Can ‘Medical Food’ Treat Chronic Pain?

By Pat Anson, PNN Editor

Do you keep a supply of gamma-aminobutyric acid in your medicine cabinet? What about hydroxytryptophan? Or the ominous sounding devil’s claw root?

They’re not exactly household names to the average person, but to Fabio Lanzieri they are essential ingredients in a new “medical food” product called Proleeva, a dietary supplement he developed that contains a blend of a dozen natural herbs, enzymes and amino acids.

“I fervently believe that prescription medications are very beneficial to man, but I also believe that nature does offer us the ability to find solutions to natural diseases. Because of this, I was always interested and read a lot about vitamins, supplements and bioflavonoids,” says Lanzieri, who spent nearly four decades in the pharmaceutical industry. “I believe that supplementing prescription medications with natural substances is the best way of treating chronic pain or any disease state.”

Several years ago, Lanzieri’s wife Maria began experiencing joint pain as a side effect of taking a hormone suppressant to help her recover from breast cancer.     

“I did start feeling the pain in my joints, particularly my fingers. I was having a really hard time sometimes just opening a bottle or doing simple things,” Maria told PNN.

To help his wife, Lanzieri began experimenting with different blends of herbs and other natural substances. Some, like ginseng and curcumin, have been used for centuries as natural remedies for pain and inflammation. Others, like choline bitartrate and L-arginine, have only recently been recognized as essential nutrients that help restore amino acids and neurotransmitters to healthy levels.

You can buy all of these supplements individually, but Lanzieri combined them all into one proprietary formula and gave it to Maria. Her joint pain slowly began to improve.

“After about a month, month and a half, I started having relief of those symptoms.  I didn’t have the joint pain. I felt like I could do a lot of those tasks that I couldn’t do before,” Maria said. “At one point I stopped taking it and it then was all coming back. It was weird. I didn’t think it was the Proleeva. I didn’t associate it with that. But then I went back on it and suddenly I was not feeling it again.”

The Lanzieri’s began sharing Proleeva with family and friends, who also reported positive results.

Only recently have they begun selling Proleeva to the general public on their website and through Amazon, marketing it as “the ultimate comfort food” that “helps bring your nervous system back into balance.”

A Proleeva bottle contains 120 capsules – about a month’s supply – and costs $40.

“I’ve been taking Proleeva for the last seven years and I don’t have any inflammation. I take it because it balances the body with the right ingredients that it needs to fight to heal itself,” says Lanzieri. “Your body needs amino acids and they are not reproduced naturally in the body. And over time, the older we get, the less we have of those amino acids. And therefore, we have to supplement them.”

For now, there is only anecdotal evidence to support these health claims, although a small clinical trial of Proleeva is underway.  Unlike pharmaceuticals, dietary supplements are only loosely regulated by the Food and Drug Administration, allowing supplement makers to introduce new products and make health claims without substantial evidence that they work.

‘One Formulation Makes a Lot of Sense’

Dr. Forest Tennant is intrigued by Proleeva. An expert in treating intractable pain, Tennant recommends that pain patients take gamma-aminobutyric acid (GABA), herbs and other supplements as part of their medical treatment to restore damaged nerve tissue and relieve pain.

“Having a lot of different supplements in one formulation actually makes a lot of sense, because we’re not certain which ones are going to work,” says Tennant. “But I do think there is some urgency or necessity in people with pain taking a variety of these supplements. They can’t hurt themselves and they probably are going to benefit themselves.

“And this particular product is doing something else. It recognizes that it’s got stuff in there like GABA that stimulates the nerve receptors that provide pain relief.”  

Tennant says the supplement industry has become more innovative than the pharmaceutical industry – particularly in an age when opioids and some other medications are harder to get.

“I think the innovation is really great,” Tennant said. “I really think that anyone who has chronic pain, particularly constant pain, really needs to be on a number of supplements right now. We’ll figure out exactly which ones work the best later, but right now I think taking a combination of these things is worthwhile.”

People who try Proleeva or other supplements should not expect instant results. It may take up to a month to feel any benefits.

“The biggest problem is making them stay with this for 30 days. We’re a society of instant gratification. Prescription drugs do that. But unfortunately, natural substances take time,” says Lanzieri.

Lipofilling Improved Pain and Function in Patients with Finger Osteoarthritis

By Pat Anson, PNN Editor

People who suffer from painful arthritic fingers have few treatment options to choose from. They can wrap their hand in a splint, take anti-inflammatory drugs or get steroid injections into their finger joints – all of which provide only temporary relief. More invasive surgical treatments include joint fusions or reconstruction, which can impair hand motion and take weeks to recover from.

German researchers have found that a less invasive treatment commonly used in plastic surgery – injecting fat tissue from one part of the body into another -- can provide lasting improvements in pain and function for patients with finger osteoarthritis. The technique – called lipofilling – resulted in “highly significant clear improvement" with no complications in a small pilot study of 15 patients.     

"We believe that for our patients the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect," said co-author Max Meyer-Marcotty, MD, Clinic for Plastic, Reconstructive, and Aesthetic Surgery/Hand Surgery in Lüdenscheid, Germany.

"Even over a long-term follow-up, the transfer of fatty tissue to arthritic fingers joints appears to provide a safe and minimally invasive alternative to conventional surgery for patients with osteoarthritis.”

In the lipofilling procedure, Meyer-Marcotty and his colleagues used liposuction to take a small sample of each patient's fatty tissue from their upper thigh or hip area. The autologous fat was then injected into their arthritic finger joints. Patients wore a splint around the treated fingers and took pain relievers for a week. There were no infections or other complications reported.

The researchers followed outcomes in 25 finger joints for an average of 44 months after treatment, and found that pain scores fell from a median of 6 (on a 10-point scale) before treatment to just 0.5 points at follow-up. Grip strength of the treated fingers approximately doubled, while fist closure and hand function performing everyday tasks also improved.

“Even after a follow-up examination period of 44 months, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe, and promising alternative to conventional surgical techniques aimed at alleviating arthritic complaints, and one that among other things entails a highly significant improvement in postsurgical pain levels,” researchers reported in the journal Plastic and Reconstructive Surgery. “Further long-term follow-up studies of even larger patient cohorts would be needed to further corroborate these initial positive findings.”

In recent years, lipofilling procedures have been increasingly used in plastic and reconstructive surgery, as well as stem cell therapy.

When injected into patients, mesenchymal stromal cells (MSCs) in fat tissue can regenerate damaged or diseased tissue, including cartilage in arthritic joints. A small 2019 study found that MSCs collected from a patient’s bone marrow can significantly reduce pain from knee osteoarthritis for up to a year.

Osteoarthritis is a progressive joint disorder caused by the inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

"The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis," said Meyer-Marcotty. "Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed."

High-Frequency Spinal Cord Stimulators Provide More Pain Relief

By Pat Anson, PNN Editor

Spinal cord stimulators are often considered the treatment of last resort for patients with intractable or severe chronic pain. The surgically implanted devices emit low levels of electricity that reduce pain signals, but have high failure rates and often have to be removed because they’re ineffective, cause infections or need new batteries.

Two new studies suggest there are ways to improve the success rate of spinal cord stimulators (SCS) through improved patient selection and the use of high-frequency devices.

Low-frequency SCS (50 Hz) was first approved by the Food and Drug Administration for intractable back and leg pain in 1989. Six years later, the FDA approved high-frequency devices (10,000 Hz), that deliver pulses of electrical stimulation that are shorter in duration, lower in amplitude and do not cause paresthesia, an irritating sensation of tingling or prickling.

In a retrospective study of 237 patients who received stimulators between 2004 and 2020, researchers at the University of California San Diego School of Medicine reported that high-frequency devices were more effective at reducing pain and opioid use than low-frequency ones.

The study findings, published in the journal Bioelectronic Medicine, also show that male patients benefit more than women from high-frequency neuromodulation.

"Our work was sparked by a growing literature that demonstrate sex specific immune pathways differentially contribute to chronic pain processes," said senior author Imanuel Lerman, MD, an associate professor of anesthesiology at UC San Diego Health. "The observed parameter-specific (high versus low frequency) sex-based differences in spinal cord stimulation efficacy and opiate use are definitely intriguing.”

It’s not clear why men benefit more than women, but researchers believe it may be due to the male hormone testosterone having a modulating effect on pain signals. The sex differences may also be due to males and females processing chronic pain differently.

"Clearly more work needs to be done to carefully characterize sex specific pain regulatory pathways that may prove responsive to specific types of neuromodulation and or pharmaceutical therapies," said Lerman.

Improved Patient Selection  

Although most patients are required to undergo psychological testing and a trial treatment before getting a SCS, failure rates for the devices remain high at around 25 to 30 percent. With about 50,000 stimulators implanted in the U.S. every year, that means thousands of patients are getting poor results.

To improve patient outcomes, researchers at Florida Atlantic University developed machine-learning algorithms to help predict which patients may benefit from SCS. Working with a cohort of 151 SCS patients, they evaluated 31 features or characteristics in each patient.  

Researchers found two distinct clusters of patients which differ significantly in age, duration of chronic pain, preoperative pain levels and pain catastrophizing scores. They used computers to fine-tune the results, identifying the 10 most influential features that contribute the most to a successful SCS implant.

Results of the study, published in the journal Neurosurgery, demonstrate for the first time the ability of machine-learning algorithms to predict long-term patient response to SCS placement. The next step is to validate the data in future patients to ensure that the algorithm is useful in real-world situations, not just computer models.

"Our study resulted in the development of a model to predict which patients would benefit from spinal cord stimulation," said lead author Julie Pilitsis, MD, dean and vice president of medical affairs at Florida Atlantic University's Schmidt College of Medicine.  "After we validate this work, our hope is that this machine-learning model can inform a clinical decision support tool to help physicians better choose which patients may be most appropriate."

SCS is no longer limited to patients with intractable back and neck pain. Last year the FDA expanded the use of SCS to include lower limb pain from diabetic neuropathy.  Stimulators are also being used on patients with Complex Regional Pain Syndrome (CRPS).

A decision to get a SCS shouldn’t be taken lightly. A 2018 study by a team of investigative journalists found that stimulators have some of the worst safety records of medical devices tracked by the FDA. A 2020 FDA review of adverse events involving SCS found that nearly a third were reports of unsatisfactory pain relief. The review also identified nearly 500 deaths linked to the devices, along with nearly 78,000 injuries and 30,000 device malfunctions.

Low Fat Vegan Diet Reduces Rheumatoid Arthritis Pain

By Pat Anson, PNN Editor

A small new study found that a low-fat vegan diet can help improve joint pain in patients with rheumatoid arthritis – the latest research to show that healthier diets can significantly reduce pain levels. Study participants also lost weight and lowered their cholesterol levels by eliminating their consumption of animal fats and inflammatory foods.

Rheumatoid arthritis (RA) is a progressive and incurable disease in which the body’s immune system attacks joint tissues, causing pain, inflammation and bone erosion.

“A plant-based diet could be the prescription to alleviate joint pain for millions of people suffering from rheumatoid arthritis,” says lead author Neal Barnard, MD, president of the Committee for Responsible Medicine. “And all of the side effects, including weight loss and lower cholesterol, are only beneficial.”

Thirty-two people diagnosed with RA from the Washington DC area completed the study after being assigned to one of two groups for 16 weeks.

The first group followed a vegan diet for four weeks, eliminating their consumption of meat, dairy products and eggs. During weeks 5 through 7, the diet was further restricted to eliminate gluten-containing grains, as well as potatoes, chocolate, nuts, citrus, onions, tomatoes, bananas, apples and coffee.

Vegan foods that participants were encouraged to eat included rice, oats, quinoa, broccoli, kale, collards, Brussels sprouts, squash,  carrots, apricots, blueberries, plums, lentils and beans. There were no restrictions on calories or how often they ate.

After week 7, the excluded foods were reintroduced, one at a time, every 2 days. Any food that was associated with pain or other symptoms upon reintroduction was eliminated

The second group followed an unrestricted diet but were asked to take a daily placebo capsule.  After 16 weeks, the groups switched diets.

The study findings, published in the American Journal of Lifestyle Medicine, showed a significant reduction in pain and inflammation during the vegan stage of the study. Participants lost an average of two points in their Disease Activity Score-28 (DAS28), which measures swollen joints, joint tenderness and C-reactive protein levels – a marker for inflammation. DAS28 levels typically increase with rheumatoid arthritis severity.

The average number of swollen joints decreased from 7.0 to 3.3 in the vegan phase, while increasing slightly for participants in the placebo phase.

In addition to reductions in pain and swelling, participants lost an average of 14 pounds on the vegan diet, compared with a gain of about 2 pounds on the placebo diet. There were also greater reductions in total, LDL, and HDL cholesterol during the vegan phase.

Notably, although participants were asked not to alter or reduce their use of medication during the study, several of them did so – in most cases because they felt less need for them.

“In conclusion, the current study suggests that a low-fat vegan diet eliminating specific foods, without fasting and without caloric restriction, may improve joint pain. Additional studies are needed in which the diagnosis is confirmed by independent observers and medications remain stable in a larger sample,” said Barnard.

Many previous studies have shown an association between healthy diets and lower pain levels. Gluten-free diets have been shown to improve symptoms of fibromyalgia and neuropathy, while Mediterranean diets rich in anti-inflammatory foods lower the risk developing chronic pain. And diets that include lots of fatty fish and less processed food reduce the frequency and severity of migraines.

One of the strictest diets of all – a very low energy diet (VLED) that limits people to just 800 calories a day – was recently found to significantly reduce fibromyalgia pain after just three weeks.

Tiny Experimental Implant Could Treat Neuropathic Pain

By Pat Anson, PNN Editor

A tiny wireless implant that stimulates peripheral nerves from within blood vessels shows potential as a treatment for neuropathic pain, according to a proof-of-concept study by a team of Texas researchers published in the journal Nature Biomedical Engineering.

The implants have only been tested in laboratory animals, but researchers say they could replace larger and more invasive devices currently used to treat Parkinson’s disease, epilepsy, chronic pain, hearing loss and paralysis.

The MagnetoElectric Bio ImplanT -- ME-BIT for short -- is slightly larger than a grain of rice. It’s designed to be placed in a blood vessel near the nerve targeted for stimulation. The implant requires no surgery or batteries, and draws its power and programming from an electromagnetic transmitter worn outside the body.

“Because the devices are so small, we can use blood vessels as a highway system to reach targets that are difficult to get to with traditional surgery,” said lead author Jacob Robinson, PhD, Associate Professor of Electrical and Computer Engineering at Rice University.

RICE UNIVERSITY

“We’re delivering them using the same catheters you would use for an endovascular procedure, but we would leave the device outside the vessel and place a guidewire into the bloodstream as the stimulating electrode, which could be held in place with a stent.”

The ability to power the implant remotely eliminates the need for electrical leads through the skin and other tissues. Leads used for devices like pacemakers can cause inflammation and sometimes need to be replaced. Battery-powered implants may also require additional surgery to replace the batteries.

Researchers say ME-BIT’s wearable charger could even be misaligned by several inches and still provide sufficient power and programming to the implant, without irritating surrounding tissues.

“We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders – depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection,” said co-author Sunil Sheth, MD, Associate Professor of Neurology and director of the Vascular Neurology Program for McGovern Medical School at UTHealth Houston.

“If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Electrical stimulation can reduce pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. But existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

By using blood vessels, researchers say they can place the ME-BIT implant strategically in a minimally invasive way and have more predictable outcomes.

“One of the nice things is that all the nerves in our bodies require oxygen and nutrients, so that means there’s a blood vessel within a few hundred microns of all the nerves,” Robinson explained. “With a combination of imaging and anatomy, we can be pretty confident about where we place the electrodes.

In a previous study, Robinson and his colleagues demonstrated the viability of the implants by placing them beneath the skin of laboratory rodents that were fully awake and free to roam about their enclosures. The rodents preferred to be in parts of the enclosures where a magnetic field activated the implant, which provided a small voltage to the reward center of their brains.

Researchers need to conduct more animal studies and eventually human trials before seeking FDA approval for the implants.

“We’re doing some longer-term studies to ensure this approach is safe and that the device can stay in the body for a long time without causing problems,” said Sheth, who estimates the process will take a few years.

Therapy Dogs Reduce Pain in ER Patients

By Pat Anson, PNN Editor

Pet therapy has long been used in a variety of medical settings to help patients feel better – from nursing homes and hospice care to pediatric wards and cancer centers. And now, for the first time, there’s evidence that therapy dogs can significantly reduce pain, anxiety and depression in emergency department patients.

A Canadian research team at the University of Saskatchewan randomly selected nearly 200 ED patients who were waiting to be treated or admitted at Saskatoon's Royal University Hospital. Half of the participants spent 10 minutes with a therapy dog and its handler, while the other half received standard care without a dog visit.

The study findings, recently published in PLOS ONE,  showed that nearly half the patients visited by a therapy dog reported a decrease in pain (43%), with similar improvements in anxiety (48%), depression (46%) and overall well-being (41%). The dog visits had no significant effect on heart rate or blood pressure.

“Clinically significant changes in pain as well as significant changes in anxiety, depression and well-being were observed in the therapy dog intervention compared to control. The findings of this novel study contribute important knowledge towards the potential value of ED therapy dogs to affect patients’ experience of pain, and related measures of anxiety, depression and well-being,” wrote lead author Colleen Dell, PhD, a sociology professor at the University of Saskatchewan.

Pain is the most common reason that someone visits an emergency department, so the finding that therapy dogs can decrease pain levels is notable – particularly because most patients in the study (77%) did not receive any pain medication.

Many people with pain dread the idea of going to an emergency room, fearing that their pain won’t be treated properly. In a PNN survey of nearly 1,300 acute and chronic pain patients, over 80% said hospital staff are not adequately trained in pain management and over half rated the quality of their pain care in hospitals as poor or very poor. Nearly eight out of ten patients felt they were labelled as an addict or drug seeker by hospital staff.

Dell and her colleagues are well aware of the stress a pain patient can experience when visiting an emergency department, particularly in an era when the use of opioid medication is discouraged. Long waits, bright lighting and high noise levels may also make it difficult for ED patients to relax. They think therapy dogs could be useful in improving the patient experience.

“With adequate access to pharmaceutical pain management a concern for ED patients, as well as long wait times, it will be important to explore creative, non-pharmaceutical options,” said Dell. “Patient waiting has also been associated with negative emotional states and well-being in ED patients. Negative feelings, particularly anxiety and stress, can be intensified when patients encounter uncertainty regarding their pain.

“The role of therapy dog visits in decreasing patients’ perceived pain, whether as a distraction or by some other mode, is an important finding that should be examined further in both practice and research.”      

The benefits of having a pet are well known to most pet owners. A 2019 survey of over 2,000 older Americans found that pets helped them enjoy life, made them feel loved, kept them physically active and reduced stress. Pet ownership was particularly helpful to those who rated their health as fair or poor. More than 70 percent of those older adults said pets help them cope with physical or emotional problems, and nearly half (46%) said their pets help distract them from pain.

Drug Derived from Ticks Could Take Bite Out of Pain

By Pat Anson, PNN Editor

If you’ve experienced Lyme disease, probably the last place you’d look for pain relief is ticks. The insects are notorious for spreading Lyme, a bacterial illness that causes chronic fatigue, muscle and joint pain, cognitive issues and other symptoms that can last for years.  

But UK researchers say a protein found in tick saliva – called Votucalis – shows potential as a treatment for chronic pain. In experiments on laboratory animals, Votucalis provided pain and itch relief to mice subjected to neuropathic pain. Their findings were recently published in the journal Frontiers in Pharmacology.

“It is amazing that a protein found in the saliva of this tiny creature could prevent chronic pain and itching in people,” says co-author Ilona Obara, PhD, Director of Research in the School of Pharmacy at Newcastle University. “These are conditions that bring a huge amount of misery, and current medication displays limited efficacy, and can also often be detrimental to patients.

“Votucalis has already been tested in humans with other conditions, including conjunctivitis, without major side-effects, so the potential for this to be developed into a drug to tackle chronic pain and itching is definitely there.”

Obara began her research at Durham University with co-author Paul Chazot, PhD. Their research focused on tick saliva because it has pain relieving, anti-inflammatory and anti-coagulant effects on mammals. Ticks are parasitic blood feeders that rely on their “hosts” to be unaware that they have uninvited dinner guests.

Researchers found that Votucalis is particularly good at binding to histamine and preventing it from activating histamine cell receptors, resulting in reduced itching and pain sensations when a host animal is bitten.

“Our study is the first to show evidence of the anti-itch and pain relief potential of Votucalis, which is very exciting. We could be on the brink of discovering a viable alternative to opioid and gabapentinoid drugs,” said Chazot, an Associate Professor in the Department of Biosciences at Durham University.

The next step is to develop a drug delivery system to effectively administer Votucalis at the site of itch and pain. The research is being funded by the government of Saudi Arabia – where ticks are emerging as a public health problem -- and Akari Therapeutics, a pharmaceutical company that hopes to turn Votucalis into a treatment for neuropathic and inflammatory pain.

Unlike opioids, Votucalis does not enter the brain, which means it is not addictive and less likely to cause side effects.

“We are delighted to be working with Drs. Chazot and Obara on the pipeline drug Votucalis. The exciting new data in pain and itch supports the potential that the unique mode of action of Votucalis, inhibiting all four histamine receptors, opens exciting therapeutic opportunities in pain management and dermatology," Clive Richardson, CEO of Akari Therapeutics, said in a statement.

Akari is developing another drug derived from ticks – called nomacopan – for the treatment of a rare skin disease and ophthalmic conditions in the eye.  

Strict Low-Calorie Diet Reduces Fibromyalgia Symptoms

By Pat Anson, PNN Editor

Fibromyalgia patients with obesity experienced a significant reduction in pain and other symptoms after three weeks on a strict low-calorie diet, according to a new study that suggests limiting calories – not just weight loss – can have an analgesic effect.

Researchers enrolled nearly 200 patients diagnosed with fibromyalgia who were participating in a weight management program at the University of Michigan Health System. Participants had an average body mass index (BMI) of 41, which is considered severe obesity.

For 12 weeks, they were put on a very low energy diet (VLED) that limits bread, rice, potatoes and other foods that are high in carbohydrates. VLED is designed to shift the body away from using glucose in sweet or starchy foods to burning its own body fat for energy. Study participants were limited to just 800 calories a day, less than half the amount recommended for adult women and only a third of the amount recommended for men.

After just three weeks on the restricted diet, nearly three out of four participants (72%) experienced symptom reductions of 30% or more, regardless of the amount of weight lost. Patients who showed little or no improvement had a higher BMI at the start of the study and were more likely to have had a diagnosis of depression.

“Our results show, for the first time, that individuals following aggressive calorie restriction, ie, a VLED, had rapid and significant improvements in pain distribution and common pain-related comorbid symptoms and, importantly, prior to the achievement of significant weight loss,” researchers reported in the journal ACR Open Rheumatology.

“Furthermore, improvement at week 3 was strongly associated with improvement over the entire 12-week course of VLED, suggesting that patients who respond are likely to show these effects early in the process. These findings provide preliminary support for the hypothesis that calorie restriction, per se, can reduce pain and comorbid symptoms in individuals with obesity.”

Fibromyalgia is a poorly understood disorder characterized by widespread body pain, fatigue, poor sleep and depression. The FDA has approved three drugs to treat fibromyalgia -- duloxetine (Cymbalta), milnacipran (Savella) and pregabalin (Lyrica) -- but many patients say the drugs are ineffective and often have side effects.  

Previous studies have suggested that weight loss can help lower pain levels, but the improvement was thought to be caused by reduced stress on knees, hips and lower back – parts of the body that are weight-bearing.  

The new study suggests that a strict diet alone can significantly reduce fibromyalgia pain without major weight loss, but researchers caution that more studies are needed to fully understand the biological processes at work.

“The implications of this study suggest an early association between caloric restriction, through a VLED, and fibromyalgia symptoms. Although a larger study with a control group would be the next step in investigating this association, this provides important information for clinicians who counsel patients on alternatives to pharmacologic treatments for pain and other somatic symptoms,” researchers concluded.     

Many previous studies have shown that a low calorie diet can help reduce pain levels. A 2018 study at the University of Michigan found that obese patients on a low-calorie liquid diet for 12 weeks not only had lower pain levels in their knees and hips, but also in unexpected areas such as the abdomen, arm, chest and jaw. Study participants who lost 10% of their weight also reported better mental health, improved cognition and more energy.

Mindfulness Program Reduced Chronic Pain and Opioid Use

By Pat Anson, PNN Editor

A mindfulness therapy program reduced chronic pain and emotional distress in patients on long-term opioid therapy, in what’s being touted as the first randomized clinical trial to demonstrate the effectiveness of psychotherapy in reducing pain and opioid use simultaneously.

Researchers at the University of Utah enrolled 250 patients being treated for chronic pain at primary care clinics in the Salt Lake Valley. Most participants took oxycodone or hydrocodone, reported two or more painful conditions, and met the clinical criteria for major depression. Over two-thirds had also been diagnosed with opioid use disorder.

Study participants were randomly assigned to either a standard psychotherapy support group or a mindfulness program called Mindfulness-Oriented Recovery Enhancement (MORE). Both groups met for 8 weekly two-hour sessions. Patients in the MORE group were trained to meditate on their breathing and body sensations, and to practice 3 minutes of mindfulness before taking opioid medication -- focusing on whether their opioid use was due to drug craving or the need for pain relief.

The study findings, published in JAMA Internal Medicine, showed sustained and significant reductions in pain symptoms, depression and opioid use in the MORE group nine months after treatment ended. Researchers say 45% of MORE participants were no longer misusing opioids (compared to 24% in the support group) and 36% had cut their opioid use in half.

“MORE demonstrated one of the most powerful treatment effects I’ve seen,” lead author Eric Garland, PhD, director of the Center on Mindfulness and Integrative Health Intervention Development at the University of Utah, said in a press release. “There’s nothing else out there that works this well in alleviating pain and curbing opioid misuse.”

Garland believes the sustained benefits of MORE might be related to the program’s ability to restructure the way the brain processes rewards, helping patients shift from valuing the physical and psychological effects of drugs to valuing natural, healthy rewards like a beautiful sunset or the smile on the face of a loved one. 

“Remarkably, the effects of MORE seem to get stronger over time,” said Garland, who has been studying mindfulness for over a decade. “One possible explanation is that these individuals are integrating the skills they’ve learned through MORE into their everyday lives.”  

MORE participants are taught to reevaluate the experience of pain and opioid craving, “zooming in” on what they are feeling and breaking it down into different sensations like heat, tightness or tingling. They learn how those experiences change over time, and to adopt the perspective of an observer.

“Rather than getting caught up in the pain or craving, we teach people how to step back and observe that experience from the perspective of an objective witness,” Garland explained. “When they can do that, people begin to recognize that who they truly are is bigger than any one thought or sensation. They are not defined by their experiences of pain or craving; their true nature is something more.”

Garland said the findings are particularly noteworthy because many participants had multiple chronic pain conditions, were on high-opioid doses and also had psychiatric disorders. The average pain duration of participants at the start of the study was nearly 15 years and their average pain score was 5.5 on a 1 to 10 pain scale.

Natural Herbs for Intractable Pain Syndrome

By Dr. Forest Tennant, PNN Columnist 

Intractable Pain Syndrome (IPS) is defined as constant pain with cardiovascular, metabolic and hormonal complications. IPS is caused by neuroinflammation inside the brain and spinal cord (central nervous system or CNS) that comes from excess electromagnetic energy generated by a painful disease or injury.

Excess electromagnetic energy activates an immune cell in the CNS called “microglia” to produce inflammation that then destroys tissue in the CNS. Unfortunately, tissue destroyed by inflammation impairs or damages the normal CNS mechanisms that shut off or cause pain to cease. A person may, therefore, develop constant (24/7) pain that overstresses the cardiovascular, metabolic and hormonal systems.

Tissue destruction in the CNS is well documented by brain scans. This relatively recent understanding of how neuroinflammation destroys CNS tissues and causes constant pain is arguably the most important discovery for pain treatment in the 21st Century. Why? We now have some ideas on how to treat IPS that can possibly cure or at least permanently reduce pain rather than just provide temporary, symptomatic relief. 

Treating CNS Inflammation 

When someone develops IPS, it is human nature to seek immediate pain relief and ignore its basic cause. If you have constant (24/7) pain, however, one must accept the fact that you have inflammation in the CNS that must be suppressed. Otherwise, you can reasonably assume that the pain will get worse.  

While research has documented that CNS inflammation may spread, it is unknown whether it ever “burns out.” As of yet, there is no blood or x-ray test to know if “burn out” may occur. This means that every person with IPS must take one or more anti-inflammatory agents to stop further tissue destruction and the worsening of pain. 

A problem when suppressing inflammation in the CNS is that only a few of the anti-inflammatory agents which are commercially available cross the blood brain barrier and enter the spinal fluid in sufficient amounts to be effective. This includes the non-specific anti-inflammatory drugs (NSAIDs) and corticosteroids.  

Benefits of Natural Herbal Products

Interestingly, natural products such as botanicals, herbs, enzymes and hormones tend to cross the blood brain barrier and provide anti-inflammatory activity. A well-known common example is aspirin (acetylsalicylic acid), which is derived from willow tree bark.

This has caused a great deal of interest in the use of natural products for suppression of CNS inflammation. Several research studies in both laboratory tests and animals have found that some natural agents do indeed suppress CNS inflammation.

To date, research has identified five herbs that suppress CNS inflammation. There are likely other natural products that suppress CNS inflammation, but this list is a good start:

1. Ginseng

2. Curcumin

3. Resveratrol

4. Ginger

5. Fisetin

Currently, there are very few controlled blind studies in humans to demonstrate the effectiveness of these herbal products. Personally, I have often seen considerable effectiveness of natural products in reducing the pain of IPS. Other anecdotal reports from patients and doctors are also starting to accumulate.

Precise dosages are unknown, but the manufacturer of each herbal product will have some starting instructions on the label. Herbal agents appear quite safe and have few reported side effects. Herbs can be taken with corticosteroids, opioids, naltrexone, electrical stimulators, neuropathic agents, and essentially all medication used for treatment of IPS.

At this time, we believe there is enough research and clinical experience to recommend both herbal, non-prescription as well as prescription anti-inflammatory agents to assist treatment of IPS. The time has come to treat IPS with a broader-based approach rather than just the use of symptomatic pain relievers.

Based on our current knowledge, IPS will likely get worse unless a person’s treatment program includes agents that suppress CNS inflammation.

Forest Tennant, MD, DrPH, MPH is retired from clinical practice but continues his research on the treatment of arachnoiditis and intractable pain at the Arachnoiditis Research and Education Project. The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

FDA Urged to Regulate Poppy Seeds

By Pat Anson, PNN Editor

A consumer advocacy group is once again calling on the Food and Drug Administration to establish and enforce regulations that limit opiate contamination of poppy seeds.

Over a year ago, the Center for Science in the Public Interest (CPSI) petitioned the FDA to set a safe threshold for opiate alkaloids in imported poppy seeds, most of which come from Afghanistan. The tiny black seeds can become contaminated with trace amounts of codeine, morphine and other opiates when they are harvested from opium poppies.

Washed poppy seeds are often found in baked goods, but drug users have found they can use unwashed seeds to make a potent homemade tea. PNN has reported that some pain sufferers use the tea as an analgesic, although the bitter brew is mostly consumed by people who simply want to get high.     

In its petition, CSPI cited a study estimating that 19 people in the U.S. suffered fatal overdoses involving poppy seeds in recent years.

In a letter recently sent to the FDA Center for Food Safety and Applied Nutrition, CSPI renewed its call for the agency to take action to prevent more deaths.

“The time is overdue for the FDA to establish standards that will protect U.S. consumers from ingesting dangerous levels of opiates through the food supply,” wrote Peter Lurie, MD, President of CSPI wrote.  

The European Food Safety Authority established maximum levels of morphine and codeine in poppy seeds last year, which are scheduled to take effect in July.

In 2019, the U.S. Drug Enforcement Administration classified unwashed poppy seeds as a Schedule II controlled substance and closed a loophole that allowed them to be sold legally in the U.S.  

Enforcement actions since then have been scant. In October 2021, federal regulators filed a civil forfeiture action against an Oklahoma bakery to halt the sale of unwashed seeds. But within a few weeks the company was selling them again on its website, with a disclaimer saying the seeds “may contain trace amounts of opiate alkaloid residue” and should be thoroughly washed before consuming.

To date, the only action the FDA has taken on the CSPI petition was to post a notice in the Federal Register asking for public comment on the need for poppy seed regulation. Over 3,000 people responded, most of them supporting the petition. Asked to comment on the CSPI’s new letter, an FDA spokesperson said the issue remains under review.

“As part of our review of CSPI’s petition, we are considering the points raised in the petition and the over 3,200 comments submitted to the docket. The FDA has been engaging with other federal partners in this effort to help protect the public’s health,” the spokesperson told PNN in an email. 

To be clear, consuming unwashed poppy seeds is risky. Home brewers usually have no way of knowing where the seeds came from or how heavily they are contaminated with opiates. The Internet is filled with cautionary stories from illicit drug users who nearly overdosed or became addicted to the tea and went into withdrawal when they tried to taper.

“I woke up yesterday with a migraine (that’s typical when I quit) and by the afternoon the withdrawals had started: sweating, anxious, can’t get comfortable, want to crawl out of my skin,” a person recently posted on Reddit. “I want to get off this merry go round. I feel like my brain is totally normal except that little piece that is constantly scheming where my next opiates are coming from. They don’t even make me high, they just make me feel ‘normal’, so what’s the point? I want to be free of this.”

For people in pain, there’s an added risk to poppy seeds. A recent study found that consuming just few seeds in a muffin or bagel could result in a positive drug test – a finding that could get a patient taken off opioids or dismissed by their doctor.

Only 1 in 7 Chronic Pain Patients Use Opioids

By Pat Anson, PNN Editor

Have you tried physical therapy? What about yoga or Tai Chi? Did massage help you feel better?

Just about everyone in chronic pain has been asked that by family members, friends, doctors and sometimes even complete strangers.  The questions are innocent enough and usually well-meaning, but they often imply that a pain sufferer hasn’t looked beyond opioids for pain relief.

A new study shows that most people with chronic pain make extensive use of non-opioids and other “alternative” pain treatments – and that it’s relatively rare for a patient to only use opioids for pain relief.

The findings, published in JAMA Network Open, are based on answers to the 2019 National Health Survey by nearly 32,000 U.S. adults with chronic pain. The 2019 survey was the first to ask people about their use of 11 pain management techniques during the previous three months.

It turns out most people with chronic pain (54.7%) only used non-opioid pain management. And nearly a third (30.2%) used no pain therapy whatsoever. The rest either used opioids alone (4.4%) or a combination of opioids with one or more alternative treatments (10.7%).

That means only about 1 in every 7 adults with chronic pain even use opioids – a startling number when you consider the constant harping from anti-opioid activists and public health officials about how opioids are “overprescribed” in the U.S.   

“This study found that adults with chronic pain in the US use a variety of pain management techniques, including opioids,” wrote lead author Cornelius Groenewald, MB, a pediatric anesthesiologist and associate professor at the University of Washington School of Medicine. “Nonpharmacologic and nonopioid pharmacologic therapies are preferred treatments for chronic pain, and it is encouraging to note that most adults with chronic pain use a combination of various nonopioid modalities for treatment.”

Alternative Chronic Pain Therapies Used in 2019

• 18.8% Physical Therapy

• 17.6% Massage

• 15.6% Meditation or Relaxation Techniques

• 11.6% Spinal Manipulation or Chiropractic Care

• 8.5% Yoga or Tai Chi

• 5.1% Pain Self-Management Workshops

•  3.8% Psychological or CBT Therapy

• 1.8% Peer Support Group      

Nearly 40% of chronic pain sufferers reported using other therapies that were not listed in the survey. That may include treatments such as cannabis, kratom, medical devices, acupuncture or even ice packs. It would be good to include more of those options in future surveys.

Groenewald and his colleagues were disappointed that so few people used psychological techniques such as cognitive behavioral therapy (CBT), which was the only alternative pain therapy that they said was “underused.”   

The researchers found that complementary, psychological or psychotherapeutic therapies were more likely to be used by younger adults, females and people with more education. Adults using physical, occupational or rehabilitative therapies were more likely to be older, female, highly educated and have medical insurance.

Neuromodulation Device Effective for Most Migraine Sufferers

By Pat Anson, PNN Editor

A wearable neuromodulation device significantly reduced headache pain in nearly two-thirds of migraine sufferers, according to a new study. About one in four participants (22.6%) who used the device had no migraine pain after two hours.

The study findings, published in the journal Frontiers in Pain Research, are based on an analysis of over 23,000 remote electrical neuromodulation (REN) treatments with Nerivio, a device worn on the upper arm that uses mild electrical pulses to disrupt pain signals.

It’s important to note the study was designed and funded by Theranica Bio-Electronics, Nerivio’s manufacturer. Three of the five co-authors are Theranica employees.

“The current analysis of a very large group of patients, over a long period of time and multiple treatments, reinforces that REN provides a safe, efficacious and stable treatment option for acute treatment of migraine, both as a standalone and as an adjunct therapy. This is a very important component in the migraine therapy toolbox," lead author Jessica Ailani, MD, Director of the MedStar Georgetown Headache Center and Professor of Clinical Neurology, said in a press release.

Nerivio is controlled by a smartphone app that allows patients to set the intensity of their 45-minute treatments at the onset of a migraine. The app also has a migraine diary that allows patients and their doctors to track the effectiveness of REN.

It is from this app that study data was collected from 12,151 U.S. patients from 2019 to 2021. Most had been prescribed REN by headache specialists, indicating their migraines were difficult to treat with pain medication alone. During the study, about two-thirds of patients only used REN, with the remainder continuing to use over-the-counter or prescription medications.

"To the best of our knowledge, this study is the largest prospective real-world evidence analysis of a migraine device to date," said Alon Ironi, CEO of Theranica.

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, visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Although migraine sufferers have many new treatments available, such as CBD oil and calcitonin gene-related peptide (CGRP) inhibitors, many find them too expensive or ineffective. Theranica hopes Nerivio can help fill the treatment gap, either as a standalone replacement for medication or as an adjunct.

"While some people with migraine get relief from prescribed or even over-the-counter medications, others do not respond to medications, or cannot tolerate their side effects. There are also people who cannot use medications due to contraindications or being at risk of drug-drug interactions or medication overuse headache,” Ailani said.

The FDA approved Nerivio as a treatment for acute migraine in adults in 2019. Last year the label was expanded to include children over the age of 12 with episodic or chronic migraine. Over 25,000 people in the U.S. have used the device, according to Theranica.

Nerivio is only available by prescription. 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.  

Experimental Gene Therapy Could Cure Sickle Cell Disease

By Pat Anson, PNN Editor

Experimental gene therapy is helping sickle cell patients develop normal red blood cells and could potentially be a cure for the disease, according to research recently published in The New England Journal of Medicine.

In early-stage Phase 1 and 2 clinical trials at the University of Alabama at Birmingham, 25 patients treated with a gene therapy called LentiGlobin produced stable amounts of red blood cells containing hemoglobin after a single infusion. 

Sickle cell disease is a genetic disorder that causes red blood cells to form in a crescent or sickle shape, which creates painful blockages in blood vessels that can lead to anemia, infections, strokes and organ failure. About 100,000 Americans live with sickle cell disease, primarily people of African or Hispanic descent.

Unlike other gene therapies that edit or silence genes, LentiGlobin adds a modified gene that reprograms the diseased blood cells.  

“In this therapy, we do not change or edit the gene that causes sickle cell disease,” says Julie Kanter, MD, director of the UAB Adult Sickle Cell Clinic. “Instead, we use a viral vector to deliver a new gene that will make a healthy hemoglobin — a beta hemoglobin — into the stem cell. This is like coding new instructions into the cell.”

The new hemoglobin -- called HbAT87Q -- is slightly different from regular hemoglobin and is less likely to cause red blood cells to be misshaped.  The HbAT87Q can also be measured more accurately inside the cell, allowing doctors to know how much of the new hemoglobin a patient is making on their own.

Although the gene therapy looks promising, researchers say more advanced studies are needed to make sure LentiGlobin is safe and effective long-term. 

“In an earlier part of this study, we were not able to get enough of the new gene into each cell,” explained Kanter. This caused the blood cells to be stressed and for some patients to still have symptoms of sickle cell disease. Two patients in the initial group developed leukemia.  

“We need to see that we have fixed this problem, says Kanter. “We also need to make sure this procedure both reduces pain/stops all pain crisis and prevents organ damage from sickle cell. This will take time. We will have to watch people for the next two to 15 years and measure their organ function compared to those who did not get this therapy.”

A 2020 report by the National Academies of Sciences, Engineering, and Medicine called for major changes in the way sickle cell disease is treated in the U.S. Compared to other chronic illnesses, stem cell disease has received little attention from the healthcare community, resulting in a lag in the development of new treatments.

Many stem cell patients also feel stigmatized when they have a pain flare and go to an emergency room, because ER staff are often ignorant about the disease and believe patients are seeking drugs.

“People with sickle cell disease have endured unnecessary hardship for more than 100 years. They have fewer medications and therapies than many other diseases and have received much less attention and funding. We need new and better options for people with sickle cell disease,” said Kanter.

Bone marrow and stem cell transplants are currently the only cures for sickle cell disease, but it’s often difficult to find good donors. Fewer than one in five people with the disease have compatible donors.

Spending Time in Nature Can Reduce Chronic Pain

By Gabriella Kelly-Davies, PNN Columnist

A few months ago, I took part in a panel discussion with three other women who live with migraine or chronic headaches. One speaker, Australian journalist Sarah Allely, described how immersing herself in nature helped to relieve her debilitating headaches, anxiety and depression after a mild traumatic brain injury. It also drastically improved her focus and concentration.

Sarah’s brain injury occurred in 2015, when a passing car knocked her off her bicycle. Afterwards, a headache erupted in the base of her skull whenever she tried to read, write, watch television, or listen to music. She also struggled to concentrate and couldn’t work as a journalist for eight months.

Noisy environments such as bars, cafes and social gatherings that for years had energized Sarah, became unbearable. Despairing, she asked her medical team for advice. Her doctors admitted there wasn’t much they could do and suggested she learn to accept the situation. Sarah’s spirit sank as she contemplated a bleak future without all the things that had previously given her purpose and pleasure.

But that all changed when her friends invited her on a bush walk.

While trekking through the bush, Sarah’s headache lifted. So did her anxiety and depression. She wondered whether it was a fluke or if spending time in nature had reduced her symptoms.

During the following weeks, Sarah visited local bushland whenever possible. To her surprise, every time she did this, her headache, anxiety and depression eased. Intrigued, she wondered whether going to a local park or sitting in her garden would have a similar effect. She tried it. To her amazement, it worked!

A while later she stumbled across some magazine articles about research around the healing powers of nature. Curious about why her symptoms eased whenever she spent time in nature, Sarah decided to make an audio documentary. She wanted to understand the science behind her experience and the “optimum dose of nature” to relieve her physical and emotional pain.

During her research, Sarah came across several American scientists who were studying the science underpinning the healing effects of nature. Excited, she interviewed them, turning the conversations into six episodes of a podcast series she named Brain on Nature.

In the free podcast, Sarah shares her experiences discovering the healing powers of the natural world. Each episode follows her quest to discover why the natural environment changed her brain, helping her recover from a brain injury.

Seeking Connections With Nature

The scientists Sarah interviewed told her they were asking the same questions as her. Their studies found spending time in nature improved psychological and physical health, but they couldn’t pinpoint the precise reason for this response. Still, they were confident certain theories did help explain what was happening.

One of these theories is called biophilia, a belief that humans have an innate tendency to seek connections with nature. But for many of us living in bustling urban settings, constant traffic noise, bright lights, sirens, flashing billboards and yelling are the norm, and connecting with nature is a dream rather than a reality.

Instead of relaxing or exercising in a natural environment, we multitask, work on computers, talk on mobile phones, scroll through social media and send text messages. Living this way increases our stress levels, and for people with chronic pain, this can mean more pain.

But there is good news. Several studies show that when people turn off their electronic devices and sit in a quiet garden or stroll in a park, they feel refreshed and relaxed.

Pain specialists know that when a person living with chronic pain is calm, the volume of pain signals racing through their nervous systems is less than when they are anxious, angry or upset. So it makes sense that pain could reduce after spending time in a relaxing environment such as a garden or park.

Another possible explanation for Sarah’s experiences comes from Rachel and Stephen Kaplan’s Attention Restoration Theory. The Kaplans propose that exposure to nature is not only enjoyable but also relaxing and revitalizing. In Sarah’s case, whenever she spends time in the mountains on a weekend, she remains headache-free the following week. Her focus and concentration are also better. 

Fortunately, benefiting from the healing effects of nature is not about climbing Mount Everest or going on three-day treks in the forest. It can be a 10-minute walk in a local park or sitting in the garden smelling the flowers.

Once she understood the natural world was helping her injured brain to recover, Sarah felt compelled to share her learnings with others whose health might benefit from a dose of nature.  

“No one in the medical world suggested immersing myself in nature could reduce my symptoms,” she says. “But it works. I want others to know about it so they can try it for themselves.”

Hundreds of thousands of people around the world have listened to Brain on Nature and Sarah says their response is overwhelmingly positive.

“Two years after launching Brain on Nature, I’m still getting emails every week from people who say their life changed after listening to the podcast,” Sarah says. “I’m delighted it continues to have a positive impact and my search for answers has helped so many people.”

Sarah accepts some people might be skeptical about her belief in the natural world’s healing effects, especially if they have lived with chronic pain for several years and nothing has helped. She understands this response, but encourages anyone in pain to try a dose of nature for themselves to see if it eases their pain or improves their mood.

“When your pain is bad or you’re feeling grumpy, anxious or depressed, take yourself for a walk in the garden or a park,” Sarah suggests. “Put your phone on flight mode and see how you feel when you come back. Do you feel different? I challenge you to say spending time in nature doesn’t make any difference. So far I haven’t met anyone who can say that.”

While immersing ourselves in nature might not be a cure for chronic pain, it’s a powerful option in our pain management toolbox. Since learning about this approach, I now turn off my phone whenever we go for our morning stroll. Instead of feeling harassed by too many phone calls and text messages during our walk, I now feel relaxed and centered. And when I’m calm, I have less pain. I hope you do too.

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