Low Dose Naltrexone Being Studied as Treatment for CRPS

By Pat Anson, PNN Editor

Low-dose naltrexone (LDN) is already being used to treat a wide variety of chronic pain conditions, from fibromyalgia and interstitial cystitis to Ehlers Danlos syndrome and temporomandibular joint disorder (TMJ). Some doctors believe the drug may even be useful treating symptoms of a condition so painful it’s been called the “suicide disease.”

Soin Therapeutics, a small pharmaceutical startup based in Ohio, announced this month it has been granted orphan drug status from the Food and Drug Administration to explore using LDN as a treatment for Complex Regional Pain Syndrome (CRPS), a disorder of the nervous system that causes severe, intractable nerve pain.

"Obtaining Orphan Status from the FDA is an important milestone step for us at Soin Therapeutics. We look forward to running a large-scale clinical trial and eventually FDA approval to help patients suffering from CRPS," Dr. Amol Soin, the founder and CEO of Soin Therapeutics, said in a statement.

Currently, naltrexone is only approved by the FDA as a treatment for substance abuse. In 50mg doses, the drug blocks opioid receptors in the brain and decreases the desire to take opiates or alcohol. But in smaller doses of 5mg or less, some patients have found LDN to be a surprisingly effective pain reliever.

How LDN works is not fully understood, but supporters believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, chemicals produced by the body that reduce pain and anxiety.

It's important to note that because naltrexone is an opioid antagonist, it should never be taken with opioid medication – even in small doses -- because it may cause severe withdrawal.

"Low Dose Naltrexone has unique properties to specifically help the disease cascade of CRPS including attenuation of microglial cells involved in pain transmission, reduction of proinflammatory cytokines, antagonism of the Toll-like receptor 4 (TLR4), as well as stimulating release of endorphins which are the body's natural pain killers,” said Soin, who is a practicing pain management physician.

“Basically, this drug seems very well suited to treat several mechanisms of the disease process. All those properties would seemingly be quite helpful in CRPS patients. Best of all, this is a non-addicting and non-sedating drug that could be a new way to treat complex regional pain syndrome."

Soin Therapeutics hopes to develop a novel formulation of LDN and submit an Investigational New Drug application to the FDA before starting a clinical trial.

Because the patent on naltrexone expired decades ago, it’s a generic and cheap drug – perhaps the main reason it is not more widely used as a pain reliever. There is little incentive for pharmaceutical companies to market LDN or conduct expensive clinical trials to prove its effectiveness in treating pain.

Patients interested in trying LDN often encounter doctors who refuse to prescribe it “off label” or don’t know anything about it. The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website.

How I Learned To Live With and Manage Chronic Pain

By Beth Thorp, Guest Columnist

The CDC estimates that 50 million Americans – just over 20 percent of the adult population – have chronic pain.  About 20 million have “high-impact chronic pain,” which is defined as pain severe enough to frequently limit life or work activities. I am one of the “high-impact” ones.

For a long time, I did not believe that I had enough expertise or a unique enough story to share my experiences with pain, except with those closest to me.  But because of how often people tell me, “I don’t know how you do it!”; I began to believe that sharing my struggle to live with and manage chronic pain might help others who also suffer from it.

Like many others with severe chronic pain, I have had experience with using opioids.  Given the crackdown on doctors prescribing these medications, I felt that sharing all the other skills I use to manage my pain might be useful to other patients. 

I believe there are three aspects of our health which must be addressed if we are to have full and productive lives despite our pain. These are physical health, mental health and socialization.

Three-Part Model for Pain Management

Physical Health

When pain begins, the first and logical area to address is our physical health. It’s important to me to rely not just on pain medication, but a wide range of other modalities. These include:

• Physical therapy, including heat, ice, ultrasound, stretching, exercises, TENS

• Injections of steroids and analgesics

• Neuromodulation devices such as spinal cord stimulators

• The use of support tools, such as canes, walkers, wheelchairs, etc.

Some activities, like stretching, might be easy to incorporate into your daily life.  Exercise might take some trial and error to find types that help with pain and that you enjoy. Others, like using a wheelchair, might take overcoming the burden of stigma.   

For me, the idea of getting a wheelchair was initially out of the question.  But then my pain doctor suggested that it would be better to use one to travel in places like airports, museums and zoos so that I can better enjoy the experience, and have less pain during and afterwards.  Once I thought of it this way, it was an easier choice.

Mental Health

As my pain persisted, despite many physical and medical treatments, it became clear to me that I needed some additional resources to help my mind and spirit.  These treatments used to be considered outside of traditional Western medicine.  Additionally, these methods often require out-of-pocket payment. Some examples are:

• Counseling, talk therapy, hypnosis, Reiki

• Meditation and mindfulness

• Participation in activities designed to distract from the pain

• Antidepressant medications

• Focusing on the positive

There are other therapies which address both physical and mental health, including yoga, Pilates, acupuncture, therapeutic massage and tai chi. 

I rely more on distraction than on any other technique.  If one activity does not work, then I will go to another.  When I first heard about distraction, I did not believe that it would work -- but it really does.  Even getting out of one environment into another can help. 

I am still working on the technique of focusing on the positive rather than the negative.  I know this sounds a bit Pollyanna, but I believe it is important to move ahead with a good quality of life.  The goal is to be grateful for the things I can do, not ruminating on the things I have lost or can no longer do. Some examples of this are:

• Take “one day at a time.”  If today is bad, tomorrow is likely to be better

• Try new activities that fit within the scope of your current abilities

• Learn new skills or explore new areas to learn by taking classes, in person or online

• Find others who suffer from chronic pain and share ideas for living better

• Most of all, don’t give up! 

Socialization

The longer pain goes on, the more isolating it can be. I’ve experienced loneliness and solitude. Our world gets smaller as the number of things we can do shrinks and the things we can do become very restricted. 

One of the hardest things for many of us is to ask for help. Similarly, we don’t want to be a burden, so we don’t reach out to ask our friends and family to come over and spend time with us. 

In order to maintain a good quality of life, we must find our own ways to become or stay involved with others.  For example:

• Phone calls or Skype, FaceTime and Zoom meetings with family and friends

• Group activities such as book clubs, crafting circles, games nights, group lunches

To address mental health as well as socialization, joining a religious group, community organization or chronic pain support group can be very helpful.  You can also combine socialization and physical health with activities such as exercise classes or Silver Sneaker programs.

Three Changes Needed

I believe that there are three changes to our healthcare system which must be pursued in order to respond to the opioid crisis in ways that help patients with pain, not hurt them.

First, don’t punish patients by removing access to opioid medications. For some of us, they are the only thing that works. Work with us to help us take them responsibly. 

Second, the pharmaceutical industry should develop safe, effective and non-addictive pain medications for those of us with high impact chronic pain. 

Third, insurance companies should be required to pay for alternative treatments such as massage, acupuncture, yoga, etc. that are often recommended as alternatives to opioids. Those options are not really available to most patients with pain.

Chronic pain may last a lifetime.  Thus, it is critical to find ways to live a full and happy life despite the pain.  Different methods work for different people.  I believe that the most important thing is to try everything you can.  If one doesn’t work, try another.  Be sure to include physical, mental and social solutions.  And try to stay as positive as possible.  That’s how I do it.  You can do it too! 

Beth Thorp has lived with chronic pain from sciatica, neuropathy and osteoarthritis for almost 25 years. She’s had multiple back surgeries, including two implanted stimulators.

Beth worked for 34 years in the pharmaceutical industry, including as a partner in her own consulting firm. She is now retired and spends her time with her family, as well as knitting, quilting, reading and exercising.

PNN invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org

How Pacing Can Stop the Boom-Bust Cycle of Pain

By Gabriella Kelly-Davies, PNN Columnist

Many people living with chronic pain are stuck in a boom-bust cycle. I was one of them until I took part in a multidisciplinary pain management program and learned how to pace my activities and exercises.

On the good days when our pain level is low, we try to catch up on doing all the things we couldn’t do when the pain was bad the previous day. But this can cause a flare-up and the natural response is to rest or take a pain medication. Once the pain eases, we might try again, only to repeat the pattern of overactivity, flare-up, rest, easing of pain, then overactivity.

When this happens repeatedly, we can become frustrated and despair of ever being able to live a normal life. It becomes difficult to plan ahead because we never know how we will be on any day. Over time, there are fewer good days and more bad days and we feel as if we have lost control of our life. We become so afraid of causing a flare-up that we avoid any activity that aggravates our pain.

The end result is that our bodies lose conditioning and become less able to cope with a higher level of activity. Muscles weaken, joints stiffen, and less and less activity causes a flare-up.

The good news is that we can use a pain management technique known as pacing to increase our activity levels without stirring up the pain. Pacing involves starting at a level of activity that doesn’t aggravate our pain, breaking up tasks into smaller steps, gradually increasing the amount we do, and taking frequent, small breaks. Over time, it is possible to increase our tolerance to a range of daily activities and exercises. 

Set Goals and Build Up Gradually

Pacing can be applied to everything you do. If sitting increases your lower back pain, try to use pacing to build up your sitting tolerance. You can also pace exercises such as walking and swimming, and use it to increase your tolerance to activities such as housework, gardening and driving.

The first step is to decide which activities or exercises are your priorities, then determine your baseline tolerance to them. A starting point 20 percent below your current level is a general rule of thumb. If sitting exacerbates your lower back pain, determine how long you can sit comfortably. If you can sit for five minutes without triggering a flare-up, set your baseline at 80 percent of five minutes, which is four minutes.

Once you know your baseline, set short and long-term goals and record them in a chart. Each day, increase the time you do the activity or exercise by a predetermined small amount.

If your long-term goal is to sit and watch a movie for two hours without causing a flare-up and your baseline is four minutes, your short-term goal might be to increase your sitting by one minute each day. At the end of the week if you can sit comfortably for 10 minutes, you can repeat this pattern for the following weeks until you reach two hours. However, if you find that increasing by one minute every day stirs up your pain, try increasing by one minute every second or third day.

Record your progress in a chart like the one below so you can see how much you are building sitting tolerance.

SHORT-TERM GOALS

SITTING PROGRESS

Break Up Activities

Pacing also involves breaking up tasks into smaller amounts that don’t cause a flare-up. If carrying heavy bags of groceries from the supermarket exacerbates your back pain, try buying smaller amounts of groceries more often. For example, go to the supermarket three times a week and buy small amounts rather than doing one big shop each week.

Taking short and frequent breaks is another way of gradually building up your tolerance to an activity. For example, if you can weed your garden for 10 minutes without flaring up your pain, make your baseline 80 percent of 10 minutes, which is eight minutes. Work in the garden for eight minutes, rest for 15 to 30 minutes, garden for another eight minutes, rest for 15 to 30 minutes, and so on. During your rest period, it’s a good idea to practice your relaxation exercises and stretches.

As your tolerance to gardening increases, you can gradually build up the time you garden before you rest.

Fine-Tuning Your Plan

Pacing is a process of trial and error, and your initial goals might need to be fine-tuned if you find that pain interferes with you achieving them. Try to be patient and don’t overdo it. It’s better to take baby steps and achieve your goals than to race ahead and fall back into the boom-bust cycle.

It’s crucial you stick with your plan each day. If you are having a good low-pain day, don’t be tempted to increase each activity for longer than the predetermined time because you might risk flaring up your pain. On the other hand, if you are having a bad day, try to stick with your goals for the day, but take brief breaks and do your relaxation exercises and stretches during the breaks.

Pacing is an important part of an armory of pain management strategies. Like other multidisciplinary pain management approaches, it takes time to learn, but once you master the technique, it will put you in control of your day rather than your pain level dictating what you can and can’t do.

By keeping to your plan in a disciplined way, you will gradually build up your tolerance to activities of daily living and leisure. With practice, you, rather than your pain level, will determine how much you can do, giving you more control and a better quality of life.

Gabriella Kelly-Davies is a biographer who lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Pain Desensitization: How to Overcome Fear of Chronic Pain

By Gabriella Kelly-Davies, PNN Columnist

Something common to us all is a dislike of pain. Sudden or acute pain is a warning signal that something is wrong. When it strikes, we try to escape from it by taking a pain reliever, distracting ourselves, resting or seeing a health professional.

This approach usually works after an injury or surgery while waiting for the damaged tissues to heal and the acute pain to settle. But it is not as effective for chronic pain when the cause of the pain is a malfunction in the processing of pain signals in the central nervous system, rather than tissue damage.

While chronic pain is not generally a warning sign, the brain may still see it as a threat. It prompts the same avoidance behaviors we use for acute pain. Many people living with chronic pain are so fearful of triggering a flare up, they avoid anything they believe exacerbates their pain. This fear can be so intense it prompts them to leave the workforce prematurely, stop doing usual daily activities such as shopping and housework, and give up doing all the things that previously gave them pleasure.

Australian psychologist Michael Nicholas, PhD, was worried that many of his patients at the Michael J. Cousins Pain Management and Research Centre in Sydney limited their daily activities to avoid pain. Some patients even tried staying in bed all day to prevent provoking their pain.

Nicholas wondered whether an exposure technique used by psychologists to treat phobias such as fear of heights could be applied to pain management. In exposure therapy, psychologists create a safe environment, then gradually expose an individual to the thing they fear. With repeated exposures in a safe environment, anxiety and fear can be reduced.

“I thought exposure therapy might reduce the fear of pain and the resulting avoidance behaviors,” Nicholas told me. “This would mean training the brain to learn not to react to chronic pain. I started encouraging my patients to sit quietly for 20 minutes, acknowledge their pain, but not react to it. After doing this repeatedly over a few weeks, many patients told me their pain was still there, but they were no longer so bothered by it. They lost the urge to escape from it.”

Nicholas described the technique as pain desensitization because his patients were familiar with the idea of pain sensitization, and he thought this could be a way of countering that effect.

For the last few decades, Nicholas and his colleagues have used this approach in the multidisciplinary pain management programs at their center. As with learning any new skill, he says mastering pain desensitization takes a lot of practice.

“You’ve got to practice pain desensitization regularly,” Nicholas explained. “Often people aren’t prepared to do that.” He likens it to lifting weights at the gym to build up muscle strength, something that usually takes weeks or even months.

“If you’re trying to change the way your brain responds to pain; you’ve got to do a lot of workouts. It can take up to two to three months of daily practice to master pain desensitization. But once you get the hang of it, it reduces the distress caused by your pain.”

I learned pain desensitization in 2008 in a three-week pain management program. It took me several weeks of twice-daily practice to fully grasp it, but I soon incorporated it into my usual routine. For years it has been a seamless part of my day, and I practice it regularly, especially when I have a flare-up.

Learning Pain Desensitization

Try making pain desensitization a part of your daily relaxation practice. Close your eyes, take a deep breath and let it out slowly, focusing your mind on breathing calmly. After a couple of minutes of gentle breathing and relaxing, turn your attention to the pain. If you have several painful sites, choose one of them.

While focusing attention on the pain, try not to think about how bad it is. You can’t stop yourself from thinking, but you don’t have to respond to the thoughts. Just let thoughts pass you by like a leaf floating on the stream. Calmly focus on the sensation you call pain and see what happens. Don’t try to change the pain or attempt to make it go away because that is trying to escape from it. Simply let it be there and continue relaxing.

Sometimes the pain might start to feel worse because you are used to trying to escape from it. If this happens, continue with your breathing exercises and any increase in pain will settle. Try to observe your pain as calmly as possible, almost as if it is in someone else’s body. Or imagine you are doing a scientific experiment and focus on the pain like a scientist might observe a leaf or a bug under a microscope. Be as objective as possible, without reacting emotionally to it.

If your mind wanders, bring it gently back to focusing on the pain. Continue relaxing and use your breathing exercises to calm yourself. Keep this up for about 15 to 20 minutes and see what happens. Look at it as a type of experiment and evaluate what you notice. Remember, you’re just allowing yourself to experience the pain that will be there anyway, even if sometimes masked by medications. You aren’t doing anything that can harm you.

By allowing yourself to feel the pain repeatedly, you can habituate to it, because our brains naturally habituate to repetitive stimuli. This effect is similar to what happens when you put a new painting on your living room wall. At first, you notice it whenever you walk past it. But after a while you notice it less. You remain aware that it’s there, but you don’t notice it as much.

Don’t expect too much too soon. Just keep practicing because eventually you will retrain your brain to not respond with alarm to the pain. You’ll find that as you get better at desensitizing, you also become more relaxed when feeling your pain.

Once you have learned the technique, try it whenever your pain starts to trouble you, particularly during exercise or other activities that aggravate your pain. If pain stops you from falling asleep, try desensitizing in bed at night.

Start with a mix of long and short sessions -- two or three 20-minute sessions each day. In between, try brief sessions of one to two minutes whenever you notice your pain or when exercising. After a few weeks it will become a habit and you’ll find yourself doing it without realizing it.

Pain desensitization isn’t a miracle cure for chronic pain. Instead, it is one of the many techniques used in multidisciplinary pain management programs to modify the experience of pain. Importantly, it helps people reduce the impact of pain on their life.

“You have to see it as a training exercise, not as a gimmick,” Nicholas advises. “It’s a skill you’ve got to learn, like learning to play tennis. But as with tennis, once you’ve mastered it, you’ll find you do it automatically without thinking. Many people are surprised by how effective it can be for reducing the distress caused by their pain.”

Gabriella Kelly-Davies is a biographer who lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Fibromyalgia Patients Needed for Online Therapy Study

By Pat Anson, PNN Editor

A digital therapeutics company is looking for volunteers to participate in a clinical trial to see if smartphone-based therapy can improve symptoms of fibromyalgia.

Swing Therapeutics recently announced that its acceptance and commitment therapy program (ACT), a form of cognitive behavioral therapy (CBT), has received Breakthrough Device Designation from the Food and Drug Administration. CBT is a form of psychotherapy, in which patients are encouraged to reduce unhelpful thinking and behavior.

“Currently, most people living with chronic pain conditions like fibromyalgia are offered medications and some suggestions for modifying their lifestyle. Behavioral therapies have evidence supporting their effectiveness for pain management, but are not widely available or easily accessed by the average individual,” said David Williams, PhD, Associate Director of Chronic Pain and Fatigue Research Center at the University of Michigan, who is an advisor to Swing Therapeutics.

The company says a pilot study of its online therapy program has shown promise in managing fibromyalgia, a poorly understood disorder characterized by widespread body pain, fatigue, poor sleep and depression. The self-guided daily program includes interactive lessons and exercises designed to help fibromyalgia sufferers understand, accept and manage their symptoms. The core program lasts 12 weeks, followed by a maintenance phase for extended use.

Swing is looking for 500 participants in the U.S. who are at least 22 years of age and have a diagnosis of fibromyalgia. The digital therapy program can be conducted at home, with no in-person medical visits or medications required.  Participants will receive compensation after completing surveys at the end of the 12-week program. Click here to learn more about the study.

“Our team is committed to creating valuable digital therapies and demonstrating strong clinical evidence to support their use. The results of our initial studies are encouraging, and with the support of the FDA, we look forward to optimizing the product as we advance through our pivotal trial,” said Mike Rosenbluth, PhD, founder and CEO of Swing Therapeutics.

The FDA has approved only three drugs to treat fibromyalgia: the antidepressants duloxetine (Cymbalta) and milnacipran (Savella), and the anti-seizure medication pregabalin (Lyrica). Many patients say the drugs are ineffective and have side effects. A recent analysis found little evidence to support the long-term use of any medication or therapy to treat fibromyalgia.

Electro-Medical Therapy Can Help Treat Intractable Pain

By Forest Tennant, PNN Columnist

To maximize relief and recovery from Intractable Pain Syndrome (IPS), it is advisable to employ one or more electro-medical (EM) therapies. All persons with IPS are highly encouraged to try a variety of EM therapies, but only as an adjunct or add-on to their current medical treatment.

Electric Current Devices

Electric current (EC) therapy is probably the best known of the EM therapies. Electric currents primarily have an anesthetic effect, much like a local anesthetic such as lidocaine. They anesthetize nerves or spinal cord nerve roots and provide temporary pain relief. In some cases, EC therapy may even bring about long-term pain relief because electric currents sometimes reset electrical conduction of nerves.

EC devices can vary, like light bulbs, in power and frequency. One advance is called “micro current.” This is a low power frequency in which the current can be transmitted through the earlobe or scalp to treat headaches or central pain.

Electric currents of various powers and frequencies are now combined in products and devices such as transcutaneous electrical nerve stimulators (TENS units), Calmare “Scrambler” therapy, and spinal cord stimulators. Devices with multiple currents usually bring a superior result compared to a single current device.

Unfortunately, only a therapeutic trial will tell you which EC therapy will help you. Many self-help TENS units are available for home use, and they should be tried. All persons who have IPS from a stroke or traumatic brain injury should consider a trial with micro-current therapy.

If you find an EC device that gives you relief, don’t use it every day. As with drugs, you may become tolerant, and the device will become ineffective. Give at least a day between treatments.

Electromagnetic Devices

Electromagnetic (EMT) devices are new to pain treatment and are quite different from EC devices because they use energy that is 50% electric and 50% magnetic. The energy is comprised of sub-atomic particles not usually visible to the naked eye.

EMT energy is generated by devices that manipulate the electric current that is found in every battery or household electrical socket. The energy is condensed into a wave that can be sent into human tissue with a transmitter wand, probe or plate. The energy wave can be administered in different frequencies and wave lengths that vary from a very slow, long wave to a very fast, short wave.

The three major types of EMT are laser, infrared and radio. Infrared is a low-frequency long wave, while radio has long, slow waves. Lasers can put out infrared waves, and also emit visible high energy frequencies which can cut, dissolve or ablate tissue.

In medical administration, long slow waves may penetrate several inches into the human body, while the short high frequency waves of laser and infrared will not normally penetrate human tissue by more than an inch. Some devices pulse the waves to get deeper tissue penetration. These devices are known as “Pulsed Electromagnetic Energy Frequency“ or PEMF.

Lasers may be able to totally remove or dissolve a pain “trigger.” For example, an experienced practitioner may be able to identify a pain trigger along the spine, or neuropathy in the face or extremity, and actually cure the condition with laser treatment.

Infrared is the most effective EMT for pain relief of a recent injury to the spine, joint or soft tissue. It is quite effective for contusions or joint swelling. Infrared can also help drive medication through the skin, so it is very effective if a cortisone cream is applied to the skin during infrared treatment.

Radio waves penetrate deeply. Their best use appears to be for spinal conditions, including herniated discs and other spinal inflammatory conditions, such as arachnoiditis. Deep penetrating radio waves will probably, at least in some cases, reach the interior of the spinal canal.

Major Take Home Point

Patients with IPS are constantly bombarded with the pitch that they need an electromagnetic “savior” such as an implanted electrical stimulator, or an expensive multi-electric current or electromagnetic course of treatment. The parties who sell and promote these devices are invariably unknowledgeable about the serious, relatively rare condition of IPS.

EC and EMT devices are made for acute or short-term pain and injury problems, not constant incurable pain with cardiovascular, endocrine and autoimmune complications.

Implanted electrical stimulators may be a “godsend” to some IPS patients, but they may not work or even cause more pain for others. This is why trials are done prior to implantation. The big problem is that there is so much money to be made with implanted stimulators that some unethical practitioners don’t tell you that they are mainly for breakthrough or flare pain.

There are many risks to implanted stimulators, so every IPS patient needs to remain on a 3-component medical program that combines suppression of inflammation, repair of damaged tissue and pain control.

Once you are on this 3-component protocol and have a good nutritional and physical program solidly in place, then give electromedical measures a try. Simple measures like water soaking or magnets may  also be very helpful. Electromagnetic administration is relatively new and shows great promise!

Forest Tennant is retired from clinical practice but continues his 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 gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.    

Sales Reps Assist Surgeons During Implant Operations

By Fred Schulte, Kaiser Health News

Cristina Martinez’s spinal operation in Houston was expected to be routine. But after destabilizing her spine, the surgeon discovered the implant he was ready to put in her back was larger than he wanted to use — and the device company’s sales rep didn’t have a smaller size on hand, according to a report he filed about the operation.

Dr. Ra’Kerry Rahman went ahead with the operation, and Martinez awoke feeling pain and some numbness, she alleges. When Rahman removed the plastic device four days later and replaced it with a smaller one, Martinez suffered nerve damage and loss of feeling in her left leg, she claims.

Martinez is suing the surgeon, implant maker Life Spine Inc., and its distributor and sales representatives, alleging their negligence led to her injuries because the right part wasn’t available during her first surgery. All deny wrongdoing. The case is set for trial in November.

The lawsuit takes aim at the bustling sales networks that orthopedic device manufacturers have built to market ever-growing lines of costly surgical hardware — from spinal implants to replacement knees and artificial hips commonly used in operations. Sales in 2019 topped $20 billion, though covid-19 forced many hospitals to suspend elective surgeries for much of last year.

Device makers train sales reps to offer surgeons technical guidance in the operating room on the use of their products. They pay prominent surgeons to tout their implants at medical conferences — and athletes to offer celebrity endorsements. The industry says these practices help ensure that patients receive the highest-quality care.

But a KHN investigation found these practices also have been blamed for contributing to serious patient harm in thousands of medical malpractice, product liability and whistleblower lawsuits filed over the past decade.

Some patients allege they were injured after sales reps sold or delivered wrong-size or defective implants, while others accuse device makers of misleading doctors about the safety and durability of their products. Six multi-district federal cases have consolidated more than 28,000 suits by patients seeking compensation for injuries involving hip implants, including painful redo operations.

In other court actions, patients and whistleblowers repeatedly have accused device companies of failing to report injury-causing defects to federal regulators as required — or of doling out millions of dollars in illegal kickbacks to surgeons who agreed to use their products. Device makers have denied the allegations and many such cases are settled under confidential terms.

‘Inundated With New Implants’

At least 250 companies sell surgical hardware, and many more distribute it to doctors and hospitals across the country. Spine companies alone obtained more than 1,200 patents for devices in 2018, according to an industry report. Many come to market through a streamlined Food and Drug Administration process that approves their use because they are essentially the same as what is already being sold.

“In orthopedics, we are inundated with a multitude of new implants that debut each year,” Dr. James Kang, chairman of the orthopedic surgery department at Brigham and Women’s Hospital, remarked at a Harvard Medical School roundtable discussion published in 2019.

Kang said surgeons often rely on industry “reps” in the operating room for guidance because it is “usually burdensome and difficult” for surgeons to know “all of the intricate details and nuances” of so many products.

Martinez’s lawsuit says the process went awry during her 2018 spinal fusion in Houston, an operation in which an implant is inserted into the spinal column to replace a worn or damaged disc.

Martinez was under anesthesia, with her spine destabilized, when Rahman discovered the Life Spine surgical kit did not contain any implants shorter than 50 millimeters, or about 2 inches. That was too large, according to the complaint. Martinez, a former day care worker, blames her injuries on the redo operation, which replaced the implant with a 40 mm version Life Spine supplied later.

Through his lawyer, Rahman declined to comment. In court filings, the surgeon has denied responsibility. His operating notes, according to court pleadings, say he had ordered “all lengths available” of the implant through a Life Spine distributor and its sales reps. In a June court filing, Rahman contends the “small area of leg numbness experienced by Ms. Martinez was a known complication of the first surgery … and was not the result of any alleged negligence.”

In the court filing, Rahman also argues it was “appropriate” for him to rely on the sales reps and hospital staff to “inform him as to whether all materials and equipment needed for surgery were available.”

Illinois-based Life Spine also denies blame. In court filings, it says the sales reps initially ordered a sterile kit that included only implants from 50 mm to 55 mm long, which it duly shipped to Houston.

At the time of Martinez’s operation, Life Spine was the target of a sealed whistleblower lawsuit accusing it of paying improper consulting fees and other kickbacks to more than 60 surgeons who agreed to use its wares. Court records in the whistleblower case identify Rahman as one of the company’s paid consultants, although he and the other surgeons were not named as defendants.

Life Spine and two of its executives settled the matter in 2019 by paying a total of nearly $6 million. An orthopedic surgery expert hired by Martinez for her suit faulted Rahman for not making sure he had the right gear “prior to the start of surgery,” according to his report. The expert also criticized the sales rep for failing to bring “all available lengths to the procedure or to inform Dr. Rahman that the necessary implants were not available,” court records show. The sales rep and distributor denied any blame, arguing in court filings that they “met all applicable standards of care.”

Frenzied Competition for Sales

Major device makers train a corps of sales agents, some recruited right out of college, to cultivate and work closely with surgeons — one likened the relationship to a caddy and an avid golfer. Duties can include lugging 20-pound sets of surgical hardware to the operating room, assuring it is sterile and knowing its specifications, though the reps are not required to have medical training or credentials.

Stryker, one of the nation’s top four spine implant manufacturers, spends what it calls “a significant amount of time and money” to train reps. When hired, they typically “shadow” other reps for three to six months, then attend a 10-day intensive “Spine School” and other training. In all, the company said in a court filing, it typically takes eight to 18 months, often longer, to develop “long-term relationships” with customers.

For those who do, the jobs can pay handsomely. Veteran reps who influence which brands of hardware surgeons select command salaries and bonuses that can stretch into the low six figures and beyond, court records show.

The market is so hotly competitive that device makers typically require reps to sign contracts that prohibit them from working for a rival company in the same territory for a year or more — and aren’t shy about suing to fend off raids on their staffs, court records show.

In 2019, DePuy Synthes sued an Alabama sales rep who jumped ship, blaming him for stealing away accounts “worth millions of dollars practically overnight.” An arm of health care giant Johnson & Johnson, DePuy Synthes filed at least two dozen similar suits from 2014 through the end of 2020, court records show. Most, including the case of the Alabama sales rep, have been settled under confidential terms.

Some companies have spent lavishly to poach experienced sales agents — practices that can violate business conduct laws. One allegedly paid a New York sales pro a “staggering, seven-figure signing bonus.” Another is said to have dangled an $800,000-a-year job as “director of surgeon education,” while a gambit to make inroads in the Phoenix market dubbed “Sun Devil” guaranteed a branch manager a $500,000 annual salary, court records show. Another promised a sales agent $900,000 paid out over three years.

Whistleblowers and government investigators have argued for years that so much money changing hands can lead to kickbacks or other marketing schemes that corrupt medical judgment and endanger patients. Some injury suits also have blamed sales reps and distributors for staying mum about product deficiencies they observed in the operating room. These cases often are settled with no admission of wrongdoing.

Sometimes, surgeons help promote implants at medical meetings and other gatherings. Orthopedic surgeons and neurosurgeons received a total of about $511 million in industry consulting fees from 2013 through 2019 and nearly $300 million more for “serving as faculty or speaker” at industry-sponsored events, a KHN analysis of government data found.

Dozens of lawsuits have taken aim at Indiana device maker Biomet’s advertising a hip replacement for “younger, more active patients” that showcased Olympic gold medal gymnast Mary Lou Retton. One ad says “Mary Lou lives pain-free, and so should you.” Yet Retton suffered painful heavy-metal poisoning requiring the implant’s removal and sued the company for damages, according to court records. Retton said she and Biomet settled the suit in 2019 under confidential terms.

Defects Ignored or Downplayed

Whether touted by renowned surgeons or celebrities, orthopedic surgery marketing materials stress quick improvement in a person’s quality of life. That proves true for most patients. Yet researching how often implants fail or cause life-changing injuries — and which brands have the best safety records — can be daunting.

The FDA requires device makers to advise the agency of information “that reasonably suggests” a device they sell “may have caused or contributed to a death or serious injury or has malfunctioned” in a way that could recur. The FDA posts the reports on a public website, with the caveat that they may convey “incomplete, inaccurate, untimely, unverified, or biased data.”

KHN found that thousands of malpractice and product liability lawsuits have accused device marketers of concealing or downplaying hardware defects, leaving patients and their doctors in the dark about possible risks. In many cases, these claims are bolstered by company records, or actions by state or federal regulators.

In 2019, for instance, DePuy Synthes paid $120 million to settle a lawsuit filed by 46 state attorneys general; the suit accused the company of advertising that a replacement hip it sold lasted three years in 99.2% of operations, when it knew of data showing that 7% had failed within that time. The company did not admit wrongdoing in settling the case.

British device company Smith & Nephew faces a federal civil proceeding comprising nearly 1,000 injury suits, including one that says the company “underreported and withheld” notices of malfunctions and “willfully ignored the existence of numerous complaints about [its] failures.”

An expert hired by the patients cites a company audit showing “significant adverse events” were logged from two days to 142 days late, while a corporate memo circulated among executives to push sales was titled “Milk the Cash Cow,” according to court records. Smith & Nephew has denied the allegations and in one court paper called the expert’s opinions “speculative.”

John Saltis is suing spinal device company NuVasive over its handling of his complaint that a screw holding his spinal implant in place snapped in May 2016, about 17 months after his operation.

Saltis, 68, was two hours into his workday as a toolmaker at General Electric in Rutland, Vermont, when he felt sharp pain in his neck and shoulder, bad enough to send him to the hospital emergency room. X-rays revealed the screw had broken and, according to Saltis, fractured vertebrae in the process.

Saltis said the San Diego-based device company told the FDA the incident caused no harm. But Saltis said he has lingering numbness and pain in his right hand. As a result, he said, his lifestyle has “changed dramatically.”

“I miss things like bowling and playing toss with my grandkids,” he said.

Hans Pennink for KHN

In 2019, Saltis sued NuVasive without a lawyer, hoping to show the $600 screw was defective. In a court filing, NuVasive said Saltis is arguing “the screw is defective because it broke.” That’s not good enough, according to NuVasive, which argues that Saltis must show the screw was “unreasonably dangerous” to press his claim. In late June, a federal judge agreed and dismissed the suit, though she allowed Saltis to amend his complaint, which he is pursuing. The case is pending.

A Push for Change as Pandemic Eases

As hospitals resume elective operations stalled by the coronavirus, some industry critics see an opportunity to rethink orthopedic surgery practices — from sales to tracking of injuries.

Some want to keep industry reps out of operating rooms and place tighter restrictions on their access to hospitals. They say the current system needlessly drives up health care costs and exposes patients to risks such as infection from extra people in the operating room.

Sales reps say their technical knowledge and skills make operations safer for patients and note that many surgeons enjoy the security of having them present in the operating room. Reps also say they perform tasks that hospitals would need to hire additional personnel to do, such as keeping track of device inventories.

“The industry has embedded reps into the supply chain, and it is a hard culture to break,” said Itai Nemovicher, president of the Orthopaedic Implant Co., which seeks to produce lower-cost implants.

Yet guidelines for “reentry” after covid put out by AdvaMed and the American Hospital Association say medical device reps should deliver “services, information and support remotely whenever possible.” The guidelines advise hospitals to use videoconferencing gear when it “does not compromise patient safety or privacy.”

Dr. Adriane Fugh-Berman, a professor of pharmacology and physiology at Georgetown University, said device reps are viewed as part of the operating room team even though they are there to sell products.

“That is pretty horrifying from a patient’s point of view,” said Fugh-Berman. “Relying on sales reps in the OR is appalling. We need to come up with a better system.”

Greater transparency might have helped Little Rock, Arkansas, resident Christopher Paul Bills. He sued Consensus Orthopedics, the maker of a hip implant system that he alleged failed and sent metal through his hip joint that his surgeon said in 2016 looked “as if a bomb had gone off.” An Australian registry that tracks outcomes of operations identified the implant as having a “higher number” of hip failures compared with other manufacturers, according to the suit.

Bills underwent four operations and spent more than a year in the hospital and in rehabilitation, costs borne by Medicare and private insurance.

“Mr. Bills was left with no right hip at all and his surgeon does not plan to install a replacement hip,” the suit says. Bills uses an electric scooter to get around and hopes to graduate to hand-held crutches. “Since his right leg is useless, he will require a vehicle with hand-controls to drive,” according to the suit. The company disputed Bills’ claims and denied its hip system had any defects.

The case ended in 2019 when Bills died of cancer unrelated to his operations, said his lawyer, Joseph Saunders. “He never did get justice,” Saunders said.

Kaiser Health News is a national health policy news service. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Covid Renews Interest in Radon Health Mines

By Katheryn Houghton, Kaiser Health News

Twice a year, Brian Tichenor makes the 1,200-mile drive each way from his home in Kansas to a defunct uranium mine in Montana, where he takes an elevator 85 feet below the surface to sit amid radioactive radon gas to ease the pain from his chronic eye condition.

“I found it like I think a lot of people do,” said Tichenor, 67. “It’s a point of desperation with conventional treatment.”

While radon is commonly known as a hazardous gas removed from basements, people in pain travel to Montana and pay to breathe, drink and bathe in its radioactive particles. The travelers view the radon exposure as low-dose radiation therapy for a long list of health issues.

But the Environmental Protection Agency and the World Health Organization, among others, blame the gas as the second-leading cause of lung cancer.

Although cancer doctors use radiation as a front-line treatment to destroy dangerous cells, its role in the U.S. in low doses for other ailments is disputed. The pandemic has recharged that debate as clinical trials across the world test whether low doses of radiation can help treat covid-19 patients.

Katheryn Houghton (KHN)

But radon gas isn’t the same radiation U.S. doctors use, radiation experts caution. Radon is just one of the radioactive chemical elements and, because it’s a gas, it can be inhaled, making it particularly dangerous. Sitting in a radon-filled room and targeted radiation treatment in a medical facility are as different as “chalk and cheese,” said Brian Marples, a professor of radiation oncology at the University of Rochester.

“In clinical therapy, we know exactly what the dose is, we know exactly where it’s going,” he said.

Marples said much of the argument for radon’s therapeutic use relies on historical reports, unlike evidence-based research on clinical radiation. Still, some radiation experts are split on what level of radon should be deemed dangerous and whether it could have positive health effects.

Another concern: The radon treatment in the mines is largely unregulated. The Montana Department of Public Health and Human Services doesn’t have the authority to permit or license the mines, though department spokesperson Jon Ebelt said the adverse health risk from exposure is well known. The EPA also doesn’t have the power to mandate limits on radon.

‘Fountain of Youth’

Nonetheless, each year travelers head to western Montana, where four inactive mines flush with radon are within 11 miles of one another near the rural communities of Basin and Boulder. Day passes range from $7 to $15. The gas naturally forms when radioactive elements in the mountains’ bedrock decay.

Outside the Merry Widow Health Mine, a billboard-like banner announces “Fountain of Youth. FEEL YOUNG AGAIN!” Inside its tunnels, water seeps from the rock walls.

Those who want full immersion can slip into a clawfoot tub filled with radon-tainted water. People soak their feet and hands in water or simply sit and work on a puzzle. On a bench sits a printout of a Forbes article on clinical trials that show low-dose radiation could be a treatment for covid-19.

To owner Chang Kim, 69, his business is a mission, especially for those with chronic medical conditions such as arthritis or diabetes. Those who swear by radon therapy say that, in low doses, a little stress on the body triggers the immune system to readapt and reduces inflammation.

“The people coming to the mines, they’re not stupid,” Kim said. “People’s lives are made better by them.”

He learned about the mines 14 years ago when he and his wife, Veronica Kim, lived in Seattle and a connective tissue disease crumpled Veronica’s hands and feet. Traditional medicine wasn’t working. After two sessions a year in the mines ever since, Veronica smiles when she shows her hands.

Katheryn Houghton (KHN)

“They’re not deformed anymore,” she said, adding she’s been able to cut down on her use of meloxicam, a medication to reduce pain and swelling.

Tichenor said going to a mine with radon over six years has been one of the few things to calm his scleritis, a disorder that causes pain he describes as ice picks stabbing his eyes. As for its potential danger, he said radon treatment is just like any medication: Too much can cause harm. He and other radon users point to European countries such as Germany, where the therapy may be controversial but doctors still can prescribe radon treatments for various conditions that insurance may even cover.

(For another look inside the Merry Widow Health Mine, see this 2016 PNN story)

How Much Radiation Is Safe?

In the U.S., the EPA maintains that no level of radon exposure is risk-free even though everyone encounters the element in their lives. The agency notes radon is responsible for about 21,000 lung cancer deaths every year. It recommends that homeowners with radon levels of 4 picocuries per liter or more should add a radon-reduction system. By contrast, the owners of Montana’s oldest radon therapy mine, Free Enterprise Radon Health Mine, said their mine averages around 1,700.

Monique Mandali said the federal guidelines are “a bunch of baloney.” Mandali lives in Helena, about 40 minutes from the mines, and tries to fit in three sessions at Free Enterprise a year — 25 hours of exposure spread out over 10 days for arthritis in her back.

“People say, ‘Well, you know, but you could get lung cancer.’ And I respond, ‘I’m 74. Who cares at this point?’” she said. “I’d rather take my chances with radon in terms of living with arthritis than with other Western medication.”

Antone Brooks, formerly a U.S. Department of Energy scientist who studied low-dose radiation, is among those who believe the federal government’s no-level-of-radon-exposure stance goes too far. He pointed to research that indicates low doses of radiation potentially turn on pathways within bodies that could be protective. Though what’s considered a “low dose” depends on who’s talking.

“If you want to go into a radon mine twice a year, I’d say, OK, that’s not too much,” he said. “If you want to live down there, I’d say that’s too much.”

In the early 1900s, before antibiotics were popularized, small doses of radiation were used to treat pneumonia with reports it relieved respiratory symptoms. Since then, fear has largely kept the therapeutic potential of low-dose radiation untapped, said Dr. Mohammad Khan, an associate professor with the Winship Cancer Institute at Emory University. But amid the pandemic, health care providers struggling to find treatments as hospital patients lie dying have been giving clinical radiation another look.

So far, the trials Khan has led show that patients who received targeted low-dose radiation to their lungs got off oxygen and out of the hospital sooner than those without the treatment. Khan said more research is necessary, but it could eventually expand clinical radiation’s role for other illnesses.

“Some people think all radiation is the same thing, that all radiation is like the Hiroshima, Nagasaki bombs, but that’s clearly not the case,” Khan said. “If you put radiation in the hands of the experts and the right people — we use it wisely, we use it carefully — that balances risk and benefits.”

The logo for Free Enterprise Radon Health Mine is a miner skipping with crutches in the air. Roughly 70 years ago, a woman said her bursitis disappeared after visiting the mine several times. Thousands of others followed suit.

“We believe in it,” said Leah Lewis, who co-owns the mine with her husband, Ryan Lewis, and has relied on it to help treat her Crohn’s disease.

The couple live on-site and grew up in Boulder, going into the tunnels just as their 5-year-old daughter does now. Her husband’s great-grandfather owned the mine, and the business has been in the family ever since.

“Not one person has come back and said they’ve gotten lung cancer here,” Ryan Lewis said. “If they did, they would shut us down so fast.”

Aside from a billboard outside Helena, the family doesn’t really advertise the business. Clients tend to find them. Like many companies, Ryan Lewis said, Free Enterprise took a hit last year as people canceled plans because of the pandemic. Before that, he said, the business broke about even, adding that radon can be “a hard sell.”

But he said the family of cattle ranchers plans to keep it running as long as it doesn’t cost them money.

“The land is an investment, and we want to keep it in the family,” he said. “And there are a lot of people who use this, and there’s some responsibility there.”

Kaiser Health News is a national health policy news service. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

FDA Approves Spinal Cord Stimulator for Diabetic Neuropathy

By Pat Anson, PNN Editor

Like many other people with diabetic neuropathy, Lee Cagle suffered from burning and stinging sensations in his legs – pain so severe that he used sheets at night to build a small tent around his feet so that the fabric didn’t touch his skin and trigger another flare.

The 33-year-old Arkansas man tried pain medications such as hydrocodone and gabapentin (Neurontin), but didn’t like their side effects or potential for addiction.

“I don’t want to get hooked on pain meds. I’ve seen people hooked on pain meds and I didn’t want that for myself,” Cagle told PNN. “I only used them on the worst of worse days, when I could not fall asleep because I was in so much pain.”

Last year Cagle heard about a clinical trial for people with painful diabetic neuropathy (PDN) and decided to take a chance, enrolling in the study to see if a Nevro spinal cord stimulator could relieve his pain. The device emits mild electrical pulses to disrupt pain signals before they reach the brain. 

“It was almost instantaneous. The ease of the pain that it gave me,” Cagle said. “I felt so much better.”

The results from his two-week trial were so promising that Cagle agreed to have the stimulator permanently implanted along his spine during an outpatient procedure. That was nine months ago.

“I’m a completely different person now, compared to what I was before I got it put in my back,” said Cagle, who had only one minor setback when one of the electrodes leading from the stimulator failed.      

Cagle was one of 113 patients with PDN who had Nevro stimulators implanted during the clinical trial. Several dropped out of the study due to adverse events such as infections and two had their devices removed.

Most of those who remained reported significant pain relief of at least 50% and improved quality of life.

NEVRO IMAGE

The overall results were so promising that the Food and Drug Administration recently approved Nevro’s Senza stimulators for the treatment of PDN, making it the only spinal cord stimulation system approved for that condition. The Senza stimulators are unique because they use high frequency electric pulses of 10 kHz, a frequency that doesn’t create an uncomfortable tingling sensation that’s common with other stimulators.

"The substantial pain relief and improved quality of life demonstrates that 10 kHz Therapy can safely and effectively treat this patient population," said lead investigator Dr. Erika Petersen, Professor of Neurosurgery and Director of Functional and Restorative Neurosurgery at the University of Arkansas for Medical Sciences. "I'm grateful to my co-investigators and the patients who participated in this study, as the results and this approval will have far-reaching impact on the lives of PDN patients."

‘Dangerously Lax’ Oversight

FDA approval of the Nevro stimulator for PDN is a significant expansion of the medical device market. Of the 34 million Americans with diabetes, about one in five have painful neuropathy, a condition that develops when high blood glucose levels damage peripheral nerves. Until now, most spinal cord stimulators were only approved for patients with severe back pain.

FDA approval also comes at a time when the agency is under growing scrutiny for its regulation of medical devices, particularly spinal cord stimulators. A 2020 report by Public Citizen accused the FDA of “dangerously lax” oversight of stimulators, which were linked to 156,000 injuries and 931 deaths. Ironically, the report noted that spinal cord stimulators are often touted as safer alternatives to opioid medication.  

“In the midst of the opioid crisis, medical device companies and medical centers that implant spinal cord stimulators increasingly have been marketing spinal cord stimulation as an alternative to opioids for chronic pain,” the report found. “Importantly, no evidence was provided that spinal cord stimulators reduce the use of opioids.”  

The FDA responded to the Public Citizen report by sending a letter to healthcare providers reminding physicians to only implant stimulators after a trial period that demonstrates the device provides effective pain relief. An FDA review of adverse events involving spinal cord stimulators found that nearly a third were reports of unsatisfactory pain relief. Even worse, the review identified nearly 500 deaths linked to the devices between 2016 and 2020.

A new study published this week in JAMA Internal Medicine concluded that the FDA’s adverse events reporting system for medical devices may significantly underestimate the number of deaths that actually occur. Researchers found the system relies too heavily on adverse events reported by device manufacturers.

The Center for Medicare Services (CMS) is also taking a harder look at spinal cord stimulators. On July 1, CMS implemented a new rule requiring Medicare patients to get prior authorization before a stimulator is implanted. The agency said there has been significant expansion in the use of spinal cord stimulators – about 50,000 are now implanted every year in the U.S. – but it could find no medical reason to justify the increasing number of procedures.

“After reviewing all available data, we found no evidence suggesting other plausible reasons for the increases, which we believe means financial motivation is the most likely cause," CMS said.

Industry groups and some members of Congress lobbied hard against the CMS rule, saying prior authorization would create “significant barriers to access to medically necessary procedures.”    

For patients who are desperate for pain relief, who find medication ineffective or difficult to obtain, spinal cord stimulation may be one of the few options remaining. Asked if he would recommend the Nevro stimulator to other DPN patients, Lee Cagle said he would.

“Definitely. Most definitely. I’m a totally different person now,” he said. “If Nevro came in with something else, if they needed me for a trial study, I wouldn’t hesitate.”  

Can Psychedelics Be Used to Treat Fibromyalgia?

By Pat Anson, PNN Editor

A startup pharmaceutical company has announced plans for a clinical trial to see if a psychedelic compound may be useful in treating fibromyalgia.

California-based Tryp Therapeutics is partnering with scientists at the Chronic Pain & Fatigue Research Center at University of Michigan Medical School for the Phase 2a study, which would be the first to evaluate the effictiveness of psilocybin – the psychoactive compound in “magic mushrooms” -- in treating fibromyalgia.

"We are thrilled to collaborate with such forward-looking clinicians and scientists to develop additional treatment options for fibromyalgia," Jim Gilligan, PhD, Tryp’s President and Chief Science Officer said in a statement.

"The Chronic Pain & Fatigue Research Center at the University of Michigan brings incomparable experience with evaluating treatments for fibromyalgia and other chronic pain indications, and there is nothing more important to our collective team than creating therapies that will address the daily distress of these patients."

The study will evaluate the safety and efficacy of TRYP-8802, an oral formulation of synthetic psilocybin developed by Tryp. The treatment, which will also include psychotherapy, is designed to target pain through neuroplasticity, which alters and reorganizes neural networks in the brain.

Fibromyalgia is a poorly understood disorder characterized by widespread body pain, fatigue, poor sleep, anxiety and depression. Standard treatments for fibromyalgia, such as non-steroidal anti-inflammatory drugs (NSAIDs) and gabapentinoids (Lyrica, Neurontin), often prove to be ineffective or have unwelcome side effects.

"Existing treatment options for fibromyalgia are often ineffective and show significant side effects," said Daniel Clauw, MD, Director of the Chronic Pain & Fatigue Research Center.

Tryp plans to submit an Investigational New Drug application to the FDA for the Phase 2 trial in September. Phase 2 studies typically involve a few hundred people with a disease or condition, and are designed to test the safety and efficacy of a treatment.  A much larger Phase 3 study is usually required before the FDA will even consider approval.

Interest in using psychedelics to treat medical conditions has been growing in recent years, primarily as a way to treat depression, anxiety and other mental health issues. Preliminary research suggests that microdoses of LSD, psilocybin and other psychedelics may also be effective in treating pain.

Another pharmaceutical startup – Mind Medicine (MindMed) – recently announced plans to  investigate LSD as a treatment for cluster headache and an unnamed “common, often debilitating, chronic pain syndrome.”

Tryp Therapeutics is focused on developing psilocybin-based compounds for the treatment of diseases with unmet medical needs. The company recently announced a partnership with the University of Michigan to study synthetic psilocybin as a treatment for neuropsychiatric disorders. Tryp is also working with the University of Florida to investigate psilocybin as a treatment for eating disorders.

LSD, psilocybin and other psychedelics are classified as Schedule I controlled substances, meaning they have a high potential for abuse and currently have no accepted medical use in the United States.

A New Option for Young Migraine Sufferers

By Pat Anson, PNN Editor

Migraines can have a devastating impact on children and adolescents. In addition to causing head pain, upset stomachs and visual disturbances, migraine attacks can disrupt school and social activities at a sensitive time in a young person’s life.

Although pediatric migraines are common, affecting about 10% of school-age children and one in five teenagers, treatment options are very limited compared to adults. There are no FDA approved pharmaceutical migraine treatments for kids under the age of 12. That leaves doctors to prescribe migraine medication to children off-label, including a new class of migraine drugs called CGRP inhibitors, which have not yet been approved or studied in young children. 

A small new study suggests there may be a safer and more effective option for young migraineurs: neuromodulation. Research recently published in the journal of Pain Medicine found that Nerivio, a neuromodulation device worn on the upper arm, was more effective in treating acute migraine in adolescents than triptans and over-the-counter pain relievers. Nerivio uses smartphone-controlled electrical pulses to stimulate nerves and disrupt pain signals.

“To my knowledge, this is the first study that directly compared remote electrical neuromodulation and standard-care treatment options in adolescents,” says lead author Andrew Hershey, MD, co-director of the Headache Center at Cincinnati Children’s Hospital Medical Center.

“Migraine in adolescents is associated with poorer performance and absence from school and social activities during a particularly formative time in life. Providing teens with more effective and engaging treatments for migraine can have far-reaching positive effects over the course of their lives.”

Nerivio was developed by Theranica, an Israeli medical technology company that sponsored the study. The FDA approved the device as a treatment for acute migraine in adults in 2019 and recently expanded the label to include children over the age of 12 with episodic or chronic migraine.

THERANICA IMAGE

Thirty-five adolescent migraine patients aged 12 to 17 took part in the two-month comparison study. Over-the-counter drugs and oral triptans were used by patients during the medication month, and Nerivio during the Remote Electrical Neuromodulation (REN) month.

Two hours after treatment, over a third (37%) of patients achieved complete pain freedom during the REN phase of the study, compared to just 8.6% in the medication phase. Some degree of pain relief was reported by 80% of patients in the REN phase, as opposed to 57% in the medication phase.

“This study provides evidence that Nerivio may be considered as a first-line acute treatment, especially for adolescents with medication restricting comorbidities or a preference for a non-medication-based treatment,” said co-author Samantha Irwin, MD, a pediatric neurologist at the UCSF Benioff Children Hospital in San Francisco. “The importance of having a non-pharmacologic, discrete, easy-to-use and effective acute treatment in the adolescent armamentarium cannot be overstated.”

Long-Term Effects of Childhood Migraine

Early treatment of childhood migraine is important because there is emerging evidence that repeated headache attacks in children reduce the formation of “gray matter” in parts of the brain that process pain signals, leading to more frequent and severe migraines in adults.   

“We’ve done studies here independent of any pharmaceutical company where we’ve show that the earlier we can intervene with effective therapy and education of patients, the better their long-term outcome,” Hershey told PNN. “So we really have this opportunity to intervene with a child or adolescent that can affect them for their life.

“A device can be as effective as a drug. What I tell patients is that it gives them their own locus of control. Instead of taking a medication and hoping it works, they’re actually controlling the device with their smartphone, and so they can really take control of their headaches, which is ultimately what we want them to do.”    

Nerivio is only available by prescription and is eligible for insurance. When purchased wholesale, the listed price is $599 for a twelve-treatment unit, although buyers can save money by enrolling in a patient savings program, depending on their insurance coverage.  

Theranica is currently recruiting patients for a placebo-controlled study to see if Nerivio may be effective in preventing migraines. The company is also investigating whether the device may help treat other chronic pain conditions besides migraine.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

The ‘Crazy’ Healing Power of Music

By Cynthia Toussaint, PNN Columnist

As a young person, I don’t remember a time when I didn’t live and breathe music.

In grade school, I couldn’t wait to get to the multi-purpose room for two reasons: chorus to sing my heart out and band to play my beloved flute. I pestered my mother relentlessly to let me start piano lessons before age seven (a family rule) because I loved the way it sounded and couldn’t wait to make the notes on the page come to life.

Then there was my favorite. When Mom brought home the record “Funny Girl”, I knew that I’d never stop singing. It was pure joy, an extension of myself. Indeed, the best part of Christmas each year was receiving a new Barbra Streisand album, a treasure that I cherished to the point of wearing out the grooves.

I grew to be a nonstop, never-gonna-quit singer, dancer and actor. It’s what I lived for, what I was born to do. Nothing was going to stop me – and in the end, nothing really did. While we don’t get to live our dreams with Complex Regional Pain Syndrome, we can hold onto our passions in a different way. And for wellness alone, we ought to.

People gasp when they hear that I was unable to speak for five years due to CRPS, because that’s an unthinkable symptom caused by an unimaginable disease. But those same people overlook the fact that CRPS made me unable to sing for 15 years, like that was something disposable.

When I couldn’t sing, I didn’t get to be Cynthia. Something fundamental and basic was stripped away from me. And with that went my expression and joy.

Lately I’m hearing lots about the healing powers of expressive therapy and how creative pursuits like dancing, painting, writing and acting can unleash “feel-good” hormones (like endorphins and oxytocin) that lessen pain, depression and anxiety. I’ve also come to understand that the part of the brain that drives creativity distracts from the part that controls pain. That’s certainly been the case with me.

Cooler still, partaking in one expressive therapy can lead to the recovery of another. It was soon after writing my memoir that I could feel my body getting ready to sing again. Regaining my voice was nothing short of a miracle and, to this day, I don’t really understand how it happened. My best guess is that through the narrative therapy process I purged negative feelings and wounds, opening a healing space. But in the end, does it matter?

Now that I’ve regained my strong vocal chords, I take every opportunity to express this joy. I sing with bands, in choirs, duets with musicians and a cappella harmony trios. I also love to record – and just finished my second CD titled Crazy, which I dedicated to “women in pain who know they’re not.” 

This album was a real labor of love as I took my time (in fact, seven years!) to record it. The obstacles throughout were many – multiple CRPS flares, a broken elbow that went untreated and undiagnosed for a year, a lupus infusion drug that nearly did me in, and, oh yeah, breast cancer.

For this album, I delighted in choosing songs that took me down memory lane, songs that I loved while growing up and that speak differently to me post-illness. I had to quickly wrap up my last two recordings in December 2019 as the dark chemo clouds loomed.

Then, after becoming an unlikely cancer survivor, I eagerly designed my cover. I hadn’t been on a beach for 35 years and was bald, but that didn’t stop me from being a mermaid, leaning against my fears while having them bolster me to look toward a bright future. 

I want Crazy to bring joy and laughter to those who suffer. I’m hoping this near-and-dear project will inspire us to turn our backs on fear and “impossibles,” reignite our passions and courageously move on.

I still hear from women in pain who are stuck in the elusive search for a cure in hopes of recapturing their past. Here’s the thing – we don’t get to go back.

Our choice is to stay stuck and miserable – or let the “cure” delusion go and partake in things that bring us healing and wholeness. I’m certain that one of the tickets forward is expressive therapy. When we stir our soulful passions, wellness follows.

As a former “triple threat” performer, it’s the expressive arts that continue to inspire me to heal. For you it might be a way different sort of passion. Perhaps nature, animal welfare or the pursuit of justice is your buzz. Bottom line, we all need to find ways to differently recapture what clicks our heels and makes the hair on the back of our necks stand straight. 

Being a long-time member of the Kingdom of the Sick doesn’t exclude us from the pursuit of joy. I know it’s easier said than done when wrangling with the likes of CRPS, migraine or lupus. But it’s essential to living a full, authentic life, one worth seeing the glow of a spectacular sunset.            

I don’t think there’s anything crazy about that.                     

Cynthia Toussaint is the founder and spokesperson at For Grace, a non-profit dedicated to bettering the lives of women in pain. She has lived with Complex Regional Pain Syndrome (CRPS) and 19 co-morbidities for nearly four decades, and became a cancer survivor in 2020. Cynthia is the author of “Battle for Grace: A Memoir of Pain, Redemption and Impossible Love.”

Click here to download or order her Crazy CD.

Diet Changes Reduce Migraine Headaches

By Pat Anson, PNN Editor

There are many new treatments available for migraine sufferers; everything from CGRP inhibitors to neuromodulation to green light therapy. But there may be a simpler and less expensive way to reduce the frequency and severity of migraine headaches: changing your diet.

A new study funded by the National Institutes of Health found that migraine sufferers who ate more fatty fish and reduced their consumption of polyunsaturated vegetable oils had fewer headaches.

The findings are similar to another recent study that found foods containing healthy omega-3 fats – such as fish, flaxseed and walnuts – can reduce inflammation and neuropathic pain. Researchers say the two studies suggest that dietary changes can affect pain levels for other types of chronic pain.  

“It may ultimately be possible to integrate targeted dietary changes alongside medications to improve the lives of patients with chronic pain,” said Chris Ramsden, MD, a clinical investigator and adjunct faculty member at the University of North Carolina at Chapel Hill.

“Biochemical findings from both studies support the biological plausibility for this type of approach and could open the door to new approaches for managing many types of chronic pain. What is needed now is more evidence from randomized controlled trials in other populations with chronic pain.”

Ramsden is lead author of a study, published in the British Medical Journal, in which 182 adults with frequent migraines were broken into three groups and put on special diets for 16 weeks.

One group received meals that had high levels of fatty fish and low amounts of linoleic acid, a polyunsaturated fatty acid commonly found in American diets of corn, soybean and other vegetable oils. A second group received meals that had high levels of fatty fish and higher linoleic acid. The third control group received meals with high linoleic acid and low levels of fatty fish to mimic what an average American consumes.

"Our ancestors ate very different amounts and types of fats compared to our modern diets," said co-first author Daisy Zamora, PhD, an assistant psychiatry professor in the UNC School of Medicine. "Polyunsaturated fatty acids, which our bodies do not produce, have increased substantially in our diet due to the addition of oils such as corn, soybean and cottonseed to many processed foods like chips, crackers and granola."

When the study began, participants averaged over 16 headache days per month and over five hours of migraine pain each headache day -- despite taking multiple headache medications.

Those who consumed a diet low in vegetable oil and high in fatty fish had 30% to 40% reductions in total headache hours per day, severe headache hours per day, and overall headache days per month compared to the control group.

Blood samples from this group also had lower levels of pain-related omega-6 fatty acids found in processed foods.

“The effect we saw for the reduction of headaches is similar to what we see with some medications.”

— Daisy Zamora, PhD, UNC School of Medicine

“Our trial is the first moderate sized controlled trial showing that targeted changes in diet can decrease physical pain in humans,” Ramsden told PNN, noting that fatty acids appear to regulate the production of calcitonin gene-related peptides, the same protein targeted by CGRP medications.

“Diets alter the amounts of omega-3 and omega-6 fatty acids in the nervous system and other tissues linked to chronic pain. These fatty acids are converted by the body into biochemical mediators of pain. Several of these biochemical mediators act on receptor channels to regulate CGRP release,” he said in an email.

"I think this modification in diet could be impactful," Zamora added. "The effect we saw for the reduction of headaches is similar to what we see with some medications.”

Zamora, Ramsden and their colleagues are currently working on a new study to test diet modification for other chronic pain syndromes.

Can a Low-Fat Diet Reverse Neuropathic Pain?

By Pat Anson, PNN Editor

Low fat diets are often recommended for people suffering from obesity and cardiovascular disease, but changes in eating habits are rarely recommended for people who live with chronic pain.

That could be changing thanks to a new study by researchers at the University of Texas Health Science Center, who found that diets high in omega-6 fats are strongly associated with inflammation and neuropathic pain. Omega-6 fats are widely found in typical Western diets of fast food, processed snacks, cakes, and fatty or cured meats.

Conversely, researchers say foods containing healthy omega-3 fatty acids – such as fish, flaxseed and walnuts – could reduce or even reverse neuropathic pain associated with diabetes. Their findings were recently published in the journal Nature Metabolism.

Diabetic neuropathy is a progressive and painful disease that causes burning or stinging sensations in the hands and feet. Many drugs used to treat neuropathic pain, such as gabapentin and pregabalin, often don’t work or have unpleasant side effects.

“This paper is a high-profile contribution for a huge unmet translational need as there are no treatments altering the nature of this neurological disease,” said José Cavazos, MD, director of the South Texas Medical Scientist Training Program at UT Health San Antonio.

In experiments on humans and laboratory animals, UT researchers found that mice fed a diet high in omega-6 polyunsaturated fats became hypersensitive to pain, cold and heat stimulation – signs of peripheral nerve damage. Lowering the amount of omega-6 fats and increasing omega-3 fatty acids reduced pain sensitivity in the mice.

The researchers also found that high levels of omega-6 lipids in the skin of patients with Type 2 diabetes were strongly associated with neuropathic pain and the need for analgesic drugs.

“We believe that these data warrant continued investigation of peripheral fatty acid and metabolite levels as potential pain biomarkers. Such biomarkers could provide clinicians with reliable objective endpoints to guide diagnoses as well as decision making on treatment regimens, including therapeutic diets,” wrote lead author Jacob Boyd, MD, UT Health San Antonio.

About 34 million people in the U.S. have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.

A 2015 study found that a vegetarian diet coupled with vitamin B12 supplements significantly reduced pain and improved the quality of life of people with diabetic neuropathy. Participants also had lower blood pressure and cholesterol levels, and lost an average of 14 pounds.

Tiny Electrode Could Expand Use of Spinal Cord Stimulators

By Pat Anson, PNN Editor

A tiny inflatable device – about the width of a human hair – could make spinal cord stimulation less invasive and more practical for millions of people who suffer from chronic back or leg pain, according to researchers at the University of Cambridge.

Long considered the treatment of last resort, spinal cord stimulators (SCSs) are bulky devices implanted along the spine that use electrode wires connected to a battery to emit electric currents that block pain signals from reaching the brain. About 50,000 stimulators are surgically implanted every year, but many wind up being removed due to complications from surgery or because they are ineffective.

“Our goal was to make something that’s the best of both worlds – a device that’s clinically effective but that doesn’t require complex and risky surgery,” said Christopher Proctor, PhD, a research fellow at Cambridge’s Department of Engineering and one of the senior authors of a study published in Science Advances. “This could help bring this life-changing treatment option to many more people.”

Proctor and his colleagues developed a miniaturized electrode that is so small it can be rolled up into a tiny cylinder, inserted into a needle, and implanted into the epidural space of the spinal column.

As the video below shows, the device can then be inflated with water or air so that it unrolls like a tiny air mattress and covers part of the spine. When connected to a battery, the ultra-thin electrode can send small electric currents to the spinal cord, just like a traditional stimulator.

“In order to end up with something that can be implanted with a needle, we needed to make the device as thin as possible,” said co-author Ben Woodington, a PhD candidate in Cambridge’s Department of Engineering.

Researchers made the device with flexible electronics used in the semiconductor industry; tiny fluidic channels used in drug delivery; and shape-changing materials used in robotics.

“Thin-film electronics aren’t new, but incorporating fluid chambers is what makes our device unique – this allows it to be inflated into a paddle-type shape once it is inside the patient,” said Proctor.  

Early versions of the device were so thin they were invisible to x-rays, which surgeons would need to confirm the device was in the right place before inflating it. Researchers added some bismuth particles to make the device visible without increasing the thickness too much.

The experimental device has only been tested in human cadavers. More extensive testing and clinical trials will be required before the device can be used on patients – possibly in two or three years. The Cambridge research team is currently working with a manufacturer to further develop and improve the device.

“The way we make the device means that we can also incorporate additional components – we could add more electrodes or make it bigger in order to cover larger areas of the spine with increased accuracy,” said senior co-author Damiano Barone, MD, a clinical lecturer in Cambridge’s Department of Clinical Neurosciences.

“This adaptability could make our SCS device a potential treatment for paralysis following spinal cord injury or stroke or movement disorders such as Parkinson’s disease. An effective device that doesn’t require invasive surgery could bring relief to so many people.”

“This technology has the potential to transform clinical treatment, significantly improve pain management for so many people, and reach patients who cannot be treated with existing devices,” said Rachel Atfield, PhD, Commercialisation Manager at Cambridge Enterprise, which has patented the device.

A 2018 study by a team of investigative journalists found that spinal cord stimulators have some of the worst safety records of medical devices tracked by the U.S. Food and Drug Administration. A review of FDA data found over 500 deaths and 80,000 injuries involving stimulators since 2008. Patients reported being shocked or burned by the devices and many had them removed.