Experimental Implant Uses Coolant to Numb Nerve Pain

By Pat Anson, PNN Editor

Applying ice on inflamed tissues and sore muscles is one of the oldest ways to relieve pain and promote healing.  Researchers at Northwestern University are taking that tried-and-true method a step further, with the development of a small, flexible implant that can alleviate pain by literally cooling nerves.

Researchers believe the experimental implant could be most beneficial to patients who undergo surgeries, nerve grafts or even amputations. Surgeons could implant the device during the procedure to help patients manage post-operative pain on demand without the use of drugs.

“As engineers, we are motivated by the idea of treating pain without drugs — in ways that can be turned on and off instantly, with user control over the intensity of relief,” says John Rogers, PhD, Professor of Materials Science and Engineering at Northwestern and lead author of a study published in the journal Science.

“The technology reported here exploits mechanisms that have some similarities to those that cause your fingers to feel numb when cold. Our implant allows that effect to be produced in a programmable way, directly and locally to targeted nerves, even those deep within surrounding soft tissues.”

In experiments on laboratory rats, Rogers and his colleagues demonstrated that the implants can rapidly cool peripheral nerves to relieve neuropathic pain.

As thick as a sheet of paper, at its widest point the implant is 5 millimeters wide – about the size of the eraser on a pencil. One end is curled into a cuff that can softly wrap around a nerve, without the need for sutures to hold it in place.

“If you think about soft tissues, fragile nerves and a body that’s in constant motion, any interfacing device must have the ability to flex, bend, twist and stretch easily and naturally,” said Rogers.

NORTHWESTERN UNIVERSITY

To induce cooling, the device contains tiny microfluid channels. One channel contains a liquid coolant (perfluoropentane), while a second channel contains dry nitrogen. When the liquid and gas flow into a shared chamber, a reaction occurs that causes the liquid to evaporate and cool. A tiny sensor in the implant monitors the temperature of the nerve to ensure that it’s not getting too cold, which could cause tissue damage.

“As you cool down a nerve, the signals that travel through the nerve become slower and slower — eventually stopping completely,” said coauthor Matthew MacEwan, PhD, from Washington University School of Medicine in St. Louis. “We are specifically targeting peripheral nerves, which connect your brain and your spinal cord to the rest of your body. These are the nerves that communicate sensory stimuli, including pain. By delivering a cooling effect to just one or two targeted nerves, we can effectively modulate pain signals in one specific region of the body.”

An external pump allows patients to remotely activate the implant and increase or decrease its intensity. Because the device is biocompatible and water-soluble, it will naturally dissolve and absorb into the body over the course of days or weeks — bypassing the need for surgical extraction.

Other cooling therapies have been tested experimentally, but have limitations. Instead of targeting specific nerves, they cool large areas of tissue, potentially leading to side effects such as tissue damage and inflammation.

“You don’t want to inadvertently cool other nerves or the tissues that are unrelated to the nerve transmitting the painful stimuli,” MacEwan said. “We want to block the pain signals, not the nerves that control motor function and enables you to use your hand, for example.”

UK Warns Pregnant Women About Taking Pregabalin

By Pat Anson, PNN Editor

Health officials in the UK are warning women of childbearing age that pregabalin (Lyrica), a drug commonly prescribed for pain, anxiety and epilepsy, raises the risk of major birth defects.

A recent study in four Nordic countries of over 2,700 pregnancies found that 5.6% of babies born to women who took pregabalin in the first three months of pregnancy had birth abnormalities. That compares to 4.1% of babies whose mothers did not use pregabalin.  

“The study showed that taking pregabalin during early pregnancy was associated with a slightly increased chance of having a baby who is born with a physical birth abnormality. It is important to note that this study could not show that pregabalin was the cause of the physical birth abnormalities,” the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) said in a new safety alert.

The birth defects associated with pregabalin primarily involved the nervous system, eyes, face, urinary system and genitals. The MHRA – which regulates drugs in the UK – cautioned pregnant women not to stop taking pregabalin without talking to a doctor first.

“If you think you may be pregnant and are currently taking pregabalin, you should set up an appointment with your GP, specialist or nurse at your earliest opportunity, to discuss any concerns you may have. However, do continue to take pregabalin as prescribed until you can speak to them,” the MHRA alert said. “Untreated epilepsy, pain, or anxiety could be harmful to you and your unborn baby. It is important that you talk to your healthcare professional before stopping pregabalin or making any changes to your usual medicines.”

An international study in 2016 also linked pregabalin to birth defects. Women taking pregabalin were found to be six times more likely to have a baby with a major birth defect, including abnormalities in the heart, central nervous system (CNS) and other organs.

Pregabalin Concerns

In recent years, pregabalin has come under increased scrutiny in the UK.  In 2021, the MHRA said pregabalin was associated with serious breathing problems in people over age 65 and in patients with compromised respiratory systems.

Doctors in Northern Ireland were also told last year not to prescribe pregabalin for neuropathic pain due to a “significant increase” in drug-related deaths involving the drug.

In 2019, pregabalin and gabapentin (Neurontin) were both rescheduled as Class C drugs in the UK due to a rising number of overdose deaths. Health experts said the medications cause “an elevated mood in users” and could have serious side effects when combined with other drugs.

Lyrica and Neurontin are two of Pfizer’s top selling drugs and generate billions of dollars in annual sales. They belong to a class of nerve medication called gabapentinoids that were originally developed to treat seizures, but are now widely prescribed as an alternative to opioid painkillers. A 2019 study found little evidence that gabapentinoids should be used to treat pain and said their effectiveness was often exaggerated by prescribing guidelines.

In the United States, where Lyrica is approved for fibromyalgia, neuropathic pain, seizures and postherpetic neuralgia, the FDA’s lengthy warning label states that “there are no adequate and well-controlled studies with Lyrica in pregnant women,” but at the same time cautions that “Lyrica may harm your unborn baby.”  

An earlier warning label said it was “not known if Lyrica will harm your unborn baby.”

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.

Closed Pain Clinics Were ‘Always Pushing Injections’

By Anna Maria Barry-Jester and Jenny Gold, Kaiser Health News

On May 13 of last year, the cellphones of thousands of California residents undergoing treatment for chronic pain lit up with a terse text message: “Due to unforeseen circumstances, Lags Medical Centers will be closing effective May 19, 2021.”

In a matter of days, Lags Medical, a sprawling network of privately owned pain clinics serving more than 20,000 patients throughout the state’s Central Valley and Central Coast, would shut its doors. Its patients, most of them working-class people reliant on government-funded insurance, were left without ready access to their medical records or handoffs to other physicians.

Many patients were dependent on opioids to manage the pain caused by a debilitating disease or injury, according to alerts about the closures that state health officials emailed to area physicians. They were sent off with one final 30-day prescription, and no clear path for how to handle the agony — whether from their underlying conditions or the physical dependency that accompanies long-term use of painkillers — once that prescription ran out.

The closures came on the same day that the California Department of Health Care Services suspended state Medi-Cal reimbursements to 17 of Lags Medical’s 28 locations, citing without detail “potential harm to patients” and an ongoing investigation by the state Department of Justice into “credible allegations of fraud.”

In the months since, the state has declined to elaborate on the concerns that prompted its investigation. Patients are still in the dark about what happened with their care and to their bodies.

photo by Kathleen Hayden (KHN)

Even as the government remains largely silent about its investigation, interviews with former Lags Medical patients and employees, as well as KHN analyses of reams of Medicare and Medi-Cal billing data and other court and government documents, suggest the clinics operated based on a markedly high-volume and unorthodox approach to pain management. This includes regularly performing skin biopsies that industry experts describe as out of the norm for pain specialists, as well as notably high rates of other sometimes painful procedures, including nerve ablations and high-end urine tests that screen for an extensive list of drugs.

Those procedures generated millions of dollars in insurer payments in recent years for Lags Medical Centers, an affiliated network of clinics under the ownership of Dr. Francis P. Lagattuta. The clinics’ patients primarily were insured by Medicare, the federally funded program for seniors and people with disabilities, or Medi-Cal, California’s Medicaid program for low-income residents.

Taken individually, the fees for each procedure are not eye-popping. But when performed at high volume, they add up to millions of dollars.

Take, for example, the punch biopsy, a medical procedure in which a circular blade is used to extract a sample of deep skin tissue the size of a pencil eraser. The technique is commonly used in dermatology to diagnose skin cancer but has limited use in pain management medicine, usually involving a referral to a neurologist, according to multiple experts interviewed. These experts said it would be unusual to use the procedure as part of routine pain management.

KHN used Medi-Cal records to assess the volume of services performed across the entire chain. But the state could not provide totals for how much Lags Medical was reimbursed because of California’s extensive use of managed-care plans, which do not make their reimbursement rates public. Where possible, KHN estimated the worth of Medi-Cal procedures based on the set rates Medi-Cal pays traditional fee-for-service plans, which are public.

Lags Medical clinics performed more than 22,000 punch biopsies on Medi-Cal patients from 2016 through 2019, according to state data. Medi-Cal reimbursement rates for punch biopsies changed over time. In 2019 the state’s reimbursement rate was more than $200 for a set of three biopsies performed on patients in fee-for-service plans.

Laboratory analysis of punch biopsies was worth far more. Lags Medical clinics sent biopsies to a Lags-affiliated lab co-located at a clinic in Santa Maria, according to medical records and employee interviews. From 2016 through 2019, Lags Medical clinics and providers performed tens of thousands of pathology services associated with the preparation and examination of tissue samples from Medi-Cal patients, according to state records. The services would have been worth an estimated $3.9 million using Medi-Cal’s average fee-for-service rates during that period.

In that same period, Medicare reimbursed Lagattuta at least $5.7 million for pathology activities using those same billing codes, federal data shows.

‘Assembly Line’ Pain Care

Much of the work at Lags Medical was performed by a relatively small number of nurse practitioners and physician assistants, each juggling dozens of patients a day with sporadic, often remote supervision by the medical doctors affiliated with the clinics, according to interviews with former employees. Lagattuta himself lived in Florida for more than a year while serving as medical director, according to testimony he provided as part of an ongoing malpractice lawsuit that names Lagattuta, Lags Medical, and a former employee as defendants.

Former employees said they were given bonuses if they treated more than 32 patients in a day, a strategy Lagattuta confirmed in his deposition in the malpractice lawsuit. “If they saw over, like, 32 patients, they would get, like, $10 a patient,” Lagattuta testified.

The lawsuit, filed in Fresno County Superior Court, accuses a Lags Medical provider in Fresno of puncturing a patient’s lung during a botched injection for back pain. Lagattuta and the other named defendants have denied the incident was due to negligent treatment, saying, in part, the patient consented to the procedure knowing it carried risks.

Hector Sanchez, the nurse practitioner who performed the injection and is named in the lawsuit, testified in his own deposition that providers at the Lags Medical clinic in Fresno each treated from 30 to 40 patients on a typical workday.

According to Sanchez’s testimony and interviews with two additional former employees, Lags Medical clinics also offered financial bonuses to encourage providers to perform certain medical procedures, including punch biopsies and various injections. “We were incentivized initially to do these things with cash bonuses,” said one former employee, who asked not to be named for fear of retribution. “There was a lot of pressure to get those done, to talk patients into getting these done.”

In his own deposition in the Fresno case, Lagattuta denied paying bonuses for specific medical procedures.

‘Injections, Injections, Injections’

Interviews with 17 former patients revealed common observations at Lags Medical clinics, such as crowded waiting rooms and an assembly-line environment. Many reported feeling pressure to consent to injections and other procedures or risk having their opioid supplies cut off.

Audrey Audelo Ramirez said she had worried for years that the care she was receiving at a Lags Medical clinic in Fresno was subpar. In the past couple of years, she said, there were sometimes so many patients waiting that the line wrapped around the building.

Ramirez, 52, suffers from trigeminal neuralgia, a rare nerve disease that sends shocks of pain across the face so severe it’s known as the “suicide disease.” Over the years, Lags Medical had taken over prescribing almost all her medications. This included not only the opioids and gabapentin she relies on to endure excruciating pain, but also drugs to treat depression, anxiety, and sleep issues.

Ramirez said she often felt pressured to get procedures she didn’t want. “They were always just pushing injections, injections, injections,” she said. She said staffers performed painful punch biopsies on her that resulted in an additional diagnosis of small fiber neuropathy, a nerve disorder that can cause stabbing pain.

She was among numerous patients who said they felt they needed to undergo the recommended procedures if they wanted continued prescriptions for their pain medications. “If you refuse any treatment they say they’re going to give you, you’re considered noncompliant and they stop your medication,” Ramirez said.

She said she eventually agreed to an injection in her face, which she said was administered without adequate sedation. “It was horrible, horrible,” she said. Still, she said, she kept going to the office because there weren’t many other options in her town.

Lagattuta, through his lawyer, declined a request from KHN to respond to questions about the care provided at his clinics, citing the state investigation. “Since there is an active investigation, Dr. Lagattuta cannot comment on it until it is completed,” attorney Matthew Brinegar wrote in an email. Lagattuta’s license remains in good standing, and he said in his deposition in the Fresno lawsuit that he is still seeing patients in California.

Experts interviewed by KHN noted that medical procedures such as injections can have a legitimate role in comprehensive pain management. But they also spoke in general terms about the emergence of a troubling pattern at U.S. pain clinics involving the overuse of procedures. In the 1990s and early 2000s, problematic pain clinics hooked patients on opioids, then demanded cash to continue prescriptions, said Dr. Theodore Parran, who is a professor of medicine at Case Western Reserve University and has served as an expert witness in federal investigations into pain clinics.

“What has replaced them are troubled pain clinics that hook patients with the meds and accept insurance, but overuse procedures which really pay well,” he said. For patients, he added, the consequences are not benign.

“I mean they are painful,” he said. “You’re putting needles into people.”

Cash Bonuses for Procedures

Before moving to California in 1998, Dr. Francis Lagattuta lived in Illinois and worked as a team doctor for the Chicago Bulls during its 1995-96 championship season. Out West, he opened a clinic in Santa Maria, a Latino-majority city along California’s Central Coast known for its strawberry fields, vineyards, and barbecue. From 2015 to 2020, the chain grew from a couple of clinics in Santa Barbara County to dozens throughout California, largely in rural areas, as well as far-flung locations in Washington state, Delaware, and Florida.

The California portion of the chain is organized as more than two dozen corporations and limited liability corporations owned by Lagattuta. His son, Francis P. Lagattuta II, was a manager for the company.

On the Lags Medical website and in conversation with employees, the elder Lagattuta claimed he was on the vanguard of diagnosing and treating small fiber neuropathy. Much of the website has now been taken down. But pages available via an archival site claim he had pioneered a three-pronged approach to pain management that made minimal use of opioids and surgeries, instead emphasizing testing, injections, mental health, diet, and exercise.

“In keeping with his social justice values, Dr. Lagattuta plans to share these findings to the rest of the world, hopefully to help solve the opioid crisis, and end suffering for millions of people struggling with pain,” touted a biography once highlighted on the website.

Dr. Francis Lagattuta (Twitter)

Numerous Lags Medical patients interviewed by KHN said that even when they were given punch biopsies and a subsequent diagnosis of neuropathy, their treatment plan continued to involve high doses of opioid medications.

Dr. Victor C. Wang, chief of the division of pain neurology at Brigham and Women’s Hospital in Boston, said punch biopsies are occasionally used in research but are not a standard part of pain medicine. Instead, small fiber neuropathy is usually diagnosed with a simple clinical exam.

“The treatment is going to be the same whether you have a biopsy or not,” said Wang. “I always tell the fellows, you can do this test or that one, but is it really going to change the management of the patient?”

Ruby Avila, a mother of three in Visalia, remembers having the punch biopsies done at least three times during her four years as a Lags Medical patient. “I have scars down my leg,” she said. Each time, she said, providers removed a set of three skin specimens that were used to diagnose her with small fiber neuropathy.

Avila, 37, who has lived with pain since childhood, had found it validating to finally have a diagnosis. But after learning more about how common the biopsies were at Lags Medical, she was shaken. “It’s overwhelming to hear that they were doing it on a lot of people,” she said.

Sanchez, the nurse practitioner named in the Fresno lawsuit, spoke of other procedures that garnered bonuses: “Trigger point injections, knee injections, hip injections, foot injections for plantar fasciitis and elbow injections” all qualified for $10 bonuses, he said in his testimony.

Two former employees, who asked not to be named, echoed Sanchez, saying they were incentivized to do certain procedures, including injections and punch biopsies.

In his testimony in the Fresno case, Lagattuta denied paying bonuses for procedures. “It was only for the patients,” he said. “We never did it based on procedures.”

Incentive systems for a specific procedure are “completely unethical,” said Dr. Michael Barnett, an assistant professor of health policy at Harvard. “It’s like giving police officers a quota for speeding tickets. What do you think they’re going to do? I can’t think of any justification.”

Dr. Carl Johnson, 77, is a pathologist who directed Lags Medical’s Santa Maria lab from 2018 to 2021. Johnson said the only specimens he looked at came from punch biopsies, the first time in his long career as a pathologist that he had been asked to run such an analysis. On an average day, he said, he examined the slides of about 40 patients, searching for signs of small fiber neuropathy. Lagattuta gave him papers to read on peripheral neuropathy and assured him they were on the cutting edge of care for pain patients.

Johnson said he “never thought there was anything untoward going on” until he arrived on his last day and was told to pack up his belongings because the entire operation was shutting down.

Nerve Ablations and Drug Tests

Lags Medical performed other procedures at rates that also set them apart. From 2015 through 2020 — the span for which KHN had state data — Lags Medical performed more than 24,000 nerve ablations, a procedure in which part of a nerve is destroyed to reduce pain, on Medi-Cal patients. That’s more than 1 in 6 of all nerve ablations billed through Medi-Cal during that period.

An analysis of federal data also shows Lagattuta was an outlier. For example, in 2018 he billed Medicare for nerve ablations more often than 88% of the doctors in his field who performed the procedure.

Lags Medical also used the in-house lab to run drug tests on patients’ urine samples. From 2017 through 2019, Lags Medical facilities often ordered the most extensive — and expensive — set of drug tests, which check for the presence of at least 22 drugs, according to state and federal data.

For perspective, in 2019, more than 23,000 of the most extensive drug tests were ordered on Medi-Cal patients under Lagattuta’s provider number, more than double the number tied to the next highest biller. The next five top billers were all lab companies.

Overall, from 2017 through 2019, nearly 60,000 of the most extensive drug tests were billed to Medicare and Medi-Cal under Lagattuta’s provider number. Medicare reimbursed Lagattuta $5.4 million for these tests during that period. Using state fee-for-service rates, the testing billed to Medi-Cal would have been worth an estimated $6.3 million. That doesn’t include less extensive drug screens or those billed under other providers’ numbers.

Pain management experts described the use of extensive screening as unnecessary in routine pain treatment; the overuse of such tests has been the subject of numerous Medicare investigations in recent years.

Private pain clinics like Lags Medical are only loosely regulated and generally are not required to hold a special license from the state. But the physicians who work there are regulated by the Medical Board of California.

In December 2019, a patient who’d visited clinics in both Visalia and the Central Coast filed a complaint against Lagattuta with the medical board claiming, among other things, that she received biopsies that were not properly performed, that she underwent excessive testing, and that positive drug tests had been falsified. The medical board had another pain management doctor review more than 300 pages of documents and found “no deviations from the standard of care” and “did not find any over testing, or improperly performed biopsies.”

He did, however, find some record-keeping problems, including numerous procedures in which patient consent was not documented. He also found instances in which procedures were performed and repeated without documentation that they were effective. The patient who filed the complaint was given a medial branch nerve block in November 2014, followed by a radiofrequency ablation in December, and another in February. No improvements for the patient were ever noted in the charts, the investigating doctor found.

The medical board chalked it up to a record-keeping error and fined Lagattuta $350.

Opioids Needed for ‘Halfway-Normal Life’

On a warm evening in late July, Leah Munoz drove her power wheelchair around the long plastic tables at the Veterans Memorial Building in Hanford, a dusty farm town in California’s Central Valley. Senior bingo night was crowded with gray-haired players waiting for the game to begin. She found an empty spot and carefully set out $50 worth of bingo cards, alongside her collection of 14 brightly colored daubers.

Munoz, 55 and a mother of six, said she has suffered from a litany of illnesses — thyroid cancer, breast cancer, lupus, osteoarthritis — that leave her in near-constant pain. She’s been playing bingo since she was a little girl, and said it helps distract from the pain and calm her mind. She looks forward to this event all week.

Munoz was a Lags Medical patient for about four years and, while her pain never disappeared, the opioids prescribed provided enough relief for her to continue doing the things she loved. “There’s a difference between addiction and dependence. I need it to live a halfway-normal life,” Munoz said.

leah and ramon munoz

After Lags Medical closed in May, her primary care doctor initially refused to refill her opioid prescriptions. She said she called the Lags Medical offices to try to get a copy of her medical records to prove her need, and even showed up in person. But she said she was unable to get them. As the pills dwindled and the pain surged, Munoz said, it became hard to leave her home. “I missed a lot of bingo, a lot of grocery shopping, a lot of going to my grandkids’ birthday parties. You miss out on life,” she said. Ultimately, she said, her primary care doctor referred her to another pain clinic, and she was able to resume her prescription.

Even with pain medications, Munoz said, she never received true relief during her time as a patient at Lags Medical. She said she felt coerced to get several injections, none of which seemed to help. “If I didn’t get the procedures, I didn’t get the pain medication,” she said. Her husband, Ramon, a landscaper who was also a patient, received an injection there that he said left him with permanent stiffness in his neck.

Munoz knows at least five other people at bingo night who were former patients at Lags Medical. One of them, Rick Freeman, came over to her table to chat. He swayed back and forth as he walked, his knees, he explained, swollen after 35 years living with HIV. At Lags Medical, Freeman said, he felt pressured by staff to receive injections if he wanted to continue receiving his opioid prescriptions. “If you don’t cooperate with them, they would reduce your meds down,” he said.

At the front of the room, Gail Soto, who ran the event, sold bingo cards to the latecomers. Soto, 72, said she injured her back while working an administrative job at a construction company years ago and suffers from spinal stenosis, rheumatoid arthritis, and fibromyalgia. She, too, was a patient at Lags Medical for years. In addition to her opioid prescription, Soto said, she received repeated injections and three nerve ablations. At first, the ablations helped, but what staff members didn’t tell her, she said, was that the nerves they destroyed could grow back. Ultimately, she said, the procedures left her in worse pain.

Soto’s biggest concern is the spinal stimulator that she said Lags Medical surgically inserted into her back five years ago. She said the doctors told her the device would work so well that she would no longer need her pain pills. She said they didn’t explain that the device would work only two hours a day, and on one side of her body. She remained in too much pain to give up her meds, she said, and, five years later, the battery is failing.

Soto sleeps in a recliner chair in her three-bedroom mobile home in Lemoore, another small city near Hanford. It’s well kept but humble, and she and her husband keep a collection of wind chimes on the front porch that create a wave of gentle music when a breeze passes by.

The couple take good care of each other and their two beloved Chihuahuas, but life has become increasingly difficult for Soto. As the battery on her spinal stimulator has started to fail, she said, she has sudden electrical pulses that shoot up her body.

GAIL SOTO

“My husband says sometimes when I sleep that my body will just jump up in the air,” she said. But now that Lags Medical is closed, she said, she can’t find a doctor willing to remove the device. “Most doctors are telling me right now, ‘We can’t, because we didn’t [put it in]. We don’t want nothing to do with that.’”

Waitlists and Withdrawal

Audrey Audelo Ramirez said she picked up her final refill from Lags Medical on June 4 and by July 4 had no meds left to treat her pain. Ramirez said she called every pain management clinic in Fresno, but none were taking new patients.

“They left us all high and dry,” she said. “Everybody.”

In the weeks that followed the closures, county officials throughout the Central Valley saw a flood of patients on high doses of opioids in search of new providers, they said. Patients couldn’t access their medical records, so other providers had no idea what their treatments had been.

“We had to create a crisis response to it because there was no organized response at that time,” said Dr. Rais Vohra, the interim health officer for Fresno County.

Fresno County’s health system is already lean, Vohra said. Toss in this abrupt closure and you end up in the kind of crisis rarely seen in other fields of medicine: “You’d never do this with a cancer clinic,” he said. “You’d never abruptly stop chemo.”

The state asked Dr. Phillip Coffin, director of substance abuse research for the San Francisco Department of Public Health, to run provider training and persuade doctors to take on new patients. Many practices have rules against taking new patients on opioids, or will refuse to prescribe doses above certain thresholds.

“We know that when you stop prescribing opioids, some people end up with death from suicide, overdose, increased illicit opioid use, pain exacerbations. It’s really important to have a continuity, and that is not really possible in the current opioid-prescribing culture,” Coffin said. The threat to patients is so severe that the FDA issued a warning in 2019 against cutting patients off from prescription opioids.

Gina, a retired nurse who asked to be identified by only her first name for fear she’d be discriminated against by other doctors, had been a Lags Medical patient for six years. She said she called every practice she could find in her Central Coast town, and was put on a waiting list at one. Suffering from a severe case of scoliosis, she started rationing the pain pills she had come to rely on.

When she finally secured an appointment, she said, she was told by the doctor she was on “some very strong meds” and he would fill only one of her two prescriptions. “You’re like a criminal,” she said. “You’re branded as ‘we don’t trust you.’”

She started experiencing withdrawal symptoms — sweating, lost appetite, sleeplessness, anxiety. Worst of all, her pain “came back with a vengeance,” she said.

“I think about this, what I’d have been like if I’d never gone through pain management. I sometimes wonder if I’d be better off.”

As for Ramirez, her primary care doctor finally secured an appointment for her at another pain clinic, she said. It was in the same space as the old Lags Medical clinic, and she said she recognized many of the staff members. But now there was a new name: Central California Pain Management. From her perspective, it was as if nothing had changed. And she still doesn’t know whether she needs to worry about the care she received during more than four years at Lags Medical.

This story was produced by Kaiser Health News. Senior correspondent Jordan Rau and Phillip Reese, an assistant professor of journalism at California State University-Sacramento, contributed to this report.

Gabapentinoids and Anti-Depressants Recommended for Diabetic Neuropathy

By Pat Anson, PNN Editor

People with painful diabetic neuropathy (PDN) should be treated with gabapentinoids, anti-depressants and sodium channel blockers, according to updated guidelines from the American Academy of Neurology (AAN). The guidelines also recommend some alternative treatments, such as ginkgo biloba, capsaicin patches and cognitive behavioral therapy, but strongly discourage the use of opioids.

The AAN’s new guidelines, published online in the journal Neurology, acknowledge that many of the recommended therapies for PDN don’t directly treat physical pain, but they improve mood and sleep, and that helps reduce “pain perception.”

“In treating patients with PDN, it is important to assess other factors that may also affect pain perception and quality of life. Patients with diabetes are more likely to have mood disorders (most commonly, major depression) and sleep disorders (especially obstructive sleep apnea) than the general population,” an AAN panel of experts found. “Therefore, treating concurrent mood and sleep disorders may help reduce pain and improve quality of life, apart from any direct treatment of the painful neuropathy.”

Nearly 26 million Americans have diabetes and about half have some form of neuropathy, according to the American Diabetes Association. PDN causes nerves to send out abnormal signals, causing patients to feel stinging or burning pain, as well as loss of feeling in their toes, feet, legs, hands and arms. More severe cases can result in ulcers or amputation of the affected limbs.

The last update to the AAN guideline was in 2011, when opioids such as morphine and oxycodone were said to be “probably effective and should be considered.” Much has changed over the last decade, and the AAN no longer supports their use for PDN.

"Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed," said lead author Brian Callaghan, MD, an associate professor of neurology at University of Michigan Health.

‘Probably’ Better Than Placebo

The only oral medications the AAN now recommends for PDN are gabapentinoids (pregabalin and gabapentin); serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine; tricyclic anti-depressants such as amitriptyline; and sodium channel blockers such as valproic acid, which are usually used to treat seizures. An SNRI can also be combined with a weak opioid like tramadol for PDN.

There are caveats to all of these drugs since the evidence for them is limited and they were originally developed for other conditions such as depression or epilepsy. For example, the guidelines state gabapentin is “probably more likely than placebo to improve pain” and pregabalin is “possibly more likely” to help with PDN.

Topical medications such as capsaicin and buprenorphine patches also get the lukewarm endorsement of “possibly” being better than a placebo.

When one class of medication doesn’t work for PDN, experts say patients should try another.

“Managing expectations is also important,” Callaghan said. “Our second recommendation urges the provider to be frank with patients that the goal is to reduce their pain. It may not be possible to completely resolve the symptoms.”

A 2017 study by the Agency for Healthcare Research and Quality found that duloxetine (Cymbalta) and some other anti-depressants are moderately effective at relieving PDN, but found little or no evidence that opioids and gabapentinoids are helpful in treating neuropathic pain.

Researchers say a significant limitation for all pain relievers – not just opioids – is that few studies examine their safety and efficacy longer than three months. PDN is a progressive disorder that is likely to last a lifetime.  

“Given the chronicity of pain in those with diabetic neuropathy and the potential for evolving side effects, long-term studies are needed to better inform the long-term pain management in this population. Specifically, future studies should focus on the long-term effects (positive and negative) of opioids in this population to determine whether there is any role for these medications in this population,” the AAN’s expert panel concluded.

Stem Cells Could Help Diabetics Produce Their Own Insulin

By Pat Anson, PNN Editor

With insulin prices soaring out-of-reach for many U.S. patients, there’s hope on the horizon for people with Type 1 diabetes. Researchers are making significant progress in developing stem cell therapies that could restore their ability to produce their own insulin.

Interim findings from two early stage clinical trials, published today in the journals Cell Stem Cell and Cell Reports Medicine, show that pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) began producing insulin in diabetic patients within months of being implanted in a tiny device under the skin.

While the amount of insulin secreted by the cells was not enough to cure Type 1 diabetes, they were sufficient enough to reduce the insulin requirements of some patients by as much as 20% and increase the amount of time spent in their targeted blood glucose range. Both studies showed that the stem cells can survive up to 59 weeks after implantation.

"A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes," says Eelco de Koning, MD, of Leiden University Medical Center in the Netherlands, who co-authored a commentary published in Cell Stem Cell. "Despite the absence of relevant clinical effects, this study will remain an important milestone for the field of human PSC-derived cell replacement therapies as it is one of the first to report cell survival and functionality one year after transplantation."

There are a number of caveats here. Less than three dozen patients participated in the Phase 1/2 studies, the outcomes were highly variable, and there were no control groups to compare the results with. The implanted stem cells were also derived from donors – meaning the patients had to take immunosuppressive drugs to prevent their bodies from rejecting the implants, leaving them vulnerable to infections. At least two patients experienced serious adverse events associated with having their immune systems suppressed.

Researchers still need to determine at what stage the stem cells are optimal for transplantation and the best place to implant them. It is also not clear how long the cells remain effective and whether the need for immunosuppressive therapy can be eliminated.

But the studies demonstrate that stem cells can mimic the insulin-producing pancreas cells that diabetics lack.

“A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes.”

— Eelco de Koning, MD

"The clinical road to wide implementation of stem cell-derived islet replacement therapy for type 1 diabetes is likely to be long and winding,” de Koning says. "But an era of clinical application of innovative stem-cell based islet replacement therapy for the treatment of diabetes has finally begun."    

About 460 million people worldwide have diabetes mellitus, a disorder in which the body does not produce enough insulin, causing blood sugar (glucose) levels to be abnormally high.  In Type 1 diabetes, the body’s immune system attacks the insulin producing cells of the pancreas. Left untreated, diabetes damages blood vessels and significantly raises the risk of stroke, heart attack and diabetic neuropathy.

Diet, exercise and regular insulin injections can help control Type 1 diabetes. But with insulin selling for about $300 a vial in the United States – 10 times more than in other developed countries --  some diabetics have rationed or even stopped taking the life-saving injections.

Another encouraging stem cell study -- involving just one patient -- was recently reported by Vertex Pharmaceuticals. A chronically ill man with Type 1 diabetes who has been taking insulin injections for decades – up to 34 units per day – began producing his own insulin after being injected with an experimental stem cell product called VX-880.

As a test, researchers only injected him with about half the targeted amount of VX-880, but within 90 days the man had reduced his need for insulin injections by 91 percent.

“These results from the first patient treated with VX-880 are unprecedented. What makes these results truly remarkable is that they were achieved with treatment at half the target dose,” Bastiano Sanna, PhD, Executive Vice President of Vertex, said in a statement. “While still early, these results support the continued progression of our VX-880 clinical studies, as well as future studies using our encapsulated islet cells, which hold the potential to be used without the need for immunosuppression.”

Vertex plans to expand the study to eventually include up to 17 patients, at multiple sites in the U.S. and Canada.

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.

Rare Disease Spotlight: Friedreich’s Ataxia

By Barby Ingle, PNN Columnist 

This month’s rare disease spotlight is on Friedreich’s ataxia, a genetic nervous system disorder, first described by Nikolaus Friedreich, a German doctor, in the 1860’s.

Dr. Friedreich may not have fully understood how genes worked over 150 years ago, but now we know that Friedreich’s ataxia is inherited by children who receive two defective copies of the FXN gene, one from each parent.

People born with Friedreich’s ataxia (FA) usually develop their first symptoms in childhood. They often have difficulty walking, poor balance and slurred speech due to nerve degeneration in their spinal cords. The symptoms are progressive and steadily worsen with time.

As we learned in high school biology class, the nervous system continually carries information from the brain to the body and back again to the brain. The nerves tell our bodies how to move and walk, without us having to think about every step. With FA these sensory signals are disrupted and the brain has difficulty coordinating balance and movement, resulting in impaired function. Fortunately, FA does not affect reasoning and thinking, just the ability to communicate.

There are other types of ataxia diseases, all rare, but FA is the most common hereditary ataxia condition in the United States. According to the National Organization for Rare Disorders, about 1 in every 50,000 people inherit this disorder.  

As I was researching this rare disease, I reached out to a teenager with FA to see how she was handling the symptoms at such a young age. To protect her identity, I will call her Ken.

It has been noted that it takes about 10 years of dedication in an area of study to become an expert on a topic. In Ken’s case, she has lived her whole life with FA and become an expert as her symptoms developed. Ken has difficulties with her balance, coordination and movement. She is on medication, but still has muscle spasms and soreness.

Ken also has anxiety and depression due to the disruptive effects of FA on her life. She believes there is a societal stigma on people with rare diseases and wishes the world wouldn’t judge her.  

About 15% of people with FA do not have any onset of symptoms until they are 25 or older. Some with FA can live well into their 60’s and beyond. Older patients with FA may develop scoliosis that requires surgical procedures or back braces.

Similar to other neurological conditions such as central pain syndrome, FA patients may develop difficulty swallowing. FA can also lead to cardiomyopathy, a disease of cardiac muscle that causes heart failure or arrhythmia. About a third of people with FA develop diabetes.

Genetic testing can now provide a conclusive FA diagnosis, so if an infant or toddler is showing symptoms of the disease, they should have an evaluation by a neurologist or another medical professional to determine the cause.  FA is not yet one of the genetic conditions covered by newborn screening legislation that I have spoken to my state representatives in Arizona about. But there are federal laws that help us check for inherited conditions like FA.

I look forward to the day that all 7,000+ rare diseases are screened for at the time of birth so that preventative care and coordination can take place, giving children a better chance at a fuller and longer life.  If you have Friedreich’s ataxia and are interested in being a part of the research to help find a cure and treatment, please contact the FA Research Alliance (FARA).

My hope for Ken and all those living with FA is that a cure will be found someday. In the meantime, we can do our part to help lower stigma about rare conditions by advocating for research and meaningful support for the millions of people who live with them.

Barby Ingle lives with reflex sympathetic dystrophy (RSD), migralepsy and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics. More information about Barby can be found at her website.

The Ever Changing Rules of CRPS

By Cynthia Toussaint, PNN Columnist

Two weeks ago, writhing at a level 10 pain, struggling to position my heating pad just right for a moment of relief, I told God that if it was time to take me, that was okay.

I thought I knew the rules of Complex Regional Pain Syndrome. After nearly four decades of trying to sidestep the burning torture, making every attempt to not poke the bear, I was confident I’d cracked the code enough to ward off any long-term flare. The kind that makes you think about dying.

But a shot of emotionally heightened experience, a jigger of COVID vaccine, and a splash of post-chemo recovery combined to turn the rules on their head. I think.

No question, I needed to see my mom. Due to my bout with aggressive breast cancer, a once-in-a-century pandemic, toxic family members and my mom’s advanced Alzheimer’s, I hadn’t seen her in a year and a half. When COVID loosened and I discovered she’d been placed in a nursing facility, a window of opportunity opened for a possible visit without seeing family members that harm and hurt.

The heavens opened and I got to spend a glorious day with an angel disguised as my mom.

But before that, wheeling up to the facility, my profound dread leapt to the nth degree, fearful that I might be facing a firing squad made up of familial cruelty. That, along with the emotional elation of time together with Mom – loving each other through her scattered cognition – sent waves of arousal through my nervous system, sparking over-the-moon pain as my partner, John, and I made our six-hour return trek to LA.

Over the next days, then weeks, as my pain maintained its grip, I knew in my gut this flare was something altogether new and terrible. But why? As I learned long COVID was inciting cytokine storms of pain and fatigue, and that many of my vaccinated sisters in pain were experiencing epic flares, I postulated that the vaccine (which had already re-erupted chemo side-effects) was probably the secret sauce for my exquisite agony. 

Without a doubt, this is the worst CRPS flare I’ve had in 35 years – and that one from the Reagan 80’s left me using a wheelchair to this day. Imagine my fear of what I might lose this go around. I’ll tell you, it’s soul-shaking.

In the past when I’ve experienced bad flares, my doctors have encouraged me to temporarily go up on gabapentin (Neurontin), a nerve medication I’ve taken for many years with good results. Because I despise taking drugs and never trust the “temporary” part, I’ve always resisted increasing the dose. That is, until now. Truth be told, a month into this flare, it took only a nudge from my doctor to increase my daily gabapentin in-take by 300mgs.

What a mistake. Fair to say, while the increase lowered my pain level by about three points, a HUGE improvement, the side effects were scorched-earth. I was wiped out to the point of being barely functional. This “never-a-napper” was falling asleep mid-day and I would wake with dementia-level disorientation. John had to remind me what day it was, where I lived, and what was happening in our lives.

I also suffered with suicidal ideation, compulsive thoughts, depression, joint pain, constipation, blurry vision and spatial difficulties. I’d traded one hell for another.

On the fourth night, I turned in bed and woke to the room (or was it my head?) spinning. The vertigo alerted me to the fact that if I continued this drug increase, I’d likely fall – and that could be catastrophic.

The next morning, with my doctor’s consent, I went off the extra gabapentin and, in its place, started Alpha Lipoic Acid. I took this supplement during chemo to ward off neuropathy, and it did the trick without side effects. Okay, to be fair, I wasn’t aware that it made my urine smell like burning tires as the chemo drugs masked that little nugget. Sorry, John.

That night, I experienced my worst pain ever, but, again, why? Even more confusing, I woke with honest-to-goodness relief, the last thing I expected. In fact, for the first time in weeks, I didn’t describe my morning swim as torture. As of this writing, the relief is holding, though threatening to return to the “I’m ready to die” level. But now, I have a taste of hope.

Still, I’m exhausted, scared and confused.

This is the essence of CRPS. It can come and go with little apparent cause. It can hide and seek, and its rules of engagement are ever shifting, ever evolving. It’s a devil that pokes its white-hot pitchfork of torture whenever, wherever it feels the urge. It’s crazy-making.

For all this madness, for all the uncertainty about my hell flare, these things I know for sure.

I did the right thing by getting the vaccine. COVID, or one of its variants, would (still might) kill me. I’m also doing my part to end this pandemic.

Chemo saved my life. While I’m betting it’s playing a hand in my current suffering, and will most likely present unknown damage down the line, I would not be alive without it.  

I was right to see my beautiful mother. I don’t know how much time either of us has, as I’m still a few years from “free-and-clear.” For my remaining days, I’ll always recall her reaction upon recognizing me, crying out my name and holding me so very tight. As my wonderful friend, Irene, reminds me, Mom and I have an epic love.  

Mom taught me to love myself, too. And I do. Completely. That love extends unconditionally to my CRPS, as it’s a part of me as much as anything is.

39 years into my dance with this mercurial disease, I doubt I’ll ever get ahead of it as its mystery and misery run too deep. Still, I can love it completely without complete understanding.

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 20 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.”

Pioneering Neurologist and CRPS Expert Remembered

By Pat Anson, PNN Editor

A pioneering neurologist who helped develop new treatments for Complex Regional Pain Syndrome (CRPS) has died. Robert Schwartzman, MD, passed away last week at the age of 81.

Dr. Schwartzman was an emeritus professor and former chair of the Department of Neurology at Drexel University College of Medicine in Philadelphia. He also taught and practiced medicine at Thomas Jefferson University, University of Texas Health Science Center, San Antonio and the University of Miami. He mentored hundreds of residents and colleagues, and authored several reference books on neurology.

The primary focus of Schwartzman practice and research was chronic pain, particularly CRPS (also known as Reflex Sympathetic Dystrophy or RSD), a chronic and severe pain syndrome affecting the nervous system.

At Jefferson University, Schwartzman founded the first CRPS clinic in the U.S. and pioneered the use of ketamine as a treatment for CRPS and other pain conditions.

“I met Dr Schwartzman in 2007 at a pain conference and joined the wait list to see him as my provider for RSD. I was finally able to so do in 2009. I shared what I learned with as many people as I could and continue to this day,” says PNN columnist Barby Ingle, founder and president of the International Pain Foundation. “His impact will live on through patients like me.”

DR. ROBERT SCHWARTZMAN

Ingle wrote about her first experience as a patient of Schwartzman in a PNN column. She went into the hospital in a wheelchair, but was able to walk out a week later after a series of ketamine infusions. She continues to get infusions regularly.

“He was a brilliant doctor and world expert on Reflex Sympathetic Dystrophy who's training and 40+ years of research help teach other providers who have also gone on to help millions of patients,” Ingle said in an email. “He will forever live in my heart as he is the provider who got me from my wheelchair and bed bound to walking and living life to my fullest. I will continue sharing his pioneering works and receiving his protocol for my infusion therapy. He is a treasure to our whole community.”   

“I didn't know him personally but I knew and respected his pioneering work,” says Lynn Webster, MD, past president of the American Academy of Pain Medicine. “He challenged our thoughts and understanding about how to treat the devastating disease of CRPS.  

“Dr. Schartzman took us into unexplored areas of how to treat a crippling disease. His work inspired me and countless others who have tried to implement his treatment approach for our own patients. He has given us a legacy of research that will be the foundation on which new discoveries about the mechanism and cure for CRPS will occur. The passing of Dr. Schwartzman is a huge loss for science and humanity.”

Schwartzman retired from clinical practice in 2013 and moved to Marco Island, Florida. Funeral arrangements are private. His family requests that any donations in his memory be made to any Florida wildlife or conservation charity.

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 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.

My Cancer Is Back: Facing Surgery With CRPS

By Cynthia Toussaint, PNN Columnist

After hearing the worst words of my life, “Your cancer has grown back,” I felt hopeless and hated the world. Worse, I had to tell my longtime partner and caregiver, John, the grim news. How could we pull up our frayed boot straps again and survive yet another impossible health crisis?

Since getting Complex Regional Pain Syndrome (CRPS) four decades ago, people often use words like “fighter,” “pain warrior” and “super human” to describe me. The most recent catch phrase is, “Cynth, you got this!”

I’ve come to detest this perceived awesomeness. I don’t want to be an uber-person. I never did. I’m tired. I’m so, so tired. And I long for a slice of vanilla-flavored normal.

As the owner of CRPS and 19 comorbidities, I could not afford the diagnosis of triple negative breast cancer, the most aggressive form. But that’s what was delivered, since luck has never been this lady’s lot.

Without consulting me, the universe long ago decided that I’m supposed to slay every dragon while surviving never ending illness and trauma. This latest hell-news has filled me with anger, rage and major depression.

So much so, that for the first time ever, I’m isolating. This social butterfly has returned to her cocoon, unable to feel joy.

I can’t sleep as I’m plagued by night terrors. Each afternoon, my body trembles uncontrollably. Once heavenly activities, like meditation, exercising and eating, are now chores.

John massages my taut muscle tension through the days and nights – and my IBS has gone haywire. My bubbly spirit is absent and what’s left is demoralized.

And not so long ago, I thought I had this thing licked.

Early last year, after six months of weighing my impossible-with-CRPS treatment options, I started aggressive chemotherapy knowing that this regimen could leave me with a life not worth living. The dream was that my pain would stay in check and I’d achieve a Clinical Complete Response (cancer that cannot be seen with imaging). I’m certain chemotherapy almost ended me, as I was left with virtually no immune system. As a bonus, this was during COVID. 

I was coined a “super responder” when I miraculously accomplished a complete response. At that point, the odds were strongly in my favor that the cancer was gone. But the only way to be sure was to do the follow-up standard of care surgery, which I chose to forego because, with CRPS, surgery is, well, not an option.

The doctors were floored by how well I did, and every indicator leaned toward a clean pathology report. I was ready to move on with my life, one that I felt I’d earned by doing everything right (diet, exercise, stress management, good sleep – the whole kit and caboodle!) One doctor commented, “Don’t even look at the survival numbers. They don’t apply to you anymore.”   

True to form, things went as far south as possible. Because I’m one of the unlucky ones who’s cancer stem cells never went away, my malignancy is growing back. This is not a “recurrence,” but a “persistence” because the chemo didn’t hold.

And now that my complete response is gone, I’ll never have my prior odds. John has lamented for years, “You NEVER get a break!” and I’m finally seeing it his way.

For a chance of survival, I must now have – ta daaa!! – surgery. The doctors tell me my best shot is to do a lumpectomy with follow-up radiation or a stand-alone mastectomy.

Tragically, radiation is off the table as it often causes neuropathic pain. In fact, a radiologist who I respect told me flat out, “I can’t ethically do it to you.” And during a recent visit with my surgeon, she strongly advised that, due to CRPS, I’m not a candidate for a mastectomy, let alone reconstructive surgery. Wow.

Finding a New Care Team

Adding insult to injury, out of nowhere, my lead oncologist dropped me! She did so due to questionable guidance (something I can’t detail here) and is fearful of litigation, which doesn’t make it hurt less. This woman had become my hero and I trusted her with my heart and life. Her betrayal has been soul-crushing and created a crisis of faith. I don’t know who or what to believe in anymore.

But through the shadows, I’m quietly planning my next move – and will take on Round Two one slow... step… at… a... time. I’m assembling a new-and-improved care team to up my odds, including an oncologist, acupuncturist, physical therapist, pain specialist and psychologist. I’ve sweetened the pot with an EMDR (an effective technique for trauma release) practitioner who specializes in people with CRPS. Heck, I’ve even lined up the use of a heated pool in these COVID shutdown days.    

I’m going to have a lumpectomy, a word I can still barely say, let alone write. The scariest part is that my surgeon will also remove a possibly involved lymph node in a nerve rich area, ripe for ample, new pain. My new oncologist is concerned that due to a surgery-induced CRPS flare, my arm may freeze up and become a non-functional torture machine.

Even if the surgery mercifully works without condemning me back to bed, this wouldn’t flip me a “get-out-of-jail-free” card. Because I can only do the “minor” surgery without radiation, my odds of a quick recurrence remain high. This means I’ll be on the prowl for some off-the-grid insurance, perhaps low-dose chemo or an immunotherapy clinical trial. But neither can measure up to the standard of care radiation.

God, to be well enough to be sick!         

So, here I am again, looking down the barrel of a gun, knowing it likely has a bullet with my name on it. Like I said, I’m tired and angry. I’m up to my ass with picking the lesser of two evils, and having to crack the code of the near impossible.

Give me a break, already! And I don’t mean this in a small way. I’m shouting out to the big, bad, ice cold universe that I hope, somewhere, somehow, has a heart.

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.” 

New European Guideline Says Opioids ‘Do Not Work’ for Many Types of Chronic Pain

By Pat Anson, PNN Editor

Calling opioid medication a “two edged sword,” the European Pain Federation (EFIC) has released new guidelines that strongly recommend against using opioids to treat fibromyalgia, low back pain, migraine, irritable bowel syndrome and other types of chronic non-cancer pain.

“The new recommendations advise that opioids should not be prescribed for people with chronic primary pain as they do not work for these patients,” the EFIC said in a statement.

However, the guideline states that low doses of opioids may be suitable for treating “secondary pain syndromes” caused by surgery, trauma, disease or nerve damage, but only after exercise, meditation and other non-pharmacological therapies are tried first.

“Opioids should neither be embraced as a cure‐all nor shunned as universally dangerous and inappropriate for chronic noncancer pain. They should only be used for some selected chronic noncancer pain syndromes if established non‐pharmacological and pharmacological treatment options have failed,” the guideline states. “In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients.”

Opioid pain relievers are not as widely used in Europe as they are in the United States or Canada. The EFIC said it was trying to “allay concerns over an opioid crisis” developing in Europe, as it has in North America.       

“As the leading pain science organisation in Europe, it is crucial that EFIC sets the agenda on issues such as opioids, where there are growing societal concerns. These recommendations clarify what role opioids should play in chronic pain management,” EFIC President Brona Fullen said in a statement.

The guideline’s lead author, Professor Winfried Häuser, said he and his colleagues tried to strike a middle ground on the use of opioids.

“The debate on opioid-prescribing for chronic non-cancer pain has become polarized: opioids are either seen as a dangerous risk for all patients, leading to addiction and deaths, or they are promoted as most potent pain killers for any type of pain,” said Häuser, who is an internal medicine specialist in Germany.

“Opioids are still important in the management of chronic non-cancer pain – but only in some selected chronic pain syndromes and only if established non-pharmacological and non-opioids analgesics have failed or are not tolerated.”

PROP Consulted for European Guideline

The guideline was developed by a 17-member task force composed of European experts in pain management, including 9 delegates selected by EFIC’s board “who advocate and who are critical with the use of opioids.” Only one delegate from Pain Alliance Europe represented patients.

The recommendations developed by the task force were reviewed by five outside experts, including Drs. Jane Ballantyne and Mark Sullivan, who belong to Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group in the U.S.  Ballantyne is PROP’s President, while Sullivan is a PROP board member. Several changes suggested by the outside experts were adopted.

Coincidentally, Ballantyne, Sullivan and three other PROP board members were involved in the drafting of the opioid guideline released in 2016 by the U.S. Centers for Disease Control and Prevention. That controversial guideline is now being rewritten by the CDC after voluminous complaints from patients and doctors that the recommendations led to forced tapering, withdrawal, uncontrolled pain and suicides.

Sullivan and two other PROP board members were also involved in drafting Canada’s 2017 opioid guideline, which was modeled after the CDC’s and provoked similar complaints from Canadian pain patients.

90 MME Recommended Limit

The CDC and Canadian opioid guidelines appear to have been used as resources by the EFIC task force, which adopted many of the same recommendations, even while acknowledging the low quality of evidence used to support them.   

One recommendation is straight out of the CDC guideline, advising European doctors to “start low and go slow.” Prescribers are urged to start patients on low doses of 50 morphine milligram equivalents (MME) or less a day and to avoid increasing the dosage above 90 MME/day.

One significant difference with the North American guidelines is that the EFIC recommends that opioids not be prescribed for fibromyalgia, migraines and other chronic “primary pain” conditions for which there is no known cause – suggesting those disorders have an emotional or psychological element that will lead to opioid abuse.

“Prescription of high doses of opioids to patients with primary pain syndromes might have been a factor driving the opioid crisis in North America,” the EFIC guideline warns.

“This was further compounded by patient characteristics that included physical and psychological trauma, social disadvantage and hopelessness that served as a trigger for reports of pain intensity prompting prescriptions of more opioids.”

Secondary pain conditions for which opioids “can be considered“ include multiple sclerosis, stroke, restless leg syndrome, Parkinson’s disease, rheumatoid arthritis, phantom limb pain, non-diabetic neuropathy, spinal cord injuries and Complex Regional Pain Syndrome (CRPS). 

Unlike the North American guidelines, the EFIC acknowledges that there are physical and genetic differences between patients. Some patients who are rapid metabolizers “might require higher dosages of opioids than the ones recommended by the guidelines.“

EFIC GRAPHIC

The EFIC also warns that its guideline should not be used to justify abruptly tapering or discontinuing opioids for anyone already prescribed at higher dosages. The recommendations are also not intended for the management of short-term acute pain, sickle cell disease or end-of-life care.

Insurance Claims Show Lyme Disease More Widespread

By Pat Anson, PNN Editor

A new analysis of insurance claims by the Centers for Disease Control and Prevention suggests that Lyme disease may be far more widespread in the United States than current estimates.

CDC researchers looked at data from MarketScan, a large commercial insurance claims database, and found that Lyme disease diagnoses from 2010 to 2018 were six to eight times higher than the number of cases reported to a federal disease surveillance program.

Lyme disease is a bacterial illness spread by ticks. When left untreated, it can lead to chronic disorders such as fatigue, muscle and joint pain, cognitive issues and other symptoms that are often diagnosed as fibromyalgia, neuropathy and autoimmune disorders.

Most reported cases of Lyme disease occur in 14 states in the Northeast, mid-Atlantic and upper Midwest, especially during the summer months when more people spend time outdoors. Recent studies show Lyme is spreading to neighboring states and is no longer just a seasonal disease, possibly do to the effects of climate change.

The CDC analysis of insurance claims filed by nearly 23 million Americans identified over 140,000 people who were diagnosed with Lyme disease during the study period. That works out to a nationwide rate of 73 cases for every 100,000 people, a rate substantially higher than the 9 cases per 100,000 reported by the surveillance program.

“Age and sex distributions among Lyme disease diagnoses in MarketScan were similar to those of cases reported through surveillance, but proportionally more diagnoses occurred outside of peak summer months, among female enrollees, and outside high-incidence states,” wrote lead author Amy Schwartz, an epidemiologist in the CDC’s Bacterial Diseases Branch.

Schwartz and her colleagues say the larger number of Lyme cases reported by MarketScan may be the result of misdiagnoses, but the volume of claims warrant further investigation.

“Although Lyme disease diagnoses identified from claims data are not supported by the robust evidence of infection required for surveillance reporting, they are a consistent indicator of trends in the healthcare system. In addition, the sheer volume of data available through MarketScan provides potential for new insights into the epidemiology of Lyme disease diagnoses in the United States,” they said.

The CDC findings are similar to a 2017 analysis of insurance claims by the non-profit FAIR Health, which found an unexpected surge in Lyme disease cases during the winter and early spring.

Early symptoms of Lyme disease include fever, chills, headache, fatigue, muscle and joint aches, and swollen lymph nodes. A delayed rash often appears at the site of the tick bite. The rash grows in size and sometimes resembles a bulls-eye. Lyme disease is usually treated with antibiotics.

About 30,000 cases of Lyme disease are reported annually by state and local health departments to the surveillance program. The CDC acknowledges, however, that the actual number of cases is probably much higher and that about 300,000 Americans may become infected every year.