Tarantulas May Help Develop New Pain Medication

By Pat Anson, PNN Editor

Venom from a bird-catching Chinese tarantula may hold the key to medications that could someday block pain signals in humans, according to a new study at the University of Washington School of Medicine. Researchers say the oversized, hairy spiders inject a toxin into the birds that quickly immobilize them.

"The action of the toxin has to be immediate because the tarantula has to immobilize its prey before it takes off," said William Catterall, PhD, a professor of pharmacology and lead author of a study published in the journal Molecular Cell.

Catterall and his colleagues were curious how the venom works, so they used a high-resolution cryo-electron microscope to get a clear molecular view of its effect on nerve cells.

They found that tarantula venom contains a neurotoxin that locks the voltage sensors on sodium channels, the tiny pores on cell membranes that generate electric signals to nerves and muscles.

Locked in a resting position, the voltage sensors are unable to activate and the spider’s prey is essentially paralyzed.

"Remarkably, the toxin plunges a 'stinger' lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function," Catterall said. "Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilize and kill their prey."

In humans, sodium channels known as the Nav1.7 channel are essential for the transmission of pain signals from the peripheral nervous system to the spinal cord and brain.

UNIVERSITY OF WASHINGTON

UNIVERSITY OF WASHINGTON

In theory at least, drugs modeled after tarantula venom could be used to target and immobilize the Nav1.7 channel. Previous research has shown that people born without Nav1.7 channels due to genetic mutation are indifferent to pain – so blocking those channels in people with normal pain pathways could form the basis for a new type of analgesic.

"Our structure of this potent tarantula toxin trapping the voltage sensor of Nav1.7 in the resting state provides a molecular template for future structure-based drug design of next-generation pain therapeutics that would block function of Nav1.7 sodium channels," Catterall explained.

While venom-based medicine may sound impractical and more than a little creepy, it’s not unheard of. A pharmaceutical drug derived from cone snail venom is already being used to treat chronic pain. Prialt is injected into spinal fluid to treat severe pain caused by failed back surgery, trauma, AIDS and cancer. Like tarantula venom, Prialt blocks channels in the spinal cord from transmitting pain signals to the brain.  

12 Holiday Gifts on Life With Chronic Pain

By Pat Anson, PNN Editor

If you live with chronic pain or illness and want to have a friend or family member get a better understanding of what you're going through -- here are 12 books and videos that would make great gifts over the holidays. Or you can always “gift” one to yourself.

Click on the cover to see price and ordering information. PNN receives a small amount of the proceeds -- at no additional cost to you -- for orders placed through Amazon. As an Amazon Associate, we earn from qualifying purchases. 

Finding a New Normal: Living Your Best Life with Chronic Illness by Suzan Jackson

For nearly 20 years, Suzan Jackson has lived with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) — a condition she shares with two of her sons. In this book, Jackson shares what she and her family have learned about living well with chronic illness and finding a “new normal” through strong relationships, healthy emotions and finding joy in everyday life. The emphasis is on living life, not just enduring it.

War on Us by Colleen Cowles

Lawyer Colleen Cowles looks at how the war on drugs and myths about addiction have created a dysfunctional drug policy that prosecutes doctors for treating pain and stigmatizes patients for seeking relief. The U.S. has spent over a trillion dollars fighting the war and has little to show for it except some of the highest rates of addiction, overdose and incarceration anywhere in the developed world.

Ketamine Infusions: A Patient’s Guide by Berkley Jones

Berkley Jones looks at the increasing use of ketamine, a non-opioid analgesic, in treating chronic pain, depression, post-traumatic stress disorder and anxiety. This book is a useful guide if you are considering ketamine infusions and want to know how to select a provider, what to expect during infusions and possible side effects. Although primarily used to treat depression, some pain patients say ketamine is effective in treating neuropathy and CRPS.

Bitten: The Secret History of Lyme Disease and Biological Weapons by Kris Newby

Author Kris Newby began looking into the origins of Lyme disease after she was bitten by a tick and became seriously ill. Her research led her to a secret U.S. government program during the Cold War that used insects as biological weapons to spread disease. Newby believes the Lyme outbreak that began 50 years ago and has infected millions of Americans may have been the result of a military experiment gone wrong.

Vagina Problems: Endometriosis, Painful Sex and Other Taboo Topics by Lara Parker

A memoir by Lara Parker that explores — with unflinching honesty — her battle with endometriosis, a chronic vaginal condition that makes daily life difficult and sex painful. As a teenager, doctors initially dismissed Parker’s pain as “bad period cramps” and suggested her pain was psychological. She nearly checked herself into a mental institution before finally getting a proper diagnosis.

A Quick Guide to CBD by Dr. Julie Moltke

CBD won’t cure you of chronic pain, but Dr. Julie Moltke says cannabidiol can reduce pain, inflammation, anxiety and insomnia — and help make life more livable. This handbook is intended for beginners who want to learn how and when to take CBD, and are puzzled by all the hype surrounding vapes, oils, gummies and edibles on the market.

Pain Warriors by Tina Petrova

A documentary produced by patient advocate Tina Petrova that examines the poor treatment and medical neglect faced by millions of pain sufferers in North America. The film is dedicated to Sherri Little, a chronic pain patient who committed suicide after one last attempt to get effective treatment. Available on DVD or for streaming on Amazon Prime.

Together: The Healing Power of Human Connection by Dr. Vivek Murthy

This timely book by former U.S. Surgeon General Dr. Vivek Murthy looks at the importance of human connections and how loneliness affects our health and society at large. To combat loneliness, Murthy recommends spending at least 15 minutes each day connecting with people we care about and to give them our undivided attention.

Bottle of Lies: The Inside Story of the Generic Drug Boom by Katherine Eban

Wonder why that generic drug you take doesn’t seem to work? About 90% of pharmaceutical drugs are generic and most are manufactured overseas. While generics are promoted as cheaper alternatives to brand name drugs, journalist Katherine Eban found the generic drug industry rampant with greed, fraud and falsified manufacturing data — resulting in many patients consuming drugs that are ineffective or have dangerous side effects.

In Pain: A Bioethicist’s Personal Struggle with Opioids by Travis Rieder, PhD

Travis Rieder is a professor of bioethics at Johns Hopkins University who severely injured his foot in a motorcycle accident and became dependent on opioids while recovering from surgery. In this book, he shares his frustration with the healthcare system and how it often abandons patients to pain, addiction or both. Rieder serves on a CDC advisory panel that is helping the agency prepare an update of its controversial 2016 opioid guideline.

The Chronic Pain Management Sourcebook by David Drum

A comprehensive guide about chronic pain by medical journalist David Drum, who summarizes the many causes, types and treatments of pain. Drum also has tips on managing stress, anxiety, lack of sleep and depression. The book is easy to understand and would be a useful resource for family members, friends and caretakers who want to understand and help someone living with chronic pain.

A Little Book of Self Care: Trigger Points by Amanda Oswald

This well-illustrated book provides 40 simple, step-by-step exercises you can use to manage back pain, migraine and other painful conditions. Author Amanda Oswald explains how “trigger points” — small knots of muscles and connective tissue — can be relieved through self-massage and the “power of touch” without visiting a chiropractor or physical therapist.

These and other books and videos about living with chronic pain and illness can be found in PNN’s Suggested Reading section.

 

What Does Intractable Pain Really Mean?

By Forest Tennant, PNN Columnist

Many people have chronic pain. If you are over age 60, you probably have some bothersome pain from arthritis, bunions, carpal tunnel, TMJ or a neuropathy. These common conditions cause intermittent pain which may be quite bothersome.

There are some unfortunate persons, however, who have terrible, grueling pain that just won’t go away. It’s there 24/7. It’s the kind that keeps you awake and makes you feel so sick you can’t read, think or socialize, and it will force you to take cover on the couch or in bed.

The pain can be primarily located anywhere on the body such as the hip, neck or back. But when it flares you feel it “all over” and it is intense.

This constant pain means you have a primary or underlying disease or injury that has emitted and sent so much electricity to the central nervous system (CNS) that inflammation forms inside the brain or spinal cord. The brain chemicals and neurotransmitter-receptor systems (NTRS) that normally control and shut down pain become damaged and impaired. The chemicals your own body makes for pain control, as well as pain medications, ​stop working correctly because of the damage to these chemical-tissue receiving sites.

Constant pain means you ​need a program or protocol to treat your basic injury or disease. One that reduces electric impulses and helps rebuild the damage to the NTRS in your spinal cord and brain. Symptomatic pain relievers are usually a must, but they don’t treat or reverse your basic problem.

Intractable Pain Syndrome

Due to new research, we now call the constant pain condition the Intractable Pain Syndrome (IPS). It’s called a “syndrome” because of the many manifestations of the condition.

IPS is a complication of a disease or injury. To obtain some relief and recovery, every person with IPS must know the name of the disease or injury that started the pain, and the anatomic location on the body that first sustained pain. Our studies have found that many persons with IPS don’t have a diagnosis for the cause of their pain and may have even forgotten the site on their body where the pain originated.

Common causes of IPS are:

  • Adhesive Arachnoiditis

  • Reflex Sympathetic Dystrophy (RSD) or Complex Regional Pain Syndrome (CRPS)

  • Advanced Osteoarthritis

  • Genetic Connective Tissue/Collagen Disorder (Ehlers-Danlos Syndrome)

  • Traumatic Brain Injury (stroke, trauma)

  • Autoimmune Disease

There are other rare causes of IPS, including porphyria, sickle cell disease, interstitial cystitis, Lyme disease and rare genetic disorders.

Vague complaints or diagnoses about back pain, headaches, sprains, strains or “pain all over” are not specific enough to get you much relief or recovery and can’t be considered a legitimate cause of IPS. That’s why it is important to know the specific cause of your pain. What was the specific diagnosis that warranted an epidural injection, surgery or an opioid prescription?

Regardless of what caused your IPS or how long you’ve had it, your original pain site is problematic and needs to be identified. The site is generating inflammation and electricity, and could be scarred in a way that blocks the normal flow of electricity through the body.

The major goal of the IPS Research and Education Project is to bring awareness that simple chronic pain and IPS are quite different entities. A second goal is to bring recognition, prevention and treatment of IPS into mainstream medical practice at the community level. IPS must be known, recognized and treated in the ambulatory medical system like any other long-term care problem such as rheumatoid arthritis, emphysema, diabetes, asthma, or schizophrenia.

It must also be done along with physical, psychologic and pharmaceutical measures that are acceptable to all concerned parties and that don’t require high, risky dosages of abusable drugs.

Forest Tennant is retired from clinical practice but continues his groundbreaking research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

The Tennant Foundation has given financial support to Pain News Network and is currently sponsoring PNN’s Patient Resources section.  

One in Five U.S. Adults Have Chronic Pain

By Pat Anson, PNN Editor

Female, white and older Americans are more likely to have physical pain that limits their daily activities, according to a new CDC analysis that estimates about one in five adults have chronic pain.

The study, based on the 2019 National Health Interview Survey (NHIS), adds further insight into the demographic characteristics of chronic pain, a health condition that is more common than diabetes, heart disease and cancer combined.

The survey found that 20.4% of American adults had chronic pain “every day” or “most days” in the previous three months. Of those, a little over a third said they had pain that limited their life or work activities – what the CDC calls “high-impact” chronic pain.  Women (8.5%) were more likely than men (6.3%) to report this kind of high-impact pain.

The likelihood of having chronic pain varied considerably by age, race and whether Americans live in a rural or urban area. For example, only 8.5% of younger adults reported have chronic pain, compared to 30.8% of Americans aged 65 and over.

2019 NHIS SURVEY

2019 NHIS SURVEY

The survey found that whites (23.6%) were significantly more likely to have chronic pain compared to Black (19.3%), Hispanic (13.0%), and Asian (6.8%) adults.

Living in rural areas also raised the likelihood of having chronic pain. Over 28% of Americans living in rural areas said they had chronic pain, compared to 16.4% of those living in big cities.

A previous NHIS survey also estimated that 20.4% of Americans adults – about 50 million people -- have chronic pain. Of those, 20 million have high impact chronic pain.

Due to the multidimensional nature of pain and different definitions of its severity and prevalence, estimates can vary widely.  In 2011, the Institute of Medicine released a landmark report claiming at least 116 million Americans have chronic pain.

A recent study warned that middle-aged Americans are experiencing more pain than the elderly, a surprising shift in pain demographics. Researchers at Princeton University and the University of Southern California say acute and chronic pain is rising in working class and less-educated Americans under the age of 60. The findings run counter to long held assumptions that the elderly are more likely to feel pain due to arthritis and other conditions associated with old age.

“This is the mystery of American pain,” researchers reported in the Proceedings of the National Academy of Sciences (PNAS). “If these patterns continue, pain prevalence will continue to increase for adults; importantly, tomorrow’s elderly will be sicker than today’s elderly, with potentially serious implications for healthcare.”

Lancet Study Calls for Improvements in Pediatric Pain Care

By Pat Anson, PNN Editor

An international study by The Lancet has found that childhood pain often goes untreated, unrecognized and poorly managed, leading to chronic pain, disability and other negative consequences in adulthood.

The report by the Lancet Child and Adolescent Health Commission, led by the Centre for Pain Research at the University of Bath, found that too many children live with pain — even in developed countries — and calls for improvements in pediatric pain care, including diagnosis, pain management, social support and psychological treatment.

"Among health-care professionals, it is easy to agree that no child should experience pain if that pain can and should be prevented, avoided, or successfully treated,” said lead author Emma Fisher, PhD, a Versus Arthritis fellow at the University of Bath.

“In practice, however, we know there is ample evidence that children frequently experience preventable pain, and that in high-income settings, with advanced health-care systems and highly educated and regulated health professionals, children and young people experience pain that often goes unnoticed, unreported, or is not responded to, across healthcare including in the Emergency Department, post-surgical care, and in tertiary care.”

Childhood Pain ‘Swept Under the Carpet’

The report provides several examples of childhood pain not being recognized or treated adequately, such as what happened to Caitriona Roberts of Belfast, Northern Ireland. At age 12, she went to her doctor with pain and swelling in her ankle. Initially written-off as 'just a sprain' that would go away, she would spend the next six months living in almost constant pain, until she was referred to a specialist who diagnosed her with juvenile idiopathic arthritis, an autoimmune condition.

Now 28, Roberts has learned how to live and manage the disease. She helped researchers prepare The Lancet report.

"I think this issue has been swept under the carpet for too long. Still today, over 15 years on from my diagnosis with arthritis, I find people, including medical professionals, unaware of the condition or its effects on my day-to-day life. And when I speak to other young people, I find that sadly, very little seems to have changed in terms of how they experience pain or the support they receive,” Roberts said.

Researchers say up to 10% of young people experience chronic pain into early adulthood, with conditions such as arthritis, other types of musculoskeletal pain, recurring abdominal pain, and headaches.  

"This really matters, both for those experiencing pain and those around them but also across wider society. We know that chronic pain experienced in childhood is likely to feed through to adulthood and this has long-term health and economic costs associated,” said Fisher.

She called on providers and policymakers “to sit up and listen to the fact that too many of our young people are in pain and need help."

Myths About Opioids

One obstacle to getting that help is the stigma associated with opioid pain medication, particularly in the United States and Canada, where researchers say guidelines intended to control opioid use in adults are being “inappropriately applied to young people.”

“Substance use disorders and pain medication are both conflated in policy and in the media's portrayal of the North American opioid crisis,” the report found. “Through this media, public views have been influenced to consider opioids as drugs of addiction rather than pain medicine.  

“Health-care professionals, young people, and parents continue to hold misconceptions and believe myths about opioid use in pediatric patients, whereby the media depicts opioids as the villain and the underlying reason for substance misuse. Opioids have their place in pediatric pain medicine. In the context of the oversupply of opioids, childhood pain can usefully be considered a risk factor for long-term harmful exposure to opioids.”

More Than Growing Pains

The report found that improvements in pediatric pain care have come slowly. The last major intervention in the field came in the 1980’s, when it was recognized for the first time that babies experienced pain. Up until that point, a number of routine and major operations, including heart surgery, were carried out on babies without anesthetics.

"Parents tell us about the struggle they have convincing their GP that their child's illness is more than growing pains,” said Zoe Chivers, Head of Services at Versus Arthritis, which funded the report. “While the focus, attention, and dedication in providing quality services to children is consistently in place for conditions like cancer it's woefully absent for childhood arthritis and chronic pain.

"As a society we need to understand that dismissal of arthritis comes at high price and that adults and children living in pain with the condition should no longer be expected to pay it."

The study has four key goals: to make childhood pain matter, to make it understood, to make it visible, and to make it better. One recommendation is to make routine vaccinations less painful and stressful for children, such as allowing parents to be present during the injections and using topical analgesics.

"For many parents and children, a trip to the doctors for routine inoculations will be a stressful and painful experience. This does not have to be the case - we know how we can make the experience less painful for young people, but we're not doing it. This is just another example of how pain has been accepted as an everyday feature of growing up," said Fisher.

COVID-19 Research Could Lead to New Painkillers

By Pat Anson, PNN Editor

A loss of taste or smell is one of the early signs of being infected with COVID-19. Scientists say the virus appears to bind itself to nerves in the nasal cavity, causing inflammation that blocks sensory signals associated with smell and taste from reaching the brain.

Researchers at the University of Arizona believe SARS-CoV-2 may have a similar effect on pain signals and essentially acting as an analgesic. That may explain why nearly half the people infected with COVID-19 experience few or no symptoms, even though they are still able to spread the disease.

"It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you're walking around all fine as if nothing is wrong because your pain has been suppressed," says Rajesh Khanna, PhD, a pharmacology professor at UArizona Health Sciences College of Medicine Tucson.

"You have the virus, but you don't feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that's of enormous value."

Viruses cause infections by attaching themselves to protein receptors on cell membranes. Early in the pandemic, scientists established that SARS-CoV-2 enters the body via the ACE2 protein on the surface of many cells. Recent preliminary studies suggest there is another route to infection, in which the virus attaches itself to a receptor called neuropilin-1.

"That caught our eye because for the last 15 years my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin," said Khanna. "So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing."

How COVID-19 Blocks Pain Signals

Many biological pathways send pain signals to the brain. One is through a protein called vascular endothelial growth factor-A (VEGF-A), which plays an essential role in blood vessel growth but also has been linked to inflammatory diseases such as rheumatoid arthritis and osteoarthritis. VEGF-A binds to neuropilin in a way that triggers a cascade of pain signals.

In research on rodents, Khanna says his team found that the SARS-CoV-2 binds to neuropilin in exactly the same location as VEGF-A, which “completely reversed the VEGF-induced pain signaling." The virus had an analgesic effect at both high and low doses.

Khanna and his colleagues’ groundbreaking research has been published in the journal PAIN. He also authored a blog post in the Daily Beast to explain the findings in layman’s terms. He says the discovery could not only lead to new treatments for COVID-19, but new ways to block pain signals.

“Sneaky virus, fooling people into believing that they do not have COVID-19. But, ironically, it may be gifting us with the knowledge of a new protein, critical for pain. Two roads emerge in the forest ahead: (1) block neuropilin-1 to limit SARS-CoV-2 entry, and (2) block neuropilin-1 to block pain,” Khanna wrote in the Daily Beast.

In future studies, Khanna say his research team will be examining neuropilin as a new target for non-opioid pain relief. They have already tested existing neuropilin inhibitors developed to suppress tumor growth in cancers and found they provided the same pain relief as SARS-CoV-2 when it binds to neuropilin.

"We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief," Khanna said. "We have a pandemic, and we have an opioid epidemic. They're colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic."

American Mystery: Why Do Middle-Aged Adults Have More Pain?

By Pat Anson, PNN Editor

A provocative new study is warning that middle-aged Americans are experiencing more acute and chronic pain than the elderly, a dramatic shift in pain demographics that is putting further strain on the U.S. healthcare system.

Researchers at Princeton University and the University of Southern California (USC) analyzed survey responses from more than 2.5 million people in the U.S. and European Union. They found a unique pattern in the United States: Physical pain is rising in working class and less-educated Americans under the age of 60.

The findings run counter to long held assumptions that the elderly are more likely to feel pain due to arthritis and other chronic illnesses associated with old age.

“This is the mystery of American pain. Using multiple datasets and definitions of pain, we show today’s midlife Americans have had more pain throughout adulthood than did today’s elderly,” researchers reported in the Proceedings of the National Academy of Sciences (PNAS). “If these patterns continue, pain prevalence will continue to increase for adults; importantly, tomorrow’s elderly will be sicker than today’s elderly, with potentially serious implications for healthcare.”

Researchers Anne Case, PhD, and Sir Angus Deaton of Princeton University and Arthur Stone, PhD, a psychology professor at USC, have studied morbidity and mortality rates around the world. It was the husband-and-wife team of Case and Deaton who first reported on the so-called “deaths of despair” in 2015, an unusual spike in deaths of nearly half a million middle-aged, mostly white Americans.

To build on that groundbreaking research, Case, Deaton and Stone looked at different generations born between 1930-90. They found that men and women of all races usually reported more pain as they aged. But that finding did not hold true for less educated Americans who do not have a college bachelor’s degree – about two-thirds of the adult U.S. population.

"Our expectation was that pain would increase as one's age increases, due to physical deterioration and higher probability of chronic illnesses," said Stone. "But our research found middle-aged Americans had higher levels of pain than the elderly, which is especially pronounced for people without a college degree, and the question was, why?"

Researchers say their findings have major policy implications. As less educated, middle-aged Americans become elderly, they are likely to experience more pain, adding further strain on pain management practices and the healthcare system in general.

Many patients already feel their pain care is inadequate, due to lack of access to opioid pain medication and alternative treatments that are either ineffective or not covered by insurance.

Pain is getting worse for less-educated Americans. This not only makes their lives worse, but will pose long-term problems for a dysfunctional healthcare system that is not good at treating pain.
— Sir Angus Deaton, Princeton University

Researchers believe the rise in pain in the working class was caused by the deterioration of their social and economic conditions. Less-educated Americans born after 1950 are more likely to experience social isolation, more fragile home lives, less marriage and more divorce, as well as stagnant wages and job loss. This “epidemic of despair” has barely touched more-educated Americans.

Another explanation for the increase in pain is that people could be more likely to report minor pain than in the past. The growing number of Americans who are obese could also be contributing to the problem, because more weight increases the risk of health problems like arthritis, diabetes and cardiovascular disease.

Whatever the cause, researchers say their findings should signal to policymakers that less-educated Americans are experiencing more distress, and that tomorrow's elderly will feel more pain than today's elderly.

"Pain undermines quality of life, and pain is getting worse for less-educated Americans," Deaton said. "This not only makes their lives worse, but will pose long-term problems for a dysfunctional healthcare system that is not good at treating pain."

Report Calls for Overhaul of Sickle Cell Treatment  

By Pat Anson, PNN Editor

A new report by the National Academies of Sciences, Engineering, and Medicine is calling for major changes in the way sickle cell disease is treated in the United States, including an end to the discrimination and stigma that many sickle cell patients face while navigating the healthcare system.

About 100,000 Americans live with sickle cell disease (SCD), a genetic disorder that mainly affects people of African or Hispanic descent. SCD causes red blood cells to form in a crescent or sickle shape, which can create blockages in blood vessels that prevent the normal delivery of oxygen throughout the body. As a result, sickle cell patients often suffer from chronic pain, anemia, infections, strokes and organ failure.

Compared to other chronic illnesses, SCD has received little attention from the healthcare community, resulting in a lag in the development of new treatments. Until 2018, only one drug was approved by the Food and Drug Administration to treat sickle cell patients. Bone marrow and stem cell transplants are currently the only curative therapies for SCD.

“People with sickle cell disease show incredible resilience. They often have to become their own advocate to get the treatment and services they deserve — whether in the health care system, at school, at work, or in the community,” said Marie McCormick, MD, a pediatrician and professor at the Harvard School of Public Health, who chaired the committee that wrote the report.

sickle-cell-disease-700px.jpg

Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action calls for the National Institutes of Health to designate SCD as a “health disparity” to incentivize more research, and for the Department of Health and Human Services to fund efforts to identify and mitigate disparities in health outcomes for sickle cell patients.

Lack of Compatible Donors

Although stem cell and bone marrow transplants are the only cures for SCD, it’s often difficult to find compatible donors, especially for children who can benefit the most from treatment.

“Unfortunately, less than one in five individuals with sickle cell disease have compatible donors. Those children fortunate to have a fully matched sibling as a donor enjoy very high success rates with very few complications after transplantation,” said Enrico Novelli, MD, an Associate Professor of Medicine and Director of the Adult Sickle Cell Disease Program at University of Pittsburgh Medical Center.

“The success of the procedure decreases as people get older. For many adults living with sickle cell disease, stem cell transplantation is not an option, either because they are too ill to undergo the procedure, or because of a lack of donor,” Novelli said in an email to PNN.  

“And for those who are cured by transplantation and no longer have sickle cell disease, some challenges remain; for instance, the treatments to prepare the recipient for the donor stem cells may cause infertility, and years of exposure to the disease may leave a mark in terms of organ dysfunction and chronic pain. Thus, it may take a while for some patients to overcome their sickle cell-related chronic pain after a successful stem cell transplant.”

The report recommends that the Centers for Medicare & Medicaid Services and state Medicaid programs, as the lead insurers for most sickle cell patients, explore new payment methods to encourage and pay for coordinated care delivered by certified SCD centers. Insurance coverage is also needed to finance the cost of experimental new treatments, such as gene therapy.

The report calls for more diversity and “cultural competency training” for SCD care providers, as well as better training in managing acute and chronic pain. It also recommends that federal health agencies work with states to standardize newborn screening for SCD and to develop a national registry of people living with sickle cell disease.

Can LSD Be Used to Treat Pain?

By Roger Chriss, PNN Columnist

The well-known hallucinogen LSD may have a new use. A new study published in the Journal of Psychopharmacology found evidence that LSD exerts a “protracted analgesic effect” at low doses.

The study was performed in The Netherlands on 24 healthy volunteers. Three low doses of LSD or placebo were given to the participants, who immersed a hand in near freezing water 90 minutes and five hours after dosing to assess their pain tolerance.

Results from the “Cold Pressor Test” showed that 20 micrograms of LSD “significantly increased the time that participants were able to tolerate exposure to cold (3°C) water and decreased their subjective levels of experienced pain and unpleasantness.”

It is not clear how or why LSD increased tolerance to cold water. The study authors speculate about LSD’s various actions on serotonin receptors, but also note that “an additional or alternative explanation for the analgesic effects of LSD could be hypertension-associated hypoalgesia.”

There were side effects from LSD, even at low doses. LSD slightly raised blood pressure and increased feelings of dissociation, anxiety and somatization in the volunteers. Psychological and cognitive effects were described as “very mild.”

The study has other important limitations. The Cold Pressor Test is not a good analog for real-world acute pain. And healthy volunteers in such studies tend not to be typical of the population at large. They skew young, male, and often have prior experience with the substance being evaluated that most people do not have.

Also, these studies tend not to translate to real-world use. Recent work on LSD microdosing has found “few benefits and significant downsides.”

Findings Hyped

Unfortunately, this preliminary study has already led to hype about the analgesic potential of LSD. New Atlas called it  “an incredible, first-of-its kind trial” and Futurism reported that LSD microdoses were “as effective as opioids at treating pain.”  Interesting Engineering predicted there could be possible applications of LSD as a non-addictive pain medication.”

The Beckley Foundation, which funded the study, fed the hype with a news release that claimed the analgesic effects of LSD were “remarkably” similar to oxycodone and morphine, but without the risk of addiction.

The present data suggests low doses of LSD could constitute a useful pain management treatment option that is not only effective in patients but is also devoid of the problematic consequences associated with current mainstay drugs, such as opioids,” said Amanda Feilding, Founder and Director of the Beckley Foundation. “We must continue to explore this with the aim of providing safer, non-addictive alternatives to pain management, and to bring people in pain a step closer to living happier, healthier and fully expressed lives.”

Misunderstanding Pain Research

The Cold Pressor Test is a standard way to assess pain threshold and tolerance. But results in the test vary significantly with water temperature, and the test is not seen as a precise analog with real-world pain. As a 2016 review noted, “No single experimental model can mimic the complex nature of clinical pain.”

Pain is a biopsychosocial phenomenon involving a long chain of interactions that start with peripheral sensory nerve endings and manifest in the conscious mind. Analgesic effect can be achieved locally in nerve endings, as seen with lidocaine injections; or intermediately in the spinal cord, as seen with radio frequency ablation or spinal cord simulators; or centrally in the brain, as seen with psychoactive drugs.

Therefore, comparing analgesic efficacy is far more complex than just looking at outcomes in a simple lab-induced pain model in a handful of healthy people. The LSD study did not test its subjects with multiple substances or combinations of substances.

Further, analgesics have to be safe and effective. Safety includes understanding possible drug-drug interactions. A 2008 review noted that “lithium and some tricyclic antidepressants have also been reported to increase the effects of LSD.”

A 2019 study describes several important biochemical pathways and gene polymorphisms in LSD metabolism, possibly affecting pharmacokinetics and pharmacodynamics. The article concludes that “drug-drug interaction studies in humans are required to further assess the clinical relevance of these findings.”

Analgesics like acetaminophen have relatively few drug-drug interactions. Opioids have a number of important ones, but these are well-understood and can be controlled. By contrast, cannabis is messy. Drugs.com lists 24 major and 353 moderate interactions for cannabis. There is no such list for LSD.

Pain medication needs to be effective as well as safe and reliable. Demonstrating efficacy requires far more than a handful of willing subjects being subjected to a simulated pain experience in a laboratory setting. Demonstrating safety and reliability will require extensive testing, pharmacodynamic studies, and research on drug-drug interactions. LSD may have taken the first step toward becoming an analgesic, but there is a long road ahead.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

 

NIH Study Finds Opioids Make Birds Sing

By Pat Anson, PNN Editor

Opioid medication has been associated with many things, from reduced pain and disability to constipation, addiction and overdoses. A new study has found that opioids also make birds sing.

Researchers at the University of Wisconsin-Madison say fentanyl, a potent synthetic opioid, causes “gregarious singing behavior” in starlings that sounds a bit like modern jazz. Starlings usually sing to attract mates, but these birds sang because they felt good.

“When I listen to these birds sing, it seems as if they are enjoying themselves,” Lauren Riters, PhD, a Psychology Professor at UW-Madison told Psychology Today. “To me, it sounds like free-form jazz riffs.”

The small study by Riters and her colleagues involved a total of 14 European starlings that were injected with either a placebo or small doses of fentanyl. Their findings, recently published in the journal Scientific Reports, suggest that fentanyl reduced stress and anxiety in the birds without making them intoxicated.

We report that peripheral injections of the selective MOR (mu opioid receptor) agonist fentanyl cause dose-dependent increases in gregarious singing behavior in male and female starlings, while at the same time decreasing beak wiping, which is considered a sign of stress or anxiety. The fentanyl did not affect landings, indicating that fentanyl effects on behavior were not caused by gross deficits in motor activity,” Riters wrote.

Riters is a prolific researcher, participating in dozens of studies on the social activity of starlings, pigeons, quail, finches and other birds, much of it paid for with millions of dollars in federal grants from the National Institutes of Health (NIH).

This particular study was funded by a $338,000 NIH grant to examine “deficits in social communication.” The researchers say their findings could someday be used to treat humans suffering from autism, depression and anxiety. Not to make them sing, but to make them more social.

“Such disorders are characterized by social withdrawal and deficits in the ability to communicate appropriately in distinct social contexts. The proposed research will identify manipulations that stimulate context-appropriate social interactions, which can be used in the design of clinical interventions in humans with context-specific deficits in social communication,” the UW-Madison grant application states.

Some may scoff at her research, but Riters says there are lessons to be learned from it because songbirds, like humans, are social animals that enjoy singing for the same reasons we do: It helps us feel better.

“If this is the case, it would mean that our studies on songbirds are revealing an ancient, evolutionarily conserved neural circuit that regulates intrinsically rewarded social behaviors across many animals,’ she said.

Genetic Studies Could Pave the Way to New Pain Treatments

By Dr. Lynn Webster, PNN Columnist

Millions of Americans order DNA test kits to determine their ancestries. Knowing where you come from can be entertaining.  However, DNA testing can also help identify your risk of developing some diseases, including chronic pain.

Prenatal testing for genetic disorders is common. But genetic testing is also increasingly used to determine the risk of developing certain diseases or potential responses to specific drugs.

Currently, little is known about how to use genes to make an individual more or less sensitive to pain, or to learn the likelihood that someone will respond in a particular way to an analgesic based on their genetics. The good news is that we are on the cusp of gaining more information about the genes that control pain and pain treatments, and that knowledge should allow us to develop targeted pain therapies.

Most physicians still believe that everyone experiences pain in the same way. Research recently published in Current Biology discovered a gene—the so-called "Neanderthal gene"—that is associated with increased sensitivity to pain. Recognizing that a mutation of a specific gene can influence pain perception may be illuminating for many members of the medical profession.

The Individuality of Pain

Pain specialists have known for a long time that given the same stimulus, some people feel more pain than others. The truth is, there are several genes besides the Neanderthal gene that determine how an individual experiences pain. Some genes increase our sensitivity to pain, while other genes decrease it. Some genes influence how pain is processed, while other genes determine an individual's response to an analgesic.

The ability for an analgesic to provide pain relief in an individual is partially determined by the genetics of the receptor to which the pain medication binds. These genes are different from pain-sensitivity genes. For example, oxycodone may be very effective in relieving pain for one individual, but only partially effective for another.

Optimal pain relief requires recognition that each individual responds uniquely to a given analgesic. Doctors are beginning to provide gene therapy for cancer patients. Advancements in research may someday allow us to do the same for patients with pain.

The array of pain responses to the same stimulus is a major reason why one-size-fits-all dosing of pain medications is flawed. A given dose may leave some patients undertreated and others over-treated. Unfortunately, regulators who set arbitrary dose limits fail to understand or consider this biologic variability. 

Differing clinical responses to pain stimuli and medications underscore the need to individualize therapy. Knowing more about the biology of pain can help us to understand each individual’s response to painful stimuli and the variable response to any therapy.

The Heredity Nature of Pain

How we experience pain is a result of both environmental and genetic features. The genetic factors are what we inherit. Environmental factors — which we develop rather than inherit — include cultural attitudes, emotions, and individual responses to stress. Our personality and life’s experiences are included in the environmental factors that contribute to our experience of pain. Therefore, pain is a result of genetic and environmental interactions. Both can make an individual more or less sensitive to stimuli or analgesia. It is a complex and dynamic process.

The so-called Neanderthal gene is not a new discovery but was newly recognized in Neanderthals. The discovery is interesting, because it implies the gene has an evolutionary purpose. The gene is known as SCN9. There are several pain syndromes associated with the genetic mutations of the SCN9 gene, including some types of back pain and sciatica. Mutations of this gene can result in the total absence of pain or a heightened pain expression. The type of mutation determines the phenotype (or personal characteristics) of our response to a painful stimulus.

The Genetics of Analgesia

It is unclear how Neanderthals benefited biologically from increased pain sensitivity. As we know, acute pain elicits an alarm and is considered protective. It teaches us to avoid dangers that can threaten our life, and prevents us from walking on a broken leg until it heals sufficiently to bear our weight.

Evolution may not have been concerned about the effects of chronic pain. The Neanderthals' limited life expectancy, and the fact that their survival depended on strong physical conditioning, may have made chronic pain a non-issue. Chronic pain may have made survival difficult, or even impossible, for the Neanderthals.

The recent discovery that Neanderthals had the SCN9 gene should not be surprising, given the fact that modern humans shared a common ancestor with Neanderthals. The Neanderthal gene study is of particular interest to me, because I am working with several companies that are exploring potential drugs to affect the function of the SCN9 gene. The companies have different approaches, but they all are trying to find a way to dial down an individual's sensitivity to painful stimuli.

Since the SCN9 gene can be responsible for the total absence of all pain, as well as several extreme forms of pain, it may be reasonable to target the SCN9 gene to modulate pain.

My hope is that manipulation of the SCN9 gene will reduce pain sensitivity, making it easier to control pain by adjusting the dose and type of drug we prescribe.

It is possible one or more drugs that target the SCN9 gene will be available within the next 4-6 years. If that occurs, it could be game changer for people in pain. We can then thank our Neanderthal ancestors for the evolutionary gift. 

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

Neanderthal Gene Makes Us More Sensitive to Pain

By Pat Anson, PNN Editor

The popular image of Neanderthals is that they were brutish and primitive hunter-gatherers who scratched out an existence in Eurasia 500,000 years ago. That may be a bit unfair. Anthropologists say Neanderthals were more intelligent than we give them credit for, lived socially in clans, and took care of each other. They also co-existed for tens of thousands of years with modern humans, competing for food and sometimes interbreeding before the Neanderthals were driven to extinction.

Neanderthals may have had the last laugh though, because we’ve inherited a gene from them that makes some of us more sensitive to pain, according to a new study published in the journal Current Biology. The gene affects the ion channel in peripheral nerve cells that send pain signals to the brain.

“The Neandertal variant of the ion channel carries three amino acid differences to the common, ‘modern’ variant,” explains lead author Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology in Germany. “While single amino acid substitutions do not affect the function of the ion channel, the full Neandertal variant carrying three amino acid substitutions leads to heightened pain sensitivity in present-day people.”

Zeberg and his colleagues say about 40% of people in South America and Central America have inherited the Neanderthal gene, along with about 10% of people in East Asia. Using genetic data from a large population study in the UK, they estimate that only about 0.4% of present-day Britons have the full Neanderthal variation of that specific gene.

“The biggest factor for how much pain people report is their age. But carrying the Neandertal variant of the ion channel makes you experience more pain similar to if you were eight years older,” said Zeberg.

The Neanderthal ion channel in peripheral nerves is more easily activated by pain, which may explain why modern-day people who inherited it have a lower pain threshold. Exactly how the gene variation affected Neanderthals back in the day is unknown.

“Whether Neandertals experienced more pain is difficult to say because pain is also modulated both in the spinal cord and in the brain,” said co-author Svante Pääbo. “But this work shows that their threshold for initiating pain impulses was lower than in most present-day humans.”

It’s possible the heightened sensitivity to pain acted as an early warning system for Neanderthals, alerting them to injuries and illnesses that needed attention. Neanderthals lived a hard life. About 80% of Neanderthal remains show signs of major trauma from which they recovered, including attacks by bears, wolves and other large animals.

Neanderthals made extensive use of medicinal plants. The remains of a Neanderthal man in Spain with a painful tooth abscess showed signs that he chewed poplar tree bark, which contains salicylic acid, the active ingredient in aspirin.  

Newly Discovered Blood Cells Predict Rheumatoid Arthritis Flareups

By Pat Anson, PNN Editor

A simple blood test could give an early warning to rheumatoid arthritis sufferers that their symptoms are about to get worse, according to a new study published in the New England Journal of Medicine.   

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. The symptoms come in waves, with periods of remission interspersed with painful flareups.

Researchers at Rockefeller University have identified a new type of cell – called "PRIME cells" – that dramatically increase in the blood of RA patients a week before a disease flareup.

“If we can reliably identify these new cells in patients, we may be able to tell them ‘You’re about to have a flare,’ so they can prepare themselves,” says lead author Robert Darnell, MD, a neuroscientist at Rockefeller’s Howard Hughes Medical Institute. “This would make flares less disruptive and easier to manage.”

Over a four-year period, researchers analyzed hundreds of blood samples from four RA patients, who collected the blood at home using finger pricks and sent them to Darnell’s lab. Each participant also kept a record of their symptoms to identify when flares occurred.

National Institutes of Allergy and Infectious Diseases

National Institutes of Allergy and Infectious Diseases

Darnell and his colleagues looked for molecular changes in the blood prior to the onset of symptoms, and saw an increase in immune cells two weeks prior to a flare. That was not surprising, because the cells are known to attack the joints of RA patients.

But in samples collected one week before a flare, researchers saw an increase in cells that didn't match the genetic signature of any known type of blood or immune cell. The RNA signature of the cells resembled that of bone, cartilage or muscle cells – which are not typically found in blood.

“We were so surprised to see that the genes expressed right before a flare are normally active in the bone, muscle, and extracellular matrix -- strange pathways to find in blood cells,” said coauthor Dana Orange, MD, a rheumatologist at Rockefeller. “That really piqued our interest.”

Darnell's team named their discovery PRIME cells because they are "pre-inflammation mesenchymal" cells -- a type of stem cell that can develop into bone or cartilage. Notably, while PRIME cells accumulated in the blood before flares, they disappeared during them.

Researchers say PRIME cells have RNA profiles that are strikingly similar to synovial fibroblasts, which are found in the tissue lining of joints and are known to play a role in causing RA symptoms. In experiments on laboratory mice, fibroblasts that were removed from inflamed joints and transplanted into healthy mice caused them to become arthritic too.

Researchers are now recruiting RA patients for a larger study to confirm whether PRIME cells can predict a flare. If the cells do act as a precursor, it could lead to the development of drugs that target PRIME cells and stop flares before symptoms worsen.

“For doctors and patients, intervention before a flare up is always better than just treating symptoms,” says Darnell. “If these cells are the antecedents to joint sickness, they become a potential target for new drugs.”

New Imaging Better Identifies Sources of Chronic Pain

By Pat Anson, PNN Editor

A new approach to diagnostic imaging that combines the use of positron emission tomography (PET) and magnetic resonance imaging (MRI) could help identify the causes of chronic pain better than current methods, according to a new study at Stanford University School of Medicine.

PET scans that identify increased glucose metabolism in the body – known as 18F-FDG PET -- are currently used by oncologists to detect where tumors are located. Stanford researchers say the same approach could also be used to more precisely locate inflammation in injured nerves and muscles.

"In the past few decades, we have confirmed that anatomic-based imaging approaches, such as conventional MRI, are unhelpful in identifying chronic pain generators," said Sandip Biswal, MD, an associate professor of radiology at Stanford University School of Medicine.

"We know that 18F-FDG PET has the ability to accurately evaluate increased glucose metabolism that arises from to acute or chronic pain generators. As such, in our study we examined PET/MRI as a potential solution to determine the exact molecular underpinnings of one's pain."

In the study, 65 chronic pain patients underwent 18F-FDG PET and MRI scans from head to toe. The PET/MR images were then evaluated by two radiologists to determine if more glucose uptake occurred in painful areas or in other parts of the body. Increased glucose metabolism was detected in 58 of the 65 patients.

One such patient was an adult male who lived with decades of chronic pain in his neck as a result of an injury experienced at birth. PET/MR scans — such as the image on the right — identified muscles in his right neck near a spinal nerve where there was elevated glucose uptake.

This finding encouraged a surgeon to explore the area. The surgeon found a collection of small arteries wrapped around the nerve. When the arteries were ablated (removed) by the surgeon, it relieved pressure on the nerve and the patient reported tremendous relief.

Cipriano, et al., Stanford University

Cipriano, et al., Stanford University

As a result of PET/MR imaging, 40 patients in the study had their pain management plans modified, including some who had procedures that their doctor had not anticipated, such as surgery to relieve foot pain and the placement of blood patches to treat cerebrospinal fluid leaks.

"The results of this study show that better outcomes are possible for those suffering from chronic pain," said Biswal. "This clinical molecular imaging approach is addressing a tremendous unmet clinical need, and I am hopeful that this work will lay the groundwork for the birth of a new subspecialty in nuclear medicine and radiology.”

Biswal recently presented his findings at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging. They’ve also been published in the Journal of Nuclear Medicine.

Can a Cuddly Robot Reduce Pain and Increase Happiness?

By Pat Anson, PNN Editor

A cuddly therapeutic robot – designed to look and act like a baby seal – can improve mood and reduce moderate to severe pain in people, according to a new study.

The PARO robot emits seal-like sounds and moves its head and flippers in response to being touched and spoken to. Since its introduction in Japan in 2005, the PARO has become a virtual pet for thousands of people around the world who live in places where real animals are not allowed, such as nursing homes, elder care centers and hospitals.

Since social contact between humans can alleviate pain, researchers at Israel’s Ben-Gurion University (BGU) designed a study to see if the PARO robot could have similar effects in 83 healthy young volunteers.

It’s important to note that anyone with acute or chronic pain was disqualified from participating in the study. Pain was induced in the volunteers by exposing them to a heat probe.

Those who were allowed to touch and pet the PARO rated their pain levels significantly lower than those who had no physical contact with the robot. They also reported significantly higher levels of happiness.

SCIENTIFIC REPORTS

SCIENTIFIC REPORTS

“Another possible explanation of our finding is that the interaction with PARO distracted the participants away from pain. Changing the focus of attention away from painful stimuli was shown to be efficacious in altering pain perception,” wrote lead author Shelly Levy-Tzedek, PhD, who heads the Cognition, Aging & Rehabilitation Laboratory at the Ben Gurion University.

"These findings offer new strategies for pain management and for improving well-being, which are particularly needed at this time, when social distancing is a crucial factor in public health."

To their surprise, BGU researchers also found lower oxytocin levels in those who interacted with PARO compared to those in a control group who did not meet the robot. Oxytocin is known as the “love hormone" because it is elevated in romantic partners or mothers bonding with their children -- so a lower level of oxytocin wasn't expected.

Researchers speculated in the journal Scientific Reports that oxytocin could also be a stress marker and that lower levels of the hormone may facilitate trust and sociability.

“In summary, this study indicates that social touch with PARO robot alleviates pain, increases happiness state and decreases oxytocin levels. Participants with higher perceived ability to communicate with PARO display greater pain alleviation as well as lower oxytocin levels,” researchers said.

A 2017 study also found that touching can have an analgesic effect. Young healthy couples who held hands while being subjected to mild heat felt less pain than those who were not touching or sitting in separate rooms.