sight.”

Childhood Trauma and Neglect Increase Risk of Headache Disorders

By Pat Anson, PNN Editor

People who experience traumatic events during childhood, such as physical abuse, sexual abuse or neglect, are more likely to have headache disorders as adults, according to a large new study. The research adds to a growing body of evidence linking adverse childhood experiences (ACEs) to headaches and migraines in adults.

“Traumatic events in childhood can have serious health implications later in life,” says lead author Catherine Kreatsoulas, PhD, of Harvard T.H. Chan School of Public Health. “Our meta-analysis confirms that childhood traumatic events are important risk factors for headache disorders in adulthood, including migraine, tension headaches, cluster headaches, and chronic or severe headaches. This is a risk factor that we cannot ignore.”

Kreatsoulas and her colleagues reviewed 28 studies that examined the childhood histories of nearly 155,000 people in 19 countries. Their findings are published Neurology, the medical journal of the American Academy of Neurology.

About a third of the participants (31%) reported at least one traumatic childhood event. Of those, 26% were diagnosed with a primary headache disorder, compared to 12% of participants who said they experienced no childhood trauma. People who had four or more traumatic events during childhood were more than twice as likely to have a headache disorder than those who had one ACE.

Researchers also examined different types of childhood trauma. Events categorized as “threat” traumas included physical abuse, sexual abuse, emotional abuse, witnessing or being threatened with violence, and serious family conflicts.

Events categorized as “deprivation” traumas included childhood neglect, economic adversity, divorce or separation, parental death, alcohol or substance abuse, and living in a household where someone has a mental illness, chronic illness, disability or is incarcerated.

Threat traumas were linked to a 46% increase in headache disorders, while deprivation traumas were linked to a 35% increase in headaches. Among threat traumas, physical and sexual abuse were associated with a 60% increased risk for headaches. Among deprivation traumas, neglect was linked to a nearly three-fold increased risk for headache disorders.

“Threat or deprivation traumas are important and independent risk factors for headache disorders in adulthood,” said Kreatsoulas. “Identifying the specific types of childhood experiences may help guide prevention and treatment strategies for one of the leading disabling disorders worldwide. A comprehensive public health plan and clinical intervention strategies are needed to address these underlying traumatic childhood events.”

Due to the stigma and sensitive nature of childhood trauma, researchers say it’s likely the number of ACE cases is under-reported by adults.

 “Despite this, the robustness of these findings cannot be underappreciated as the studies composing this meta-analysis represent diverse global regions and the findings supersede cultural contexts,” they said.

The research does not prove that ACEs cause headaches -- it only shows an association.

Previous studies have also linked childhood trauma to an increased risk of chronic pain conditions such as fibromyalgia and lupus, as well as mood and sleep problems.

Experimental Fiber Implants Block Nerve Pain with Light

By Pat Anson, PNN Editor

Researchers at the Massachusetts Institute of Technology have developed experimental fiber implants that could potentially be used to deliver pulses of light from inside the body to inhibit nerve pain. Unlike other implants, the hydrogel fibers are flexible and stretch with the body during movement.     

“Current devices used to study nerve disorders are made of stiff materials that constrain movement, so that we can’t really study spinal cord injury and recovery if pain is involved,” said co-author Siyuan Rao, PhD, now an assistant professor of biomedical engineering at the University of Massachusetts at Amherst. “Our fibers can adapt to natural motion and do their work while not limiting the motion of the subject. That can give us more precise information.”

In tests on laboratory mice with genetically modified nerves, researchers used the fiber implants to deliver blue light to the sciatic nerve, which activated the animals’ hind limb muscles.

When pulses of yellow light were used, the light inhibited neuropathic pain in the mice.

For now, MIT engineers see the fibers primarily as a research tool that can help them study the causes and potential treatments of peripheral nerve disorders in animals.

Credit: Sabrina Urbina Villafranca

Neuropathic pain occurs when peripheral nerves are damaged, resulting in tingling, numbness and stinging sensations in the hands and feet. About 20 million Americans suffer from peripheral neuropathy, which can be caused by diabetes, chemotherapy, lupus, HIV, Lyme disease, celiac disease and many other disorders.

“Now, people have a tool to study the diseases related to the peripheral nervous system, in very dynamic, natural, and unconstrained conditions,” said co-author Xinyue Liu, PhD, who is now an assistant professor at Michigan State University. 

The MIT team’s study, recently published in the journal Nature Methods, grew out of a desire to expand the use of optogenetics -- a technique in which nerves are genetically engineered to respond to light. Exposure to specific light waves can either activate or inhibit a nerve, giving scientists a new way to study how nerves work. 

Scientists have used optogenetics in animals to trace nerves involved in a range of brain disorders, including addiction, Parkinson’s disease, and mood and sleep disorders.

Until now, optogenetics has primarily been used in the brain, an organ that lacks pain receptors, which allows for the relatively painless implantation of rigid devices. The MIT team wondered if optogenetics could be expanded to nerves outside the brain to study peripheral nerve pain.  

Because peripheral nerves undergo constant pushing and pulling from adjoining muscles and tissues, they needed more flexible devices that would not constrain movement or cause tissue damage.  

The new optical fibers are made with hydrogel — a rubbery mix of polymers and water – that is soft and flexible. The fiber has two layers; a core and an outer shell that funnel light through the fiber without escaping or scattering. 

When implanted in mice, researchers say the animals were still able to run freely on an exercise wheel. After two months, the fiber was still resistant to fatigue and could transmit light efficiently to trigger muscle contractions. 

“We are focusing on the fiber as a new neuroscience technology,” Liu says. “We hope to help dissect mechanisms underlying pain in the peripheral nervous system. With time, our technology may help identify novel mechanistic therapies for chronic pain and other debilitating conditions such as nerve degeneration or injury.”

Genetic Variations Involved in a Third of CRPS Cases

By Pat Anson, PNN Editor

Chronic Regional Pain Syndrome (CRPS) is one of the worst and most baffling of pain conditions. It usually starts after an injury to an arm or leg, with the skin in the affected area becoming warm, red and painful to touch. Most cases are mild and people recover after a few months, but in rare cases the condition grows worse, resulting in intense nerve pain that can spread and last for years.

Why do some people develop CRPS, while others get better? A small new study in the UK suggests that a genetic variant may be responsible for about a third of CRPS cases.

Researchers at the University of Cambridge took blood samples from 84 patients enrolled in the CRPS-UK Registry to look for variations in certain genes known as single nucleotide polymorphisms, or SNPs for short. Their DNA was compared to a control group of patients with chronic pain from fibromyalgia and low back pain.

Their findings, recently published in the Journal of Medical Genetics, show that an SNP in 4 genes (ANO10, P2RX7, PRKAG1 and SLC12A9) was “more common than expected” in patients with CRPS for at least a year (CRPS-1) than it was in the fibromyalgia/back pain group.

In all, 25 of the 84 patients (30%) with CRPS-1 had the variations in at least 1 of the 4 genes. None of the variations was found in the control group.

Interestingly, men with CRPS were more likely to have the variations (57%) than women (24%), although the sample sizes are so small the discrepancy will need to be confirmed in a larger study. In real life, women are more likely to have CRPS than men.

“This raises the possibility of different mechanisms of disease in males and females in CRPS-1 and that therapeutic responses may also be influenced by sex,” wrote lead author C. Geoffrey Woods, a clinical geneticist at the Cambridge Institute for Medical Research.  “Our data support an underlying genetic predisposition to CRPS-1 in up to a third of cases, with this effect being most prominent in males.”

There may be a biological explanation for the findings, because the ANO10, P2RX7and SLC12A9 genes are found in immune cells of the peripheral nervous system, which becomes inflamed by CRPS.

All 4 genes are also expressed in macrophages — a type of white blood cell involved in the immune response of healthy people. This suggests that variations in those 4 genes may be what triggers CRPS, which is also known as Reflex Sympathetic Dystrophy (RSD).

CRPS/RSD is difficult to treat and there is no known cure. Some patients have found relief through Scrambler therapy and ketamine infusions.

Millions Disabled by Chronic Pain, Anxiety and Depression

By Pat Anson, PNN Editor

About 12 million people in the United States – nearly 5% of the adult population – have chronic pain that is accompanied by anxiety or depression so severe that it limits their ability to work, socialize and complete daily tasks, according to a new study.

The co-occurrence of chronic pain with anxiety and/or depression (A/D) is well known, but little research has been conducted on its prevalence or impact. To see how often the symptoms occur, researchers at the University of Arizona Health Sciences analyzed responses from nearly 32,000 people who participated in the 2019 National Health Interview Survey.

Their findings, published in in the journal PAIN, show that adults with chronic pain are about five times more likely to report anxiety or depression than those without chronic pain. The risk is even higher in adults with “high impact pain” – pain severe enough to limit daily life and work activities -- who are eight times more likely to have A/D.

"The study's findings highlight an underappreciated population and health care need -- the interdependency between mental health and chronic pain," said lead author Jennifer De La Rosa, PhD, director of strategy for the UArizona Health Sciences Comprehensive Pain and Addiction Center.

De La Rosa and her colleagues found that adults with co-occurring symptoms of pain, anxiety and depression had a significantly more disability compared to those with either chronic pain alone or A/D symptoms alone. Nearly 70% reported that their work was limited, about 44% had difficulty doing errands alone, and over half (56%) had problems participating in social activities.

"I was surprised by the magnitude of the effect with functional limitations," said De La Rosa. "Across all domains of functional activity in life, we saw an enormous jump among people who are living with both conditions. These are people who are at a high risk for functional limitation, which will disturb their quality of life."

Like pain, anxiety and depression are difficult to measure and clinicians have to rely on patients self-reporting their symptoms. Making a diagnosis is also difficult because chronic pain and A/D are interconnected neurologically, affecting the same parts of the brain that control cognition and emotional function. Anxiety and depression can heighten the perception of pain and may increase the likelihood of acute, short-term pain becoming chronic.

"When someone is experiencing both chronic pain and anxiety or depression symptoms, achieving positive health outcomes can become more challenging," said senior author Todd Vanderah, PhD, director of the Comprehensive Pain and Addiction Center. "This study gives us another avenue to explore in our continuing effort to find new ways to treat chronic pain."

Researchers say further studies are needed to see if people receiving pain treatment are also getting mental health care, and whether that care is helping with their symptoms.

A recent study found that anxiety, depression and other mood disorders often precede the development of fibromyalgia, irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS).

Chronic Pain Riskier Than Smoking for Heart Attack Survivors

By Pat Anson, PNN Editor

People recovering from a heart attack who have moderate or severe pain are significantly more likely to die -- even when the pain is not associated with heart disease – according to a large new study that highlights the deadly toll that chronic pain can have on health.

“Pain causes significant loss of function and may lead to disability, all of which contribute to major, global public health issues. Research indicates that pain is linked to higher risk of cardiovascular disease and overall death; however, the impact of pain on death after a heart attack has not yet been examined in large studies,” said lead author Linda Vixner, PhD, an associate professor of medical science at Dalarna University in Sweden.

Vixner and her colleagues analyzed 8.5 years of health data for over 18,300 Swedish adults who had a myocardial infarction (MI) – more commonly known as a heart attack. Their findings, published in the Journal of the American Heart Association, show that pain was common a year after the heart attack, with nearly 45% of participants reporting moderate or extreme pain. About two-thirds of them had persistent or long-term pain.

The effect of pain on mortality was even more pronounced than smoking, a well-known risk factor for cardiovascular disease, cancer and other health problems. Heart attack survivors who reported extreme pain were more than twice as likely to die from any cause during the study period, compared to those who had no pain. Those with moderate pain were 35% more likely to die.

Researchers say the study demonstrates that chronic pain is a major risk factor for health providers to consider when treating a patient recovering from a heart attack.

“Pain severity seems to be an important factor, because mortality among patients with chronic pain is higher than in the general population, especially when chronic pain is severe. In addition, we found that patients with extreme pain were less physically active,” they reported.

“Pain and cardiovascular diseases share many lifestyle‐related risk factors and risk factors related to socioeconomic status, which could be one explanation as to why mortality among patients with pain 1 year after MI was significantly higher than mortality in patients without pain. Pharmaceuticals commonly used in pain treatment (both opioids and nonsteroidal anti‐inflammatory agents) are associated with increased cardiovascular risk, which could also be a part of the explanation.”

Previous studies have found that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) significantly raises the risk of a heart attack or stroke. The FDA says people with a history of cardiovascular disease are at the greatest risk. But the risk is also present for those who don't have heart problems.

A 2016 Vanderbilt University study found that long-term opioid users are more likely to die from cardiovascular and respiratory problems than they are from accidental overdoses.

Can Risk Scores Help Predict if Chronic Pain Will Spread?

By Pat Anson, PNN Editor

The term “biopsychosocial” is a bit of a dirty word in the pain community. Many patients feel that studying the biological, psychological and social factors involved in chronic pain trivializes their physical pain by linking it to anxiety, fatigue, trauma and other stressful life experiences – suggesting the pain is “all in your head.”

But researchers at McGill University in Montreal think biopsychosocial risk factors play a key role in determining the severity and spread of chronic pain to other parts of the body. And that could lead to better ways of treating and preventing pain.   

"By identifying common biopsychosocial factors associated with chronic pain, health care professionals could better personalize treatment plans and improve patient outcomes," said co-author Etienne Vachon-Presseau, PhD, Assistant Professor in the Faculty of Dental Medicine and Oral Health Sciences at McGill University.

Using data from the UK Biobank, a large biomedical database in the United Kingdom, McGill researchers analyzed nine years of health data for nearly 50,000 people who reported a common pain condition such as osteoarthritis, migraine, fibromyalgia and spinal disc degeneration. By the end of the study period, nearly half of the participants (44%) reported their pain had spread to more than one body site.

Why did some people develop chronic overlapping pain conditions (COPCs), while others did not?

To find out, the research team dug deeper into the data, using machine learning algorithms to study 99 different physical, psychological, demographic and sociological factors about the participants, such as their education, mental health, substance use, and socioeconomic status.

The study findings, published in Nature Medicine, identified the biggest risk factors associated with COPC: depression/anxiety, insomnia, neuroticism (feeling fed-up), fatigue, stressful life events, and a body mass index (BMI) above 30.

“Our findings suggest that the biopsychosocial model not only shapes pain experience and maintenance, but also predisposes the development of new pain sites, a phenomenon we refer to as the ‘spreading’ of pain sites,” researchers reported. “Furthermore, we found that the pain site co-occurrence was not random, with a strong dependence between proximal pain sites, shown from either acute or chronic pain sites and from correlations between pain intensity ratings. Thus, biopsychosocial risk scores developed for headache will also moderately predict knee pain and vice versa.”

Based on those findings, the McGill team developed a pain risk score that utilizes six simple questions:

Risk of Pain Spreading Screen

1. Do you have difficulty falling asleep at night or do you wake up in the middle of the night?

2. Do you often feel ‘fed-up’?

3. Over the past 2 weeks, how often have you felt tired or had little energy?

4. Have you ever seen a GP or psychiatrist for nerves, anxiety, tension or depression?

5. In the last two years, have you experienced a serious illness, assault, death of a spouse/partner or close relative, separation/divorce, or financial difficulties?

6. Is your BMI over 30?

McGill researchers say their questionnaire will help providers quickly assess the risk of a pain patient developing more severe pain and how the pain might spread across their body.

“Our model predicted chronic pain spreading across multiple body sites in nearly 50,000 out-of-sample individuals,” researchers said. “We showed that high sensitivity and specificity could still be obtained for certain chronic pain conditions using only six questions. The ability to predict chronic pain, particularly COPCs and its severe forms, with minimal effort has the potential to benefit both research and clinical practice.”

Arthritis Pain Varies Widely Across States

By Pat Anson, PNN Editor

People living in West Virginia are three times more likely to have moderate or severe joint pain from arthritis than those in Minnesota, according to a comprehensive new study that highlights how disparities in education and access to social services contribute to chronic pain.

“Very little research has examined the geography of chronic pain, and virtually none has examined the role of state-level policies in shaping pain prevalence,” says co-author Hanna Grol-Prokopczyk, PhD, an associate professor of sociology at the University of Buffalo. “We were excited to identify state characteristics that reduce residents’ risk of pain.”

Grol-Prokopczyk and her colleagues looked at data for over 400,000 adults who participated in the 2017 Behavioral Risk Factor Surveillance System, along with data from all 50 states on social assistance and anti-poverty programs such as the Earned Income Tax Credit, Medicaid and Supplemental Nutrition Assistance Program (SNAP), more commonly known as food stamps.

Their findings, published in the journal PAIN,  show the risk of joint pain was significantly higher in states in Appalachia, the Mississippi Valley and the South, compared to states in the Upper Midwest and West.

Nearly one in four adults in West Virginia (23.1%), Alabama (21.6%) and Arkansas (21.4%) had moderate to severe joint pain. States with the lowest risk of joint pain are Minnesota (6.9%), Hawaii (7.5%) and Utah (7.7%).

SOURCE: PAIN

Digging deeper into the data, researchers found that educational disparities are also associated with pain frequency. People who did not complete high school in West Virginia (31.1%), Arkansas (29.7%) and Alabama (28.3%) were far more likely to have joint pain compared to those with bachelor degrees in California (8.8%), Nevada (9.8%) and Utah (10.1%).

People with less education are more likely to have blue-collar jobs requiring manual labor that may contribute to joint pain. They also have lower incomes and less access to healthcare.

“Education can function as a ‘personal firewall’ that protects more highly educated people from undesirable state-level contexts, while increasing the vulnerability of less educated individuals,” said first author Rui Huang, a sociology PhD student in the UB College of Arts and Sciences.

Researchers also found that states with higher levels of SNAP benefits, social support and community health services had lower levels of pain frequency.

“The increase in the generosity of SNAP benefits could potentially alleviate pain by promoting healthier eating habits and alleviating the life stress associated with food insecurity,” says Huang. “Social factors such as conflict, isolation and devaluation are also among the ‘social threats’ that can lead to physical reactions such as inflammation and immune system changes.”

Previous studies at the University of Buffalo have found that gender, poverty and education play a role in pain frequency and that the overall prevalence of pain is increasing in the United States, affecting virtually every age group, sex, ethnicity and demographic.

Every Brain Has Unique ‘Pain Fingerprint’

By Pat Anson, PNN Editor

They say no two fingerprints or snowflakes are alike. The same may also be true about pain perception.

UK researchers say brain waves -- called gamma oscillations – vary so much from person to person they could be called “pain fingerprints.” That may explain why there is such wide variability in how we feel pain and respond to it.

Scientists at the University of Essex subjected 70 people to brief touch and pain stimulation with a laser, while their gamma oscillations were monitored with an electroencephalogram (EEG), a test that measures electrical activity in the brain using small electrodes attached to the scalp.

The study findings, published in the Journal of Neurophysiology, showed that every participant’s gamma waves had distinct patterns when stimulated, with major differences in the timing, frequency and location of the gamma oscillations. Some had no gamma response when subjected to pain, while others had a large response. 

“Not only, for the first time, can we pinpoint the extreme variability in the gamma response across individuals, but we also show that the individual response pattern is stable across time,” said lead author Elia Valentini, PhD, a Senior Lecturer in the Department of Psychology and Centre for Brain Science, University of Essex. 

“This pattern of group variability and individual stability may apply to other brain responses, and characterizing it may allow us to identify individual pain fingerprints in the activity of the brain.” 

JOURNAL OF NEUROPHYSIOLOGY

Previous studies of how pain changes gamma waves focused on group data, while overlooking individual differences. As a result, some scan results were discarded as background noise, leading to false conclusions.  

The new study found that every participant’s gamma waves were highly individual and “remarkably stable.” It’s not clear why there is such variation between individuals, but Valentini hopes his study will change the way gamma oscillations are measured in future research. 

“I think we need to go back to square one because past findings on the relationship between pain and gamma oscillations do not represent all the participants,” he said. “Our results indicate that current EEG measures do not reflect the complex reality of the diverse individual response patterns to brief pain and touch experiences.”

New research could lead to a better understanding of how we perceive and manage pain. Instead of one-size-fits-all therapies, future treatments could be tailored to our individual “pain fingerprints.”

Mood Disorders May Be Early Sign of Chronic Fatigue

By Pat Anson, PNN Editor

Anxiety, depression and other mood disorders have long been associated with fibromyalgia, irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS). That’s not altogether surprising, since the three chronic illnesses cause body pain, insomnia, fatigue, and other stressful symptoms that can trigger a psychological reaction. No one likes being sick, after all.  

But a large new study found that psychiatric disorders preceded the development of fibromyalgia, IBS and CFS in about a quarter of the people who have the conditions – more than those who suffer from similar chronic illnesses. Anxiety and depression were significantly more common in people who were later diagnosed with chronic fatigue.

"This work provides evidence that for many people, a wide variety of physical and psychological factors are associated with these debilitating conditions," says Francis Creed, a professor emeritus of psychiatry at The University of Manchester.

Creed analyzed over two years of health data from over 120,000 people who participated in the Dutch Lifelines cohort study; comparing the data of people with fibromyalgia, IBS and CFS to those with diabetes, inflammatory bowel disease (IBD) and rheumatoid arthritis. The latter group had similar symptoms and served as a control.

Creed’s findings, recently published in the journals PLOS ONE and Frontiers in Psychiatry, showed that psychiatric disorders were more common (17–27%) in the first group than in the control group (10.4–11.7%).

General anxiety disorder (GAD), panic disorder, dysthymia, major depressive disorder (MDD) and agoraphobia were particularly more common in people who were later diagnosed with CFS.  

PLOS ONE

Creed says a number of physical and mental health issues may be at work in the development of fibromyalgia, IBS and CFS. He favors a holistic approach to treating them, including a mental health evaluation.   

"When people suffering from CFS/ME, IBS and fibromyalgia come into contact with health professionals, negative attitudes can sometimes get in the way of treatment. but by understanding these complex conditions better, the stigma and mystery around them can be eased," he said.

"Although there are symptomatic treatments which may help these unexplained disorders, we should aim to understand fully their underlying causes. There are probably several different ways they may develop; a whole range of physical and mental factors are probably involved. Treatment approaches will become more effective as our understanding of the causes improves."

Association is not causation, and it’s important to note that about three-quarters of the people who developed fibromyalgia, IBS and CFS did not have any mood disorders prior to the onset of their illnesses.   

Creed says future research and clinical work should focus on possible interactions between psychiatric disorders and other behavioral variables to identify the true role of anxiety and depression in chronic illness.

Regular Exercise Boosts Pain Tolerance

By Pat Anson, PNN Editor

People who remain physically active over a long period have much greater pain tolerance than those who are sedentary and don’t get much exercise, according to a large new study in Norway.

While exercise has long been touted as a way to ease or even prevent chronic pain, this particular study falls short in actually proving it, which we’ll get to later.

Researchers at University Hospital of North Norway analyzed data from 10,732 adults who participated in a large health survey -- the Tromsø Study --- that is conducted periodically in Norway. The researchers used data from two rounds of the study that were conducted seven years apart, one in 2007-2008 and the other in 2015-2016.

Most of the participants (79%) said they were either sedentary or engaged in only light exercise, while the remainder reported moderate or vigorous activity. About a third of the participants (32%) said they had chronic pain,

Pain tolerance was assessed by how long they could keep a hand immersed in cold water that was a few degrees above freezing (3 degrees Celsius or 37.4 degrees Fahrenheit).

The study findings, published in the journal PLOS ONE, showed that participants who reported vigorous physical activity in either round had significantly more pain tolerance than the couch potatoes who maintained a sedentary lifestyle in both rounds.

The good news for couch potatoes is that pain tolerance can be improved. As the chart below demonstrates, people who boosted their physical activity (PA) over time were able to keep their hands in cold water for longer periods, suggesting they have more pain tolerance.

source: plos one

“In summary, these findings suggest that becoming or remaining active at a level above being sedentary, or making a positive change in activity level, over time is associated with higher pain tolerance as opposed to being sedentary or making a negative change,” researchers reported. “Whatever you do, the most important thing is that you do something!”

Interestingly, having chronic pain did not influence the findings one way or another. Researchers found that chronic pain “does not significantly interfere” with the relationship between physical activity and pain tolerance. However, they were hesitant to draw a conclusion from that, saying the findings “might look different” if pain conditions were broken down into different diagnostic groups, instead of under one broad term under the label “chronic pain.”      

Even moderate physical activity is known to stimulate the production of endocannabinoids – cannabis-like substances naturally produced by the body -- which can relieve pain and inflammation. Regular exercise can also help us lose weight, reduce the risk of heart disease, and boost overall health.