Consumer DNA Tests Do Not Accurately Predict Disease

By Dr. Lynn Webster, PNN Columnist

Three years ago, I gave my family members DNA kits as Christmas gifts. I thought the genetic health aspects of the test would be an entertaining exercise -- a bit like visiting a psychic who would read tarot cards to predict the future. I didn’t think of it as a serious medical test, and I made sure my family understood that.

These kits have become very popular. More than 26 million people have taken an at-home genetics test, hoping to learn more about their ancestral background, along with their risks of developing certain diseases. But the tests may not live up to either of those expectations.

The U.S. Government Accountability Office (GAO) sent a report to Congress in 2010 alleging that some DNA testing companies used deceptive marketing and other questionable practices. 

The GAO stated that results from DNA tests were “misleading and of little or no practical use.” Their investigation also uncovered the fact that different DNA testing companies provided different results from the same sample. 

Not only were the test results dubious, but the companies made some deceptive claims. One company alleged the results from their testing could help cure diseases. Another claimed the data could predict at which sports a child would excel.

Admittedly, the accuracy of the tests has improved since 2010, but the tests still are, at best, imperfect.

Our genome (the whole of our hereditary information, encoded in our DNA) contains about three billion genes. Of those, only about 20,000 are responsible for disease. But we are more than our genes. Whether or not we will get most diseases depends on a combination of our genes and environment. This interaction of environment and genes is what we call a phenotype.

Of course, there are genetic mutations that are responsible for specific diseases. Single-gene mutations are responsible for about 10,000 diseases, the majority of which are considered rare. Some of the more common single-gene disorders include sickle cell anemia, cystic fibrosis, phenylketonuria, and Huntington's disease.

However, there is no guarantee that direct-to-consumer DNA kits are capable of detecting all common single genetic mutations. Moreover, the absence of a reported mutation from these kits does not mean the mutation does not exist.

Testing may uncover some benign and interesting traits, though. For example, some genetic kits (but not all) can tell you if you have a gene associated with how your earlobes are shaped, whether your urine has an offensive odor after you eat asparagus, or if you are inclined to dislike cilantro.

The accuracy of the health-related portion of the tests is improving. It is now possible to test for genes that predict a person's risk for certain types of breast and prostate cancers. However, placing too much weight on the results of those tests can be dangerous. For example, the tests do not screen for all types of breast cancer, which can lead consumers to falsely conclude their risk of all breast cancers is low if their test results do not indicate a gene mutation associated with breast cancer.

At best, the types of DNA tests that provide information on single-mutation diseases should be accompanied by appropriate genetic counseling. Since most diseases are based on multiple genes and environment, a genetics counselor can help put the test results into perspective.

Deciding how to use the information may be more important than knowing the results of the test. In medicine, we never order a test unless it will help us provide better care for our patient. This may be an important principle to apply here as well.

Privacy Is a Big Concern

We should also be very concerned about how our DNA data will be stored and used. The testing companies' DNA databases can be hacked by people with nefarious motives, or shared with insurance companies or law enforcement. Laws protecting consumers are evolving, but clearly, at-home DNA tests expose consumers to unknown and, perhaps, unintended consequences.

DNA tests were first pitched to consumers as a way in which they could learn about their ancestry. However, the reference data sets were largely European and less accurate in showing lineages in other areas of the world. If your roots were Asian or African, the reports were less likely to accurately reflect where your ancestors lived.

Over time, the data sets have improved and expanded, so consumers with non-European ancestry may get more accurate information about their heritages now than they would have previously. That trend will likely continue.

Whether DNA kits are mostly a gimmick, I cannot say. But it is important to recognize their limitations in providing trustworthy information about our health or ancestry. Certainly, we should not base health decisions on their results, and I would think twice about paying for the privilege of delivering my DNA profile to a for-profit company.

Maybe this year I’ll just give everyone tarot decks.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is the author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences or Pain News Network. 

U.S. Life Expectancy Still Declining

By Pat Anson, PNN Editor

After decades of progress with Americans living longer and healthier lives, a disturbing new study has documented how life expectancy in the U.S. has declined for three consecutive years.

The drop in life expectancy was most pronounced in young and middle-aged adults. Starting in 2014, midlife mortality increased across all racial groups, largely due to drug overdoses, alcohol abuse, suicide, and chronic illnesses such as hypertension and diabetes. Researchers said prescription opioids were more of a symptom than a cause of premature deaths.

In 2014, Americans were expected to live to 78.9 years of age. By 2017, the average life expectancy had fallen to 78.6 years.

The U.S. now has the worst midlife mortality rate among 17 high income countries, even though it spends more on healthcare per capita than any other nation.  

“This is an emergent crisis. And it is a uniquely American problem since it is not seen in other countries. Something about life in America is responsible,” lead author Steven Woolf, MD, reported in a Special Communication published in JAMA.

The largest increases in midlife mortality occurred among adults with less education and those living in rural areas.  Changes in life expectancy were greatest in upper New England, the Ohio Valley, and Appalachia – regions where economic distress, lower social mobility and the so-called epidemic of despair contributed to rising rates of suicide and drug and alcohol abuse.

“While it’s a little difficult to place the blame on despair directly, the living conditions causing despair are leading to other problems,” said Woolf, who is director emeritus of the Center on Society and Health at Virginia Commonwealth University. “For example if you live in an economically distressed community where income is flat and it’s hard to find jobs, that can lead to chronic stress, which is harmful to health.”

While life expectancy increased in a handful of Western states, midlife mortality rose in Ohio and West Virginia – states often called ground-zero of the opioid crisis.  A sharp increase in opioid overdoses came in three waves; starting with the introduction of OxyContin and the overuse of prescription opioids in the 1990s, followed by increased heroin use, and then the emergence of illicit fentanyl – which triggered another wave of opioid overdoses starting in 2013.

“However, the increase in opioid-related deaths is only part of a more complicated phenomenon and does not fully explain the increase in midlife mortality rates from other causes, such as alcoholic liver disease or suicides. Opioid-related deaths also cannot fully explain the U.S. health disadvantage, which began earlier (in the 1980s) and involved multiple diseases and nondrug injuries,” Woolf said.

The tsunami of fentanyl overdoses has yet to dissipate. According to a new study by the Massachusetts Department of Public Health, 93% of opioid related overdoses in the state in the first nine months of 2019 involved fentanyl. Deaths involving prescription opioids such as oxycodone and hydrocodone peaked in 2014 and are now linked to only about 10% of overdose deaths in Massachusetts.

Criminalizing Pregnant Women for Drug Abuse Is a Terrible Idea

By Dr. Lynn Webster, PNN Columnist

According to Guttmacher Institute, nearly half the states in the United States are willing to punish pregnant women in order to spare their babies the agony of being born with Neonatal Abstinence Syndrome (NAS). Ironically, their efforts are having the opposite effect.

Twenty-three states and the District of Columbia have passed legislation that criminalizes substance abuse during pregnancy. Additionally, 25 states and the District of Columbia require healthcare providers to report expectant mothers who may be illegally using substances. In 8 states, pregnant women who are suspected of substance abuse must also undergo drug testing.

The huge number of babies born to mothers dependent on opioids has driven policymakers to find ways to deter pregnant women from abusing opioids.

But new research points out there are unintended consequences to criminalization. And it provides lawmakers insight on how to create more effective policies that result in positive, not punitive, outcomes.

A study published recently in the journal JAMA Network Open examined 4.6 million births in the U.S. from 2000 to 2014. During this time, the diagnosis of NAS increased seven fold.

The study was conducted by the RAND Corporation, a nonprofit research institute that analyzed 8 states with punitive policies for drug-abusing pregnant women. The research was funded by the National Institute of Drug Abuse.

According to a RAND press release, Arkansas, Arizona, Colorado, Kentucky, Massachusetts, Maryland, Nevada and Utah adopted either punitive penalties for drug use during pregnancy or policies that required health care providers to report pregnant women with suspected illegal substance use.

RAND researchers found that the annual rate of NAS increased in the 8 states, from 46 cases per 10,000 live births to 60 cases per 10,000 after punitive policies were enacted. That is an alarming 30% increase in NAS cases.

This is not the first study that has shown political efforts to curb opioid addiction and overdoses have not had a positive impact. We have seen the harm associated with forced tapers and dose limits adversely affecting millions of pain patients.

It is hard to understand why these destructive policies are put in place, but it may be because policymakers are misinformed or biased. Regardless, it reflects a systemic flaw for governments to fail to evaluate the efficacy and outcomes of the very policies they create.

Addiction Is a Disease, Not a Crime

How best to address addiction has long been the subject of debate. For example, a state hospital in South Carolina illegally obtained the diagnostic tests of pregnant women in an effort “to obtain evidence of a patient's criminal conduct for law enforcement purposes” (this was the case of Ferguson v. Charleston).

Unfortunately, some people still believe that addiction is a volitional or character flaw that should be recognized as criminal behavior rather than a disease.

Indisputably, addiction is a complicated, life-threatening disease. Treating people with the disease as criminals is the worst possible approach. Most experts in the substance abuse treatment community have known this for years. Fortunately, the RAND Corporation has now provided evidence of how this applies to babies born to women who abuse opioids. 

Typically, lawmakers do not evaluate the impact of the policies they pass. There have been many policies over the past few years that were implemented by state legislatures, healthcare organizations and insurance companies that were intended to reduce harm from opioids. Almost no one has attempted to measure their effectiveness or unintended consequences.

Fortunately, in this case, we have an exception. We have a unique opportunity as a result. The RAND study should provide policymakers with insights on how to more effectively address the problem of substance abuse during pregnancy.

Threatening to punish a pregnant women does not decrease the number of women who abuse drugs. However, it does scare many of them away from seeking the treatment they need and can deter pregnant mothers from seeking prenatal care.

Pregnant women who are opioid-dependent frequently use other illegal substances that risk the health of their babies. There should not be more barriers for pregnant women to receive prenatal care. Infants born after exposure to opioids often require prolonged hospitalizations to manage their needs, with those cumulative costs totaling more than $500 million, according to the RAND study. More importantly, babies with NAS suffer needlessly.

It should go without saying that every policymaker wants to solve problems and not create additional harm for new mothers or to babies born to them. Hopefully, this study will be used as it is intended: to help create policies that actually reduce harm from opioids. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is the author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences or Pain News Network. 

FDA Approval Gives New Hope to Patients With Rare Genetic Disease

By Pat Anson, PNN Editor

Lisa Kehrberg was once frightened about her future. For years the retired family practice doctor and mother of two would suffer severe bouts of unexplained abdominal pain, headaches and nausea that would leave her hospitalized for weeks at a time.

“I was doubled over, rocking, vomiting and crying with the worst pain of my life. Worse than labor, appendicitis, or anything else I'd experienced. It was a hot, burning pressure that was like lava and hot razor blades filling up my abdomen,” Lisa recalled.

She was eventually diagnosed with a rare genetic disease called acute intermittent porphyria, which causes toxic molecules to build up in the body. The same disease killed Lisa’s brother in 2011. And she thought the same fate awaited her.

“One of the most common causes of death from porphyria is suicide. This isn't surprising. I always wonder how people who are sick like me keep surviving. To live in continuous excruciating pain every minute of every day with no end in sight is quite the challenge,” Lisa wrote in a 2016 column for PNN.

It was about that time that Lisa entered a clinical trial program. Every four weeks she’d travel to Houston from her home near Chicago for injections of an experimental drug. Over time, her symptoms began to improve and the porphyria attacks that used to occur monthly became less frequent.

LISA KEHRBERG, MD

Like other participants in clinical studies, Lisa wasn’t allowed to talk publicly about the drug she was getting – until now.  

The Food and Drug Administration has just approved the use of Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria (AHP). Approval was granted based on results from placebo controlled trials involving 94 porphyria patients. Those who received Givlaari experienced 70% fewer porphyria attacks compared to patients receiving a placebo.  

“Prior to getting givosiran I was bed-bound for close to 6 months straight from severe muscle weakness and paralysis issues. I no longer have paralysis and most of the muscle weakness has resolved,” Lisa said in an email. “The rate of new attacks has decreased greatly, finally giving my nerves a chance to heal after 22 years of attacks and 6 years of back-to-back attacks.”

“These attacks occur suddenly and can produce permanent neurological damage and death,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement Wednesday. “Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”

The FDA approved Givlaari under its breakthrough therapy, priority review and orphan drug designations, which provide incentives to companies in the development of drugs for rare diseases. Approval was granted to Alnylam Pharmaceuticals, which expects Givlaari to be available to healthcare providers by the end of the year.

There are about 3,000 people diagnosed with active porphyria in the U.S. and Europe. Due the wide array of symptoms the disease has, it can take years before an accurate diagnosis is made.

“The FDA approval of Givlaari is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director of the American Porphyria Foundation.

Image courtesy of Alnylam Pharmaceuticals

“AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of Givlaari is exciting for our community.”

Lisa Kehrberg isn’t out of the woods just yet. She has permanent nerve damage from years of porphyria attacks. But her future is a lot brighter than it was.  

“For newly diagnosed patients, I strongly believe this treatment has the ability to stop the progression of the disease and will allow patients to lead a normal, functional life,” she says. 

EPA Decision Will Stifle Animal Research on New Pain Treatments

By Dr. Lynn Webster, PNN Columnist

People in pain rely on scientific advances to find safer, more effective alternatives to opioids. Animal research is key to many of our advances in drug development.

But a recent announcement from the Environmental Protection Agency threatens to change that -- by inhibiting science’s ability to replace opioids and create new life-saving pain interventions.

EPA administrator Andrew Wheeler announced in September the agency's decision to "significantly curtail its reliance on the use of mammals in toxicological studies conducted to determine whether environmental contaminants have an adverse impact on human health."

The EPA plans to reduce funding for most mammal studies by 30% by 2025 and eliminate them altogether by 2035.

The agency also announced that five universities would receive $4.25 million in federal funding to develop alternatives to reduce or replace the use of animals in research.

Ostensibly, Wheeler worries about the potential mistreatment of animals used in testing. But Natural Resources Defense Council (NRDC) scientist Jennifer Sass believes he may be politically motivated.

“The Trump administration appears to be working on behalf of the chemical industry and not the public,” Sass said in an NPR interview.

Most likely, the American Chemistry Council, which represents chemical companies, would prefer to eliminate mammal studies that could prove the toxicity of their products. Wheeler, however, claims he hasn't talked to "a single chemical company about this."

According to The New York Times, the American Lung Association, the American Heart Association, and the American Medical Association disagree with Wheeler's strategy. Lab-grown cells and computer modeling can reduce the need for animal testing. But Penelope Fenner-Crisp, a former senior official at the EPA, believes 2035 may be too soon to ban all animal studies.  

"There's currently no substitute for [testing] some of the more complex and sophisticated toxicities, such as the effect of chemicals on animals' reproductive systems," she said.

The NRDC, an environmental advocacy group, also opposes the EPA's plan to ban animal testing on the grounds that it could make it harder to identify toxic chemicals and protect human health.

Animal research has played a key role in developing many new technologies, including MRIs, ultrasounds, CT scans, and new surgical techniques. It has also played an integral role in the development of vaccines, pain relievers and other medications, as well as life-saving emergency care.

“Virtually everything a doctor, nurse, veterinarian, veterinary technician, paramedic, or pharmacist can give the injured or sick was made possible by animal research," says Dr. Henry Friedman, a neuro-oncologist who leads the opposition to the EPA decision.

Dr. Friedman says sophisticated computers can be helpful in many areas of scientific research, but they "can't predict everything a new drug will do once inside you." He also maintains that laboratory animals are treated humanely under strict guidelines.

Speaking of Research, an international advocacy group that supports the use of animal research, believes the EPA's plan endangers human, animal and environmental health.

"This directive flies in the face of the EPA’s mission to 'protect human health and the environment' and 'to ensure that national efforts to reduce environmental risks are based on the best available scientific information.' Animal-based research and testing is critical for understanding how new chemicals and environmental substances affect human and non-human animals," the organization said in a statement.

Many of us in the scientific community oppose the EPA’s decision because it could slow drug development and threaten our ability to find safer and more effective treatments for pain, addiction and other diseases. If the EPA decision is sustained, it will be a major obstacle to the advancement of medical science.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is the author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences or Pain News Network.

Chronic Pain Often Leads to Frailty in Older Mexican Americans

By Pat Anson, PNN Editor

A new study has found that leaving chronic pain untreated or poorly treated can have serious health consequences for senior citizens. Older Mexican Americans who suffer from pain are 1.7 times more likely to become frail, according to findings published in the Journal of Pain.

Frailty is characterized by unintentional weight loss, weakness, exhaustion or slowness in older adults. Chronic pain is a risk factor for frailty in all older adults, but not enough is known about the relationship between pain and frailty in older Latino populations, the fastest growing segment of older adults in the United States.

To learn more about it, researchers at the University of Texas Medical Branch, Galveston, followed over 3,000 Mexican Americans aged 65 or older. Data was collected from 1995 to 2013.

At the start of the study, participants were asked if they experienced pain in the previous month. Social, health and demographic data were also collected, such as age, sex, marital status, literacy, mental health, disability and medical conditions. Those categorized as frail were not included in the study.

Eighteen years later, 41 percent of the participants who reported pain were considered frail. Old age, hip fractures, depression and disability were also associated with higher odds of becoming frail.

Researchers say older Mexican Americans are particularly prone to frailty because they often have poor access to medical care. They are also nearly twice as likely as non-Hispanic whites to suffer from type 2 diabetes, a leading cause of peripheral neuropathy.

“Older Mexican Americans are an underserved population with disparities in healthcare access and delivery and health risks associated to their demographic group,” said Eliseo Pérez-Stable, MD, Director of the National Institute on Minority Health and Health Disparities. “This study identifies the need to effectively manage pain in Latino populations by culturally appropriate interventions.”

Women in the study who had higher levels of education or higher mental agility scores were found to have less risk of becoming frail.

“The relationship between social determinants, diabetes, physical function, mobility, frailty and pain in older Mexican Americans is complex and poorly understood,” said Kenneth Ottenbacher, PhD, the study’s principal investigator. “Early assessment and better pain management may prevent early onset of frailty in this group.”

The study was funded by the National Institutes of Health.

Young Women Abused as Children Have More Pain

By Pat Anson, PNN Editor

Young adult women with a history of being physically or emotionally abused as children report higher levels of pain than women not abused in childhood, according to a new study.

The link between child abuse and chronic pain in adulthood is a controversial one, but there are a number of studies that have found an association between the two. This was one of the first to follow abused adolescents into adulthood.

Researchers at Cincinnati Children's Hospital Medical Center recruited 477 girls between the ages of 14 and 17 and followed them up to age 19. About half the girls experienced neglect or maltreatment, such as physical, emotional or sexual abuse that was substantiated by child welfare records. The other half acted as a control group.

Five years later, researchers contacted the women again and surveyed them about their pain as young adults. Those who were maltreated as children reported higher pain intensity, a greater number of pain locations, and were more likely to have experienced pain in the previous week than those who were not mistreated as children.

The young women who experienced post-traumatic stress as teenagers had the highest risk of pain.

"Child maltreatment and post-traumatic stress symptoms (PTSS) in adolescence work together to increase risk of pain in young adulthood," says lead author Sarah Beal, PhD, a developmental psychologist at Cincinnati Children's Hospital Medical Center. "The link isn't simple and could be due to an increase in inflammation, maintaining a state of high-alert in activating stress responses, or a number of other psychological or behavioral mechanisms.

“Women with a child maltreatment history were significantly more likely to experience pain and report a higher number of pain locations in young adulthood. Furthermore, among women who experienced any pain, those who were maltreated reported somewhat higher pain intensity. Results also showed that elevated PTSS during adolescence were associated with pain in adulthood and more widespread pain.”

Beal, who reported her findings in the journal Pain, says identifying and treating childhood trauma at an early age could help prevent chronic pain from developing in adulthood.  

“By intervening to address stress symptoms and poor coping following maltreatment, we may be able to reduce the impact of maltreatment on young adult health sequelae -- at least for pain,” said Beal.

Previous research has found an association between childhood trauma and chronic illness in adults.

A recent study found that women who experienced physical or emotional abuse as children have a significantly higher risk of developing lupus, a chronic autoimmune disease.

Another study found that adults who experienced adversity or trauma as children were more likely to have mood or sleep problems as adults -- which in turn made them more likely to have physical pain.

And a large survey found that nearly two-thirds of adults who suffer from migraines experienced emotional abuse as children.

Can We Forget About Chronic Pain?

By Ann Marie Gaudon, PNN Columnist

I recently came across a clinical report which describe two patients with a lengthy history of chronic pain severe enough to warrant opiate therapy. Both patients experienced sudden memory loss and forgot about their pain – literally.

Central sensitization is a process known to occur in the spinal cord and brain where if short-term acute pain is allowed to persist, then changes occur within the central nervous system which can lead to chronic or intractable pain.

That’s what happened to me. I have a diagnosis of a visceral pain syndrome, as opposed to a progressive pain condition. I experienced one vicious organ assault and after more than 30 years of it being healed, I remain in pain.

Other patients who have experienced painful trauma may relive painful episodes that evoke recurring memories -- they experience their pain over and over again. That is a classic symptom of post-traumatic stress disorder (PTSD). Think of a war veteran or survivor of sexual violence.

Either way, neurophysiologic changes which relate to learning, memory and pain can result in a maladaptive learning process which leaves one in chronic pain. These intricacies happen outside of conscious awareness. We are not aware of or in control of this dysfunctional process while it is occurring within our brain and spinal cord circuits.

Here is an overview of the two patients discussed in the report:

Patient #1

The first patient is a 47-year old female with complicated health problems. She had undergone multiple surgeries and treatment modalities for gastric ulcers, endometriosis, thyroid cancer, hypothyroidism, seizure disorder, malnutrition and chronic abdominal pain over 10 years.

Her pain was managed with high doses of opiate medications in various forms, including intravenous, transdermal and oral. During a complex 12-month hospital stay, she had at least five seizures and suffered memory loss so severe she could not remember her entire stay in the hospital.

She did eventually become fully alert and oriented to the present, but she no longer complained of her pain symptoms and no longer demonstrated a need for consistent pain medication.

Six months after discharge, the patient was living at home in stable condition and only occasionally using tramadol. She reported her symptoms as minimal and 1-2 on the pain scale. She still has no memory of many aspects of her long hospitalization.

Patient #2

A 57-year old male was described as a “highly functioning architect” with a 10-year history of low back and right extremity pain. He had undergone many unsuccessful treatments for pain, including surgery, and was being admitted to hospital to have an intrathecal pump surgically implanted for pain control. He was taking no less than nine medications for pain including high doses of opiate therapy.

Initially after the pump was placed, he reported having a partial reduction of pain in his leg. However, in the next six months he was requesting higher doses of intrathecal as well as oral opiates.

One month after this, the patient was in a minor motor vehicle accident where he did not lose consciousness, but inexplicably had partial memory loss. His physicians felt the accident was not the cause, as the memory loss symptoms occurred long afterward. The cause of the amnesia was unknown and tests including a brain MRI showed as normal.

The patient could not remember the names of his doctors, where he lived, what type of work he did, or why he had a pain pump implanted. He was weaned off opiates without any complaint of increased pain and subsequently had the pump removed at his request.

Eight months later, this patient was found minimally responsive in his home. It is not known what occurred, but there was a suspicion that he had fallen and incurred a head injury. The patient experienced profound memory loss, with no memory of who he was, his family members or his back pain.

His pain medications were discontinued with no complaint of pain, but he required placement in a long-term care home due to severe amnesia. Over the next two years, this patient regained partial memory, along with some back and leg pain. He has not requested or required opiate therapy.

Emotions, Pain and Memory

We know pain perception can be caused by nociceptive stimuli, yet we also know that emotional and psychological factors can increase our perception of pain. A complex play of nerve fibers which transmit messages to the brain and spinal cord suggest there is a relationship between emotions, pain and memory. The best evidence that memory plays a role in pain is that of phantom limb pain.

The two cases presented here suggest that memory may influence the perception of pain, and that amnesia can be accompanied by a loss of or significant reduction of pain in the absence of any physical factors.

Treatments that reduce “pain memories” in the brain and spinal cord, along with a focus on preventing pain to reduce or eliminate these memories, may someday have a more widespread role in the management of chronic pain. To have a treatment or ability to effectively erase a maladaptive pain memory leaves me with just three words:

Count me in.

Ann Marie Gaudon is a registered social worker and psychotherapist in the Waterloo region of Ontario, Canada with a specialty in chronic pain management. 

Ann Marie has been a chronic pain patient for over 30 years and works part-time as her health allows. For more information about her counseling services, visit her website.

This column 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.

Seeing Red: How Colors Affect Pain

By Dr. Lynn Webster, PNN Columnist

It is a myth that the matador’s red cape -- the muleta -- incites rage in the bull and causes him to charge. The truth is, all cattle are colorblind.  The bull does not charge because of the color, but because of the movements of the matador and his cape.

It is not a myth, however, that color can affect the moods of humans. Researchers have studied how colors affect psychological states, such as anxiety, in people.

We now know that color also affects how people perceive pain. In this month’s issue of Pain Medicine, authors Karolina Wiercioch-Kuzianik and Przemyslaw Babel present “Color Hurts: The Effect of Color on Pain Perception,” exploring how color can affect the perception of pain.

A 2007 study reported more intense pain when a painful stimulation was preceded by a red color than a blue one. The new study builds on that work through two experiments.

In the first, 30 volunteers were shown six colors, one at a time, followed by mild electric shocks to their forearms – seven shocks with each color.

The participants, who knew in advance what the research would involve, reported their pain on a scale of 0 to 10 following each stimulation.

A black image was the control to which all the colors were compared. Black was chosen as the control because it is regarded as the absence of color.

The investigators found that the color red produced the most intense pain, followed by green and blue. Other colors were associated with less pain.

The results are not necessarily intuitive. Red may bring people joy when it takes the form of blooming roses, succulent berries, or wonderful memories of Christmas. But in this study, red increased pain levels.

The second experiment was designed to assess whether colors would affect the expectation of pain and pain intensity. Participants viewed a color and then received a series of mild electric shocks. Again, pain intensity was rated higher with some colors, particularly with red, blue and green. The investigators did not observe that specific colors influenced the participants' expectation of pain intensity.

Much has been written about how and why colors can affect our cognition and behavior. Our reactions to colors seem to be a result of biology and cultural imprinting. Interestingly, many people are aware that individuals supposedly have a “personality color.” Human resource professionals have even used color personality tests to assess job applicants.

Our folklore and traditions bestow certain meanings to colors. Snow White represents purity and innocence, while Edgar Allen Poe used a black raven to symbolize death. The Great Gatsby and other stories use the color gold to suggest greed.

Colors affect us psychologically and physically. As the authors of the Pain Medicine study concluded, colors can also influence our perception of pain. Thus, it may be important for researchers and clinicians to recognize that a patient's reported pain could be affected by the colors of the exam room or even the ambiance of a clinic.

It may be time to for people in pain to consider how their choices of clothes, furnishings, and even paint and wallpaper may factor into their levels of comfort.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences.

Discovery of Brain Protein Could Lead to New Chronic Pain Treatments

By Pat Anson, PNN Editor

Researchers have identified a protein in the brain that appears to play a prominent role in the maintenance of long-term pain -- a discovery that could lead to new treatments that stop short-term acute pain from progressing to chronic pain.

The protein RGS4 (Regulator of G protein signaling 4) is found in brain circuits that process pathological pain, mood and motivation.

"Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain," says Venetia Zachariou, PhD, a professor in The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai in New York City.

"Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it's exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain."

In studies on genetically modified mice, Zachariou and her colleagues found that genetic inactivation of RGS4 did not affect acute pain, but it promoted recovery from nerve injuries, chemotherapy-induced neuropathy and peripheral inflammation. Mice lacking RGS4 developed all the expected symptoms of a nerve injury, but recovered within 3 weeks and returned to physical activity.

The transition from acute to chronic pain is accompanied by numerous adaptations in immune, glial and neuronal cells, many of which are still not well understood. Chronic pain patients experience a number of debilitating symptoms besides pain, such as sensory deficits, depression and loss of motivation

Researchers believe future drugs that target RGS4 could prevent acute pain from transitioning to chronic pain. Currently available medications for chronic pain only treat the symptoms – not the underlying condition – and have major side effects.

Dr. Zachariou's laboratory is conducting further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which the protein affects sensory and pain symptoms.

Their findings are published online in The Journal of Neuroscience.

The Complex Relationship Between Alcohol and Pain

(Editor’s note: A recent PNN survey found that nearly 20% of chronic pain patients used alcohol for pain relief. Many do so because they lost access to opioid medication. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recently published this article on pain and alcohol, and invited PNN to republish it.)

The relationship between alcohol and pain is a complicated one. It is a common belief that alcohol dulls pain, yet research shows that sometimes alcohol can make pain worse.

Understanding the complex relationship between alcohol and pain is an important area of research for NIAAA. In 2016, about 20 percent of adults (50 million people) in the United States had chronic pain, defined as pain most days in the previous 6 months. Recent studies suggest that around 1 in 4 adults in chronic pain reports self-medicating with alcohol, and 43–73 percent of people with alcohol use disorder (AUD) report experiencing chronic pain.

An improved understanding of the effects of alcohol on pain, the role of pain in alcohol misuse, and potential interactions between alcohol and opioids during pain treatment hopefully will improve treatment outcomes for patients in pain.

Alcohol has been found to alleviate physical pain, but it requires doses consistent with binge drinking to do so. Binge drinking is defined as drinking enough to bring blood alcohol concentration (BAC) levels to 0.08 percent, which typically occurs after 4 drinks for women and 5 drinks for men in about 2 hours.

A recent analysis of the findings from 18 studies on alcohol and pain concluded that a BAC of 0.08 percent produces a small increase in pain threshold and a reduction in pain intensity. These findings could help explain why some people with chronic pain drink excessively.

Unfortunately, reaching BAC levels this high also is associated with unintentional injuries, violence, traffic fatalities, and other consequences. And long-term excessive drinking makes physical pain worse. In a group of 30 men in treatment for AUD, sensitivity to pain increased early in abstinence.

People also sometimes use alcohol in an effort to cope with emotional pain. Unfortunately, as with physical pain, the temporary reprieve alcohol might offer gives way to an increase in emotional pain when the alcohol wears off.

Chronic alcohol misuse can lead to the emergence of a negative emotional state, known as hyperkatifeia, in between episodes of drinking. The resulting irritability, dysphoria, and anxiety fuel further alcohol use. As with physical pain, drinking alcohol to cope with emotional pain makes the situation worse. (For more information, see “Alcohol and ‘Deaths of Despair.’”)

Opioid analgesics commonly are prescribed to treat physical pain and often are misused to cope with emotional pain. Used separately, alcohol and opioids can cause overdose deaths by suppressing areas in the brain stem that control breathing. Using alcohol and opioids together amplifies the danger. Research suggests that alcohol plays a role in around 1 in 5 deaths from opioid overdoses.

Because the mechanisms by which alcohol and opioids reduce physical and emotional pain overlap, regular use of one drug diminishes the effects of the other. For instance, when researchers examined opioid pain medication use after abdominal surgery in more than 4,000 patients, they found that frequent alcohol consumption was associated with increased opioid use for pain control.

Similarly, in rats allowed to drink alcohol for 8 weeks, opioids became less effective at reducing physical pain. Withdrawal from opioids, like withdrawal from alcohol, leads to the emotional misery of hyperkatifeia.

As part of the National Institutes of Health Helping to End Addiction Long-Term (HEAL) initiative, NIAAA is encouraging studies to develop and validate biomarkers of comorbid alcohol misuse and chronic pain and that address alcohol misuse in the context of chronic pain management.

NIAAA also encourages research on the impact of alcohol and sleep disturbances on pain through a new funding opportunity. These efforts, among others, should shed light on how alcohol affects pain and vice versa and could have implications for both treating AUD and managing chronic pain.

Opioid Breathalyzer Test Developed

By Pat Anson, PNN Editor

Chronic pain patients have grown accustomed to having their urine -- and sometimes their blood and hair – analyzed for opioids and other drugs.

Someday soon they could be taking opioid breathalyzer tests.

In a small pilot study, researchers at the University of California, Davis have developed and successfully tested a device that collects minute droplets in breath that can be analyzed in a laboratory for morphine, hydromorphone (Dilaudid) and other opioids.

“Exhaled breath collection represents a painless, easily available, and non-invasive technique that would enable clinicians to make quick and well-informed decisions,” said lead author Cristina Davis, PhD, chair of the Department of Mechanical and Aerospace Engineering at UC Davis. "There are a few ways we think this could impact society."

While ostensibly developed to help doctors care for patients and monitor their drug use, Davis and her colleagues say opioid breathalyzer tests could someday be used in addiction treatment and by law enforcement during roadside field sobriety tests.

They reported their findings in the Journal of Breath Research.

IMAGE COURTESY OF CRISTINA DAVIS, UC DAVIS

“Breath offers the opportunity to collect a diagnostic biospecimen non-invasively and, eventually, a way to obtain near real-time results almost anywhere. Though this study did not utilize portable analytic systems, future breath drug detection platforms used to identify targeted compounds will be available for point-of-care use. This will enable opioid detection in many settings including roadside, drug treatment facilities, field emergency response, home, and rural areas with limited access to healthcare,” Davis wrote.

Nine patients receiving opioids for cancer pain at the UC Davis Medical Center participated in the pilot study, along with three healthy people used as a control group. Participants exhaled through a glass tube surrounded by dry ice that captured and froze breath condensate. The breath samples was then analyzed in a lab using mass spectrometry and compared to opioid metabolites in blood samples and in doses given to patients.

"We can see both the original drug and metabolites in exhaled breath," Davis said.

Fully validating the breath test will require more data from larger groups of patients. UC Davis researchers are working towards the development of real-time, point-of-care breath tests that can be broadly used to detect opioids and other drugs.

Point-of-care (POC) urine drug tests are widely used by doctors to screen patients for illicit drugs and to make sure they’re taking medications as prescribed. Physicians like the immunoassay test strips because they can be performed in their offices, are inexpensive and give immediate results.

However, as PNN has reported, POC test results are wrong about half the time – and frequently give false positive or false negative results for drugs like marijuana, oxycodone and methadone.  Experts say doctors should never base a treatment decision or discharge a patient solely on the results of one POC test, and that confirmatory testing should always be performed by a laboratory. 

Can Prayer Ease Chronic Pain?

By Dr. Lynn Webster, PNN Columnist

Does prayer lead to healing? Many religious people around the world believe that it does. According to the science, it may.

Medical researchers have looked into the effects of religion and spirituality on chronic health conditions, including chronic pain, for many years. The research has produced vastly different results. According to a review of studies in the Indian Journal of Psychiatry, prayer may contribute to healing, may worsen health, or may make no difference at all.

Helen Fosam, PhD, says in Clinical Pain Advisor, "a positive emotional state and a positive expectation of pain relief can lower pain and enhance clinical effect of treatment."

So if you believe prayer can ease your pain, it may happen.

Pain Is a Spiritual Condition

As I say in my book, The Painful Truth, pain is a bio-psycho-social-spiritual condition. However, it might make more sense to reverse the order and put “spiritual” first because, for many people, the spiritual dimension is the most important.

More times than I can remember, I’ve known people in pain to cry out to God for mercy, kneel in silent prayer, cross themselves or finger their rosary, practice yoga or meditation, wear crosses or angel pins or crystals, express a longing for heaven, mention attending religious services, or tell me about their belief in God.

Even religious skeptics who are in pain sometimes pray for themselves or ask others to pray for them.

The simple fact is that most people have a tendency to turn to God and faith when they are in need, including when they are in pain. Along with most other pain specialists, I have come to see this as generally a good thing, because relating to a God or a perceived spiritual reality beyond oneself can affect one’s pain experience positively.

Prayer As Meditation

Prayer is a specialized form of meditation. According to the National Center for Complementary and Integrative Health, meditation "may be helpful for a variety of conditions, such as high blood pressure, certain psychological disorders, and pain."

People who have faith in a higher power and turn to prayer may be availing themselves of the medical benefits of meditation.

Of course, not everyone who is in pain is religious or spiritual -- or wants to be. I’ve known many people with pain who have experienced a substantial increase in their life satisfaction without recourse to spiritual beliefs and practices. Some of them have practiced meditation, and some of them have not.

But if we’re interested in what promotes healing for those enduring long-term pain, we can’t ignore the interaction between belief and pain.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD. 

Chronic Pain Accelerates Dementia

By Dr. Lynn Webster, PNN Columnist

In 2017, JAMA Internal Medicine published a study that found older people with chronic pain experience faster declines in memory and are more likely to develop dementia.  While prior research had shown a link between chronic pain and brain damage, this was one of the first studies to specifically suggest that chronic pain can cause dementia.

The authors reported that people aged 60 and over with persistent pain experienced a 9.2% more rapid decline in memory score when compared to people of the same age without chronic pain. This means that people with chronic pain may experience more difficulty in managing their finances, medications and social connections.

Dementia is a chronic condition of the brain that involves memory, personality and judgment. It is not a disease; it is a symptom of one or more diseases.

There are many types of dementia. Alzheimer’s disease is considered to be the most common.

Dementia usually worsens over time if the underlying disease remains static or progresses, as is the case with many chronic pain conditions.

There are an estimated 20 million Americans with high impact (the most severe) chronic pain who may be experiencing accelerated decline in cognition due to their pain. The amount of dementia appears to be associated with the severity and duration of chronic pain. Undertreated or untreated chronic pain may accelerate dementia.

Chronic pain affects an even larger percentage of elderly adults (one in three) than the general population. Since the prevalence of chronic pain increases with age, the probability of experiencing dementia increases as well. However, the reasons for that go beyond aging itself.

Seniors are more likely to take multiple medications that can contribute to mental confusion. On average, elderly people take five or more prescriptions. They may also use over-the-counter medications, which adds to potential drug-associated mental compromise.

Opioids, in particular, have been implicated in cognitive impairment. However, a study published in 2016 suggests there is no difference in cognitive decline between people on opioids and those on nonsteroidal anti-inflammatory drugs. The study's implication is that pain, not opioids, leads to cognitive impairment.

Brain Fog

Chronic pain appears to affect the function and structure of the hippocampus. This is the region of the brain that involves learning, memory, and emotional processing.

One explanation for the mental decline associated with chronic pain is that various areas of the brain compete for attention. Attentional impairment compromises memory by diverting attention to the areas of the brain processing pain. In effect, the brain is multi-tasking and favoring the processing of pain over cognition. This may, in part, explain the clinical phrase “brain fog.”

The Australian Broadcasting Company's "All in the Mind" website explains that pain damages the brain in several ways, including a change in the size of the thalamus and a decrease in the amount of a neurotransmitter (gamma-aminobutyric acid) the brain produces. In other words, chronic pain changes the brain structurally and functionally.

The prefrontal cortex is the part of the brain responsible for executive functions, such as cognition, social behavior, personality, and decision-making. It is also the part of the brain that modulates pain.

According to "All in the Mind," some researchers believe that chronic pain decreases the volume of the prefrontal cortex. Over time, brains damaged by pain lose the ability to handle pain — along with some of the personality attributes that make us who we are.

Brain Damage Can Be Reversed

The good news is that the brain damage caused by chronic pain can be reversed, at least to some extent. Unfortunately, the elderly are less likely to recover from dementia caused by chronic pain as compared with younger patients.

If pain is adequately treated, the brain may be able to regain its ability to function normally. A 2009 study of patients with chronic pain due to hip osteoarthritis showed reversal of brain changes when their pain was adequately treated. 

People who don’t have their acute pain managed are more likely to develop chronic pain. It is postulated that the changes in the brain that occur with chronic pain begin with the onset of acute pain. There is also some evidence that an individual’s genes may influence who is at greatest risk for developing brain damage from chronic pain and who is least likely to recover from it. 

Many people have criticized the concept of assessing pain as the 5th vital sign, and have called it a contributing factor for the opioid crisis. As I have said, pain may not be a vital sign, but it is vital that we assess it. Asking patients about their pain is critical to providing interventions that can mitigate the consequences of undertreated pain, including dementia. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD. 

The information in this column 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.

Fibromyalgia Researchers, It’s Time to Stop Watching the Flowers Grow!

By Donna Gregory Burch

As a fibromyalgia warrior and blogger, I read a lot of articles about new research findings. I continue to be amazed by how much time and money are wasted by researching the obvious or studying the same treatments over and over again.

After all, how many times do we need to prove meditation can reduce fibromyalgia pain? Didn’t we figure that out years ago?

I really thought I’d seen it all until an article entitled, “The Power of Flowers May Ease Fibromyalgia Symptoms,” showed up in my inbox last month.

As I read it, I literally said out loud: “Are you kidding me?”

In case you haven’t read the article, it summarizes a recent Israeli study in which 61 women with fibromyalgia completed a 12-week flower design course presented by a trained florist. At the end of the course, Tel-Aviv University researchers reported “quite amazing” improvements in the women’s fibromyalgia symptoms.

Yep, you read that right: The researchers claim arranging a few daisies and baby’s breath in a vase actually improves fibromyalgia.

Now, I don’t doubt for a minute that flower arranging is relaxing and could have a calming effect on the central nervous system. That, in turn, could lead to a reduction in pain and other fibro symptoms.

But so could watching butterflies or painting rocks.

While I think it’s wonderful researchers are looking at non-pharmaceutical treatments for fibromyalgia, studies like this completely invalidate the seriousness of our condition. These types of studies make it seem like almost anything will fix fibro, and that is just not reality.

Because of the stigma of fibromyalgia, we already struggle to prove to our doctors and loved ones that we’re really sick. What do you think the average person is going to think when they read flower arranging helps fibromyalgia? While I’m sure the researchers had good intentions, this study makes a complete mockery and joke out of an extremely painful, life-sucking condition.

In my mind, I think back to all of those doctors who tried to give me anti-depressants and anti-anxiety medications when I complained about unexplained pain, fatigue, bladder urgency, neuropathy and a long list of other symptoms. The message was clear: “It’s all in your head. You’re just a stressed out, middle-aged woman who needs to chill out.”

What happens when these same doctors read the Israeli study? I can envision them now referring their patients to the nearest community college for classes on cupcake baking and basket-weaving. As if we weren’t frustrated enough with the conventional medical system!

The truth is we don’t need more BS fibromyalgia studies like this one. We need researchers to get serious! We need them to take a deep dive into the minds and bodies of fibromyalgia patients and figure out what causes us to feel like a three-day-old warmed over microwave dinner.

We need real solutions – treatments that get to the root cause of our illness – not a new hobby!

Donna Gregory Burch lives with fibromyalgia and chronic Lyme disease. Donna covers news, treatments, research and practical tips for living with fibromyalgia and Lyme on her blog, FedUpwithFatigue.com. You can also find her on Facebook and Twitter.

Donna is an award-winning journalist whose work has appeared online and in newspapers and magazines throughout Virginia, Delaware and Pennsylvania. She lives in Delaware with her husband and their many fur babies.