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.”  

Tiny Electrode Could Expand Use of Spinal Cord Stimulators

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Follow Treatment Guidelines for Low Back Pain and Get Back to Work Sooner

By Pat Anson, PNN Editor

Employees with acute low back pain miss fewer days of work if they exercise, take over-the-counter pain relievers and are not prescribed opioid medication, according to a large new study of worker compensation claims in California.

"The closer people's care follows evidence-based guidelines, the faster their back pain resolves, by quite a bit," said Kurt Hegmann, MD, director of the University of Utah Rocky Mountain Center for Occupational and Environmental Health.

Hegmann and his colleagues analyzed insurance data for nearly 60,000 people with low back pain from 2009 to 2018, comparing their treatment to guidelines created by the American College of Occupational and Environmental Medicine. Those guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants and physical therapy for low back pain, while frowning on the use of opioids or invasive procedures such as spinal injections.

The research findings, recently published in PLOS ONE, showed that people who didn’t follow treatment guidelines missed an average of 11 more days of work each year compared to those who only had recommended treatments.

Opioids were once commonly prescribed for low back pain, a practice that has fallen out of favor due to fears of addiction and overdose. In the nine years of the study, researchers found that opioid prescribing for low back pain declined by 86 percent, fueled in part by insurers who were unwilling to pay for the drugs.

"The reduction in opioids prescription is particularly impressive," Hegmann said. "In this case, the insurer is likely to not pay for opioids even if they are prescribed. It suggests what's possible when the 'carrot' of good health care is missed and instead the 'stick' of compliance with a guideline is in place."

Nearly two-thirds of the people included in the study received at least one non-recommended treatment, although adherence to treatment guidelines improved over time. In 2009, 10% were treated according to guidelines, but that rose to 18% by 2018.

Low back pain is the world’s leading cause of disability. It mostly affects adults of working age in lower socioeconomic groups, who often have physically demanding jobs.

Treatment guidelines for low back pain have changed considerably in the last 20 years. At one time, bed rest was commonly recommended, a treatment now seen as counterproductive. Moderate exercise and physical activity help people return to work sooner.

"Being out of work impacts many facets of your life," said first author Fraser Gaspar, PhD. "In addition to the physical disability that's causing the person to miss work, the worker is making less money, while they often incur additional costs and experience mental strain. Getting people back to their normal lives is really important, and our research shows that following guidelines makes that happen faster."

Medical Device Makers Paid Billions to Doctors To Use Their Products

By Fred Schulte and Elizabeth Lucas, Kaiser Health News

Dr. Kingsley R. Chin was little more than a decade out of Harvard Medical School when sales of his spine surgical implants took off.

Chin has patented more than 40 pieces of such hardware, including doughnut-shaped plastic cages, titanium screws and other products used to repair spines — generating $100 million for his company SpineFrontier, according to government officials.

Yet SpineFrontier’s success arose not from the quality of its goods, these officials say, but because it paid kickbacks to surgeons who agreed to implant the highly profitable devices in hundreds of patients.

In March 2020, the Department of Justice accused Chin and SpineFrontier of illegally funneling more than $8 million to nearly three dozen spine surgeons through “sham consulting fees” that paid them handsomely for doing little or no work. Chin had no comment on the civil suit, one of more than a dozen he has faced as a spine surgeon and businessman. Chin and SpineFrontier have yet to file a response in court.

Medical industry payments to orthopedists and neurosurgeons who operate on the spine have risen sharply, despite government accusations that some of these transactions may violate federal anti-kickback laws, drive up health care spending and put patients at risk of serious harm, a KHN investigation has found.

These payments come in various forms, from royalties for helping to design implants to speakers’ fees for promoting devices at medical meetings to stock holdings in exchange for consulting work, according to government data.

Health policy experts and regulators have focused for decades on pharmaceutical companies’ payments to doctors — which research has shown can influence which drugs they prescribe. But far less is known about the impact of similar payments from device companies to surgeons. A drug can readily be stopped if deemed harmful, while surgical devices are permanently implanted in the body and often replace native bone that has been removed.

‘Staggering’ Amounts of Money

Every year, a torrent of cash and other compensation flows to these surgeons from manufacturers of hardware for spinal implants, artificial knees and hip joints — totaling more than $3.1 billion from August 2013 through the end of 2019, a KHN analysis of government data found. These bone specialists make up a quarter of U.S. doctors who have accepted at least $100,000 or more, and two-thirds of those who raked in $1 million or more, from the medical device and drug industries last year, the data shows.

“It is simply so much money that it is staggering,” said Dr. Eugene Carragee, a professor of orthopedic surgery at the Stanford University Medical Center and critic of the medical device industry’s influence. Much of the money is deemed to be compensation for consulting duties or medical research, or royalties for inventing, or fine-tuning, new surgical tools and techniques. In some cases, it pays for trips or splashy junkets or rewards surgeons for promoting products to their peers.

Device makers say the long-established practice leads to higher-quality, safer products. “Doctors help develop and refine medical devices, and they even create new devices themselves, sharing their intellectual property with companies to help save and improve patients’ lives,” said Scott Whitaker, president and CEO of AdvaMed, the medical technology industry’s trade group.

But industry whistleblowers and government investigators say all that money changing hands can corrupt medical judgment and tempt surgeons to perform unnecessary and wasteful operations. In ongoing lawsuits, patients say they have suffered life-altering injuries from screws or other spinal hardware that snapped apart or live with disabilities they blame on defective knee or hip implants.

Patients alleging injuries range from seniors on Medicare to celebrities such as Olympic gold medalist Mary Lou Retton, who had surgery to replace both her hips. The gymnast sued device maker Biomet in January 2018, alleging the hip implants were defective. The suit has since been settled under confidential terms.

The case of Chin’s company, SpineFrontier, is among more than 100 federal fraud and whistleblower actions, filed or settled mostly in the past decade, that accuse implant surgeons of taking illegal compensation from device makers — from surgeon entrepreneurs like Chin to marquee names like Medtronic and Johnson & Johnson. In some cases, device makers have paid hundreds of millions of dollars in fines to wrangle out of trouble for their involvement, often without admitting any wrongdoing.

Court pleadings examined by KHN identified more than 700 surgeons who have taken money, including dozens who pocketed millions in royalties, fees or other compensation from 2013 through 2019. The names of hundreds more surgeons were redacted in court filings or sealed by judges.

Court filings named 35 spine surgeons who used SpineFrontier’s surgical gear, some for years. At least six of those surgeons have admitted wrongdoing and paid a total of $3.3 million in penalties. Another has pleaded guilty to criminal charges. It’s illegal under federal law to accept anything of value from a device maker for using its wares, though most offenders don’t face criminal prosecution.

Chin, 57, who lives in Fort Lauderdale, Florida, and owns SpineFrontier through his investment company, declined comment about the DOJ lawsuit or the consulting agreements.

“There is a court date [for the DOJ case] as ordered by a judge,” Chin said via email. “If we get to that point the facts of the case will be litigated.”

Back Surgeries Under Scrutiny

The nation’s outlay for spine surgery to treat back pain, or to replace worn-out knees and hips, tops $20 billion a year, according to one industry report. Taxpayers shoulder much of that cost through Medicare, the federal program for those 65 and older, and Medicaid, which caters to low-income people.

In one common spinal procedure, surgeons may replace damaged discs with an implant and screws and metal rods that hold it in place. The demand for surgery to replace worn-out knees and hips also has mushroomed as aging boomers and others seek relief from joint pain that restricts their movement.

Perhaps not surprisingly, the competition for sales of orthopedic devices is fierce: Some 250 companies proffer a dizzying array of products. Industry critics blame the Food and Drug Administration, which allows manufacturers to roll out new hardware that is substantially equivalent to what already is sold — though it often is marketed as more durable, or otherwise better for patients.

“The money is just phenomenal for this medical hardware,” said Dr. James Rickert, a spine surgeon and head of the Society for Patient Centered Orthopedics, an advocacy group. He said most of the products are “essentially the same,” adding: “These are not technical instruments; [it’s often] just a screw.”

Hospitals can end up charging patients $20,000 or more for the materials, though they pay much less for them. Spine surgeons — who make upward of $500,000 a year — bill separately and may charge $8,000 to $20,000 for major procedures.

Which equipment hospitals choose may fall to the preference of surgeons, who are wooed by manufacturing sales reps possibly present in the operating room.

And it doesn’t stop there. Whistleblower cases filed under the federal False Claims Act allege a startling array of schemes to influence surgeons, including compensating them for joining a medical society created and financed by a device company. In other cases, companies bought billboard space or other advertising to promote medical practitioners, hired surgeons’ relatives, paid for hunting trips — even mailed checks to their homes.

Orthopedic and neurosurgeons collected more than half a billion dollars in industry consulting fees from 2013 through 2019, federal payment records show.

These gigs are legal so long as they involve professional work done at fair market value. But they have drawn fire as far back as 2007, when four manufacturers that dominated the hip and knee implant market, including a J&J division, agreed to pay $311 million to settle charges of violating anti-kickback laws through their consulting deals.

KHN found at least 20 whistleblower suits, some settled, others pending, that have since accused device makers of camouflaging kickbacks as consulting work, including paying doctors to sit on suspect “advisory boards” or other activities that entailed little work to justify the fees.

In November 2019, device maker Life Spine and two of its executives admitted to paying consulting fees to induce dozens of surgeons to use Life Spine’s implants in the operating room. In all, 21 of the top 30 Life Spine adopters were paid and they accounted for about half its total device sales, according to the Justice Department. Life Spine and the executives paid a total of $6 million in penalties. The company did not respond to requests for comment.

Similarly, SpineFrontier received “the vast majority” of its sales, more than $100 million worth, from surgeons who were compensated, the Justice Department alleges. Often, they were paid by way of a “sham” company run by Chin’s wife, Vanessa, from a mail drop in Fort Lauderdale, according to the Justice Department. Vanessa Dudley Chin, a defendant in the DOJ civil case, had no comment.

Kingsley Chin told KHN via email that he takes no salary from SpineFrontier, based in Malden, Massachusetts. In 2013, Chin received $4.3 million in income from the company, according to court filings in a divorce case in Philadelphia from an earlier marriage. In 2018, SpineFrontier valued Chin’s interest in the company at $75 million, according to government records, though its current worth is unclear.

SpineFrontier’s management thought paying doctors was “the only reliable way to steadily increase its market share and stave off competition,” Charles Birchall, a former business associate of Chin’s, alleged in a whistleblower complaint. The case is one of two whistleblower suits filed against SpineFrontier that the DOJ has joined and consolidated. Chin has yet to file a response in court.

From March 2013 through December 2018, the company offered some surgeons $500 or more an hour for “consulting,” which could include the time they spent operating on patients — even though they already were being paid by Medicare or other health insurers. Other surgeons were paid repeatedly to “evaluate” the same products, though their feedback was “often minimal or nonexistent,” according to the DOJ complaint.

Patient Injuries Pile Up

While the payments have piled up for doctors, so have injuries for patients, according to lawsuits against device makers and whistleblower testimony.

Orthopedic surgeon-turned-whistleblower Dr. Manuel Fuentes is suing his former employer, Florida device maker Exactech, alleging it offered “phony” consulting deals to surgeons who had complained about alarming defects in one of its knee implants.

Their findings should have been forwarded to the FDA to protect the public, Fuentes and two former Exactech sales reps alleged in their suit. Instead, the company paid the surgeons “to retain their business and secure their silence” about patients needlessly undergoing a second operation to address the defects implanted in the first, according to the suit. Lawyer Thomas Beimers, who represents Exactech in the case, said the company “emphatically denies the allegations and looks forward to presenting the real facts to the court.” In a court filing, the company said the suit was “full of conclusory, vague and immaterial facts” and said it should be dismissed.

In Maryland, spine surgeon Dr. Randy F. Davis faces a lawsuit filed in early 2020 by 14 former patients who claim he implanted counterfeit hardware from a device distributor that had paid him hundreds of thousands of dollars in consulting fees and other compensation.

Davis used the hardware, which had not been FDA-approved, on about 250 patients at the University of Maryland Baltimore Washington Medical Center in Glen Burnie, Maryland, according to the suit. Several patients say screws or other implants failed and they sustained permanent injuries as a result. One woman said she was left with little feeling in her right foot and needs a cane or walker to get around. Others claim “extreme mental anguish” for fear the hardware inside them will fail, according to the suit.

The patients allege that Davis improperly disposed of defective screws and other hardware he removed rather than send the items for analysis or report the failures to authorities. Instead, the University of Maryland hospital sent “hush” letters to patients that falsely told them that no defects had been found, according to the suit. A spokesperson for the hospital, which also is a defendant in the suit, denied the allegations, noting: “We will vigorously defend this lawsuit and at its conclusion are quite confident we will prevail.” Davis and his lawyer didn’t respond to repeated requests for comment. The lawsuit is pending in Anne Arundel County state court.

Surgeons are free to implant devices they helped bring to market or promoted, though doing so can prompt criticism when injuries or defects occur.

That happened when three patients filed lawsuits in 2018 against Arthrex, a Florida device company. The patients argued they were forced to undergo repeat operations to replace defective Arthrex knee devices implanted by Pennsylvania orthopedic surgeon Dr. Thomas Meade.

Meade was not a defendant in the cases. But the patients accused him of misleading them about the product’s safety and a recall. One noted that Meade had served as a prominent consultant to Arthrex and had “participated in the design, testing, marketing, promotion and sales” of the knee implant. The patient alleged that Arthrex had paid Meade more than $250,000 for work that included “promotional speaking, travel, lodging, and consulting.”

In court filings, Arthrex admitted making payments to Meade for “consulting and royalties” but denied wrongdoing. The cases were settled in 2020. Meade did not respond to requests for comment.

Chin’s dual roles as SpineFrontier’s CEO and user of its hardware was called a “huge” conflict of interest by a judge in a pending malpractice case filed against him and the company in South Florida.

In that case, Miami resident Patrick Chapoteau alleges Chin performed back surgery in 2014 using SpineFrontier hardware even though it had little chance of success. According to the suit, a Chin-designed screw implanted to stabilize Chapoteau’s spine broke in half, causing him pain and disabling injuries.

In a legal brief, Chin’s lawyers argued that he regularly operates on people with disabling back problems, noting: “The surgery is sophisticated and challenging. On a few rare occasions, his patients have not obtained the relief they expected or experienced unanticipated complications that required additional care.”

Joseph Wooten, a former Chin patient and Florida power company employee, alleged in a 2014 lawsuit in Broward County Circuit Court that Chin had 15 previous malpractice claims that had ended in more than $8 million in settlements, an assertion Chin’s lawyers disputed.

“He never told me of his bad record injuring people,” Wooten, 64, wrote in a court filing. He and his wife, Kim, said the surgery caused “debilitating and life-altering injuries.” The case has since been settled. Chin acknowledged no wrongdoing and the terms are confidential.

KHN reviewed court pleadings in nine settled malpractice cases in Philadelphia, where Chin served on the faculty of the University of Pennsylvania Medical School from 2003 to 2007, and six in South Florida filed since 2012. Details of the settlements are confidential. Five of the six South Florida cases are pending, including one filed in December by the widow of a man who died shortly after spine surgery. In all the cases and settlements, Chin has denied negligence.

In her lawsuit pending against Chin in South Florida, Nancy Lazo of Hialeah Gardens, Florida, said she slipped and tumbled down the stairs outside her Miami office, landing on her back and arm. When the pain would not go away, she turned to Chin and had two operations, in 2014 and 2015. Her lawyers allege that a SpineFrontier screw Chin implanted in her spine in the second procedure caused nerve damage. Lazo, 51, a former billing clerk with two adult sons, said she can no longer work and remains in “constant” pain. “Based on what my doctors have told me,” she said, “I will never get back to normal.” Chin denied any negligence and the case is pending.

Government Struggles to Keep Pace

Concerns that industry payments can corrupt medical practice have been aired repeatedly at congressional hearings, in media exposés and in federal investigations. The recurring scandals led Congress to require that device makers and pharmaceutical companies report the payments, starting in August 2013, to a government-run website called Open Payments. That website shows that payments to all doctors have risen from $8.6 billion in 2014 to just over $10 billion last year. A recent study found payments by device makers exceeded those of pharmaceutical companies by a wide margin.

Both the North American Spine Society and the American Academy of Orthopaedic Surgeons told KHN that close ties with the industry, while seeming to generate huge payouts to some surgeons, lead to the design of safer and better implants.

“These interactions are really essential for good outcomes in patient care and that needs to be preserved,” said Dr. Joshua J. Jacobs, who chairs the orthopedic surgery department at Rush University Medical Center in Chicago and the AAOS’ ethics committee.

Although more than 600,000 American doctors lap up industry largesse, most do so through small payments that cover the cost of food, drinks and travel to industry-sponsored events. When it comes to big money, however, orthopedists and neurosurgeons dominate, collecting 25% of the total — even though they represent only 5% of the doctors accepting payments, according to the KHN analysis of Open Payments data.

Dr. Charles Rosen, a spine surgeon and co-founder of the advocacy group Association for Medical Ethics, said he was once offered $2,000 just to show up and watch an industry-sponsored panel. “It was quite unbelievable,” he said.

Rosen said while he believes a “relatively small number” of surgeons cash whopping industry checks, many who do so are influential figures who can “help direct medical care.”

Government data confirms that even as several orthopedic and neurosurgeons received tens of millions of dollars in 2019, 81% of them got less than $5,000 from industry.

Federal officials recently signaled their displeasure with the hefty fees paid to doctors who promote their products to peers, especially at restaurants, entertainment or sports venues that feature free food and booze but little educational content. In November, the inspector general at the Department of Health and Human Services issued a special fraud alert that such gestures could violate anti-kickback laws.

Companies that ignore the reporting law can be fined up to $1 million, though no fines were levied from 2014 through spring 2020, according to a CMS report. That changed in October, when device giant Medtronic agreed to pay the government $9.2 million to settle allegations that it paid kickbacks to Sioux Falls, South Dakota, neurosurgeon Dr. Wilson Asfora to promote its goods.

Officials said the company sponsored more than 100 events at a Brazilian restaurant owned by the surgeon to clinch the sales. Just over $1 million of the fine was assessed for failing to report the transactions. A Medtronic spokesperson said the company fired or took other disciplinary action against the sales employees involved and “remains committed to maintaining the highest standards of ethical conduct.”

KHN identified four spinal device makers — including SpineFrontier — that have been accused in whistleblower cases of scheming to hide consulting payments from the government.

Responding to written questions, a CMS spokesperson said the agency “has multiple formal compliance actions pending which it is unable to discuss further at this time.”

But penalties for paying, or accepting, kickbacks often are small compared with the profits they can generate.

“Some people would say if you penalize companies enough, they won’t be making these offers,” said Genevieve Kanter, an assistant professor at the University of Pennsylvania Perelman School of Medicine. She said small fines may be chalked up to the “cost of doing business.”

The Federation of State Medical Boards does not keep data on how often its members discipline doctors for civil kickback offenses, according to spokesperson Joe Knickrehm. The federation has “long advocated for stronger reporting requirements,” Knickrehm said.

Justice Department officials would not discuss whether they are seeking fines from more surgeons. But in a statement in April 2020, then-U.S. Attorney for the District of Massachusetts Andrew E. Lelling noted that the government will investigate any doctor “who accepts money from a device manufacturer simply for using that company’s products.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Pain Patients Worried About CDC Expanding Opioid Guideline

By Pat Anson, PNN Editor

 “These guidelines have been a disaster for people with chronic pain.” 

“The guideline is flat out wrong on facts, wrong on science and wrong on medical ethics.” 

“The CDC has no qualifications or authority to develop pain management guidelines, especially those pertaining to opioid therapy.” 

Those are just a few of the comments we received from nearly 4,200 pain patients and healthcare providers who participated in PNN’s survey on impending changes to the CDC's opioid prescribing guideline. 

“It has been misunderstood, misapplied, bastardized and weaponized to use against chronic pain patients,” is how one pain sufferer put it.  

People obviously have strong opinions about the CDC guideline. Can it be changed and made more effective? Or should the entire guideline be thrown out? 

Nearly 75% of the people we surveyed believe the guideline should be withdrawn or revoked. That’s not likely to happen, however, as the CDC completes a lengthy review and update of the guideline that started two years ago.

If anything, the agency seems intent on expanding the guideline to include specific recommendations for treating short-term acute pain, migraine and possibly other pain conditions such as fibromyalgia. 

That’s the route recently taken by two advisory panels in Europe, which released guidelines that are even stricter on the use of opioids than the CDC’s.

WHAT SHOULD BE DONE WITH CDC OPIOID GUIDELINE?

This month the UK’s National Institute for Health and Care Excellence advised doctors not to prescribe opioids or any other pain reliever for fibromyalgia, chronic headache, musculoskeletal pain and other types of “primary chronic pain” for which there is no known cause.

In March, the European Pain Federation (EFIC) released similar guidelines, saying “opioids should not be prescribed for people with chronic primary pain as they do not work for these patients.”

At least two members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group, served as consultants to the EFIC in making its recommendation. PROP has long urged the CDC to make a similar statement in its guideline.

“This recommendation should explicitly state that opioids should be avoided for fibromyalgia, chronic headache and chronic low back pain,” PROP’s board wrote in a 2015 letter to the CDC’s Dr. Deborah Dowell, one of the co-authors of the 2016 guideline. “We are suggesting this change because evidence-based reviews and expert consensus have found the long-term use of opioids is likely to be counter-productive for fibromyalgia, chronic headache and chronic axial low back pain.”

PROP didn’t get its explicit statement in 2016, but it may be getting another chance as the CDC revises and possibly expands its guideline.

Little Support for Guideline Expansion

In our survey, patients and providers seem to be wary about expanding the guideline to include treatment recommendations for specific conditions. Only about 40% support guidelines for low back pain, fibromyalgia and short-term acute pain. Many believe the CDC has already gone too far and some wonder where the agency gets the regulatory authority to create guidelines for medical conditions.    

“CDC should never have developed and issued opioid prescribing guideline, as such work falls outside CDC's mission and expertise. If guidelines are needed, FDA should write,” one respondent said.

“The CDC guideline would be fine, if if were not being weaponized. There is nothing wrong with having guidelines for non-specialists. However, insurance companies have grabbed hold of it and are now using it to deny coverage of what they think is outside the guidelines,” said another.  

“Pain and it’s treatment should have a guideline but with the acknowledgment that its never one size fits all,” a patient wrote. “Some standardized measures are useful to help physicians make decisions in acute, cancer, non-cancer pain, and non-narcotic options should be sought first.”

SHOULD CDC MAKE RECOMMENDATIONS FOR TREATING LOW BACK PAIN, FIBROMYLAGIA AND OTHER PAIN CONDITIONS?

Strong Opposition to 90 MME Limit

If there’s anything that patients and providers want changed, it’s the guideline’s recommended dose limit of 90 MME (morphine milligram equivalent). Although voluntary, the daily dose limit has been rigidly applied by many doctors, pharmacists, insurers and regulators. As a result, patients who’ve taken higher doses of opioids for years — and done it safely — suddenly found themselves being tapered to 90 MME or less.

“My spouse has Ehlers Danlos Syndrome. Her chronic severe pain kept her bedridden for years until a doctor found an opioid regimen that worked. She had her life back and was able to function out of bed. This worked for over 12 years,” one man told us.

“Now, the CDC guidelines have caused local practitioners to require cutting her MME equivalent per day from about 300 to 90. They fear liability. When they discuss tapering and are confronted with the question, ‘But this is a genetic tissue disorder, it is not going to taper away,’ they have nothing to say except to point the finger at the CDC and say they are afraid of being sued. This is going to put her back in bed and, I'm afraid, kill her.”

Asked what changes should be made to the CDC’s recommended dose limit of 90 MME, nearly 87% said there should be no limit on opioid dosages.

“My doctor drastically reduced my medication and I suffer for it. Can hardly walk, can't function like I want to, no one cares as long as its 90 MME. Doesn't matter if I require higher dose and have tolerated it just fine for years,” a patient said.

“I was force tapered in 2016. I've been unable to fill legitimate prescriptions several times and denied meds by my insurance unless I use what they say is equivalent,” a patient told us.

“I was forced tapered from 550mg down to 90mg without my consent,” another patient wrote.

“Pretty much told that I would either take the lower prescribed dose or suck it up without pain relief,” said another.

WHAT CHANGES SHOULD BE MADE TO CDC'S DOSE LIMIT OF 90 MME?

“All of a sudden you can't have your regular prescription. Doesn't matter if it effects my health adversely. Blood pressure through the roof, NEVER had that problem before with it, but keep that 90 MME no matter what. Doctors sympathize but they are too scared to help you,” another patient said. “This rule doesn't help chronic pain patients at all and it doesn't stop overdoses. It needs to change.”

“My physician has been told by the hospital board that they have to reduce the amount of pain medication to ALL patients to an equivalent of 90mg. I have been taken off 70mg of my pain medications that I have taken for over 20 years,” wrote yet another patient.

“The doctor has told me he must continue to taper me more. He knows I am suffering but his hands are tied. The CDC must allow physicians that are experts in the pain management field to treat their patients as individuals. I have a lot more to say but can not type anymore as it causes me great amount of pain to use my hands and fingers.”

We received thousands of comments like these from patients, doctors, caretakers, spouses and loved ones.

One of the more poignant ones came from an intractable pain patient who considers herself lucky to have a doctor who slowly tapered her down to 90 MME. That doctor has now retired. She fears for her future and those of other patients.

“It’s my feeling we’ll look back on all this one day and realize this was in every aspect of the word a genocide; an attack on the weakest of us, the ones who most needed protection, but were mercilessly denied it.”

— Intractable Pain Patient

“I’ve managed to get to 90 MME from a dose much higher, as I was most definitely a high dose patient, but it only happened because I had good care for all those years,” she said. “I experience more nerve pain now than ever before, and I still very much fear being cut off.

“God bless any doctor or human being who’s willing to support us during this terrible most tragic of times. We’re being put in a position to lose all semblance of pain management for good if this downward spiral is allowed to continue. That’s such an inhumane and ugly thing to do, after countless lovely vibrant lives have been snuffed out by the lack of it already. It’s my feeling we’ll look back on all this one day and realize this was in every aspect of the word a genocide; an attack on the weakest of us, the ones who most needed protection, but were mercilessly denied it.”

(PNN’s survey was conducted online and through social media from March 15 to April 17. A total of 4,185 people in the United States participated, including 3,926 who identified themselves as chronic, acute or intractable pain patients; 92 doctors or healthcare providers; and 167 people who said they were a caretaker, spouse, loved one or friend of a patient. Thanks to everyone who participated in this valuable survey. To see the full survey findings, click here.)

Study Finds Little Evidence to Support Use of Acetaminophen

By Pat Anson, PNN Editor

Acetaminophen is the most widely used over-the-counter pain reliever in the world — the active ingredient in Tylenol, Excedrin, and hundreds of pain medications. The U.S. Centers for Disease Control and Prevention considers acetaminophen a “first-line” treatment for low back pain, osteoarthritis and migraine.

But a comprehensive review published in the Medical Journal of Australia found little or no evidence to support the use acetaminophen for most pain conditions. Researchers at the University of Sydney analyzed 36 studies involving over 19,000 people and concluded that the pain-relieving benefits of acetaminophen – known as paracetamol outside the U.S. -- are modest, at best.

“For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain,” wrote senior author Christopher Maher, PhD, a professor at the Sydney School of Public Health.

Maher and his colleagues looked at 44 pain conditions often treated with paracetamol, and could find only four for which there is high-quality evidence:

• Knee and hip osteoarthritis

• Tension headache

• Perineal pain after childbirth

• Craniotomy

Evidence for the other 40 pain conditions was low quality or inconclusive, including:

• Acute and chronic low back pain

• Major surgery

• Dental surgery

• Migraine

• Rheumatoid arthritis

• Hip fracture

• Cancer pain

• Neuropathic pain

“While paracetamol is widely used, its efficacy in relieving pain has been established for only a handful of conditions, and its benefits are often modest. Although some trials have evaluated regimens that may have underestimated its utility, the clinical application of paracetamol is primarily guided by low quality evidence, at best,” researchers said.  

A 2015 study in the British Medical Journal also found that paracetamol was ineffective for low back pain and provided little benefit to people with osteoarthritis.

In recent years, some U.S. hospitals have started using paracetamol as an alternative to opioids for post-operative pain, a practice not supported by the Australian study.

One limitation of the University of Sydney review is that most of the studies that were evaluated only used a single dose of paracetamol, which does not reflect its typical use.  Perhaps for that reason, researchers found that adverse events were similar for patients receiving paracetamol or a placebo.

Over 50 million Americans use paracetamol (acetaminophen) each week to treat pain and fever. Long-term use has long been associated with liver, kidney, heart and blood pressure problems. Acetaminophen overdoses are involved in about 500 deaths and over 50,000 emergency room visits in the U.S. annually.

Is Your Spinal Pain Inflammatory or Neuropathic?

By Forest Tennant, PNN Columnist

Every person with Adhesive Arachnoiditis (AA) or other spinal canal disorder needs to determine if their pain is primarily inflammatory, neuropathic or both. Why? The treatments are different.

AA is fundamentally an inflammatory disease that involves two different intraspinal canal tissues: the cauda equina nerve roots and the arachnoid-dural covering of the spinal canal. The inflammation causes damage to the nerve roots, so electricity either can’t pass or it doesn’t pass in a smooth, natural flow.

Nerve damage that blocks or alters electricity conduction is called “neuropathic” pain. AA usually has both inflammatory and neuropathic pain, but the inflammation may resolve and leave behind damaged nerve roots and neuropathic pain.

The inflammatory and neuropathic pain of AA may also develop into Intractable Pain Syndrome, which is constant, incurable pain with cardiovascular, endocrine (hormonal) and autoimmune complications.

Persons with AA usually need to treat both kinds of pain – inflammatory and neuropathic --   but one type may be predominant. A blood test for inflammatory markers is helpful, but not totally diagnostic.

If your pain improves with a trial of ketorolac (1 or 2 injections) or a corticosteroid (Medrol Dose Pak or dexamethasone), you have active inflammation that must be treated. We also recommend botanical anti-inflammatory agents, such as curcumin/turmeric, Andrographis and serrapeptase.

Prescription medications for neuropathic pain include gabapentin (Neurontin), diazepam, carisoprodol, topiramate, Lyrica and Cymbalta.

Every person with AA of the cervical and/or lumbar spines should experiment with topical medications, such as the Salonpas patch, lidocaine gel or patch, Voltaren gel and diclofenac (prescription needed).

Topical medication that is applied and massaged into the skin may dissolve through the tissues to the inflamed or damaged area. On average, you can expect 10 to 25% additional pain relief, plus the potential to permanently reduce your pain. Sometimes topical  medication will relieve painful areas that other drugs taken orally or by injection cannot reach.

Forest Tennant is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from bulletins recently issued by the Arachnoiditis Research and Education Project. Readers interested in subscribing to the bulletins should send an email to tennantfoundation92@gmail.com.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

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.

Home-Based Virtual Reality Reduces Chronic Low Back Pain

By Pat Anson, PNN Editor

A new clinical study has found that home-based virtual reality (VR) therapy can significantly reduce pain levels in people suffering from chronic lower back pain. Patients who watched VR programs also reported better mood, reduced stress and that pain interfered less with their sleep.

The study, published in the Journal of Medical Internet Research, is the first controlled trial to compare home-based VR therapy to a “sham” or placebo treatment for chronic pain. The research was funded by AppliedVR, a Los Angeles-based company that is developing therapeutic VR content to help treat pain and other conditions.

Eighty-nine people used the company’s EaseVRx headset daily for eight weeks, immersing themselves in relaxing and meditative VR programs designed to make their pain seem less important, similar to cognitive behavioral therapy. A control group received the sham treatment, watching routine nature scenes with the headset. All participants had chronic low back pain for at least six months.   

By the end of the study, 87 percent of people in the VR group reported less pain intensity, with nearly two-thirds experiencing at least a 30% reduction in pain compared to the control group. There were also significant improvements in sleep, mood and stress in the VR group.

Importantly, the improvements in pain and other symptoms were cumulative over time – meaning the relief was long-lasting and not just when people were watching VR programs.

“If you look at the results graph, you’re able to see the trajectory of pain and pain intensity very reliably declining over the course of the eight weeks. It’s a really strong time trend. It’s not just a random effect,” explained Beth Darnall, PhD, AppliedVR’s chief science advisor.

You can see the graph below. Over the course of 56 days, average pain intensity fell by 43% in patients using the EaseVRx headset, compared to 23% in the control or sham group.

JOURNAL OF MEDICAL INTERNET RESEARCH

Most of the research to date on VR therapy has focused on treating acute pain in hospitalized patients. AppliedVR is trying to demonstrate that virtual reality can also be used to treat chronic pain at home. A small study released last summer showed that home-based VR therapy reduced pain in people with fibromyalgia and chronic low back pain.

Darnall was hesitant to say if there were any pain conditions that VR therapy might not useful for.

“At the end of the day, pain is pain,” said Darnall, who is a pain psychologist at Stanford University. “This basic approach, in which we’re equipping people with self-regulatory skills, is going to be beneficial and broadly applicable for every pain condition.

“We have multiple studies in progress that are testing this device on different populations. It’s really going to be an exciting year, because there’s going to be an explosion of research that’s really going to inform our understanding of how this may help people across different disease conditions.”   

AppliedVR’s headset received breakthrough device designation from the Food and Drug Administration last year. The company hopes to get clearance from the FDA later this year to begin selling the devices. Due to a recent decision by Medicare to start covering breakthrough medical devices, the company is hopeful that private insurers will also start paying for VR therapy. 

Stem Cells Restore Function in Patients Paralyzed by Spinal Cord Injuries

By Pat Anson, PNN Editor

Intravenous injection of mesenchymal stem cells (MSCs) in patients paralyzed by spinal cord injuries led to significant improvement in their motor functions, according to a team of researchers at Yale University and Sapporo Medical University in Japan.

The study findings, published in the Journal of Clinical Neurology and Neurosurgery, focused on 13 patients who suffered spinal cord injuries (SCIs) after falls or trauma. Some lost the ability to use their arms and legs, while others suffered coordination and sensory loss, or experienced bowel and bladder dysfunction.

For more than half of the patients, substantial improvements in motor function were observed within weeks of being injected with autologous MSCs derived from their own bone marrow. Although this was a small observational Phase 2 study, researchers are excited by the findings.

"The idea that we may be able to restore function after injury to the brain and spinal cord using the patient's own stem cells has intrigued us for years," said senior author Stephen Waxman, MD, a professor of neurology, neuroscience and pharmacology at Yale. "Now we have a hint, in humans, that it may be possible."

One of the patients profiled was a 34-year-old man who was left partially paralyzed and bedridden after a fall. He received an intravenous injection of MSCs 47 days after his injury. Two weeks after the infusion, voluntary movement was restored to his lower extremities and he was walking with the support of a walker.

In another case, a 47-year-old man left bedridden after a diving accident showed rapid improvement after a stem cell infusion. He was able to drive a wheelchair the next day, walk and climb stairs after two weeks, and eat independently after eight weeks.

Other patients paralyzed after similar injuries were able to breath again without assistance, regain control of their bowel functions, and perform independent living tasks such as dressing and grooming.

“Although this initial case study was unblinded and uncontrolled, the SCI patients appeared to demonstrate a tendency of relatively rapid improvement of neurological function that was often apparent within a few days following infusion of MSCs,” researchers said.

“We would emphasize that this case series describes an early study on a small number of patients. In addition to being unblinded and uncontrolled, this study has a number of limitations. We cannot rule out observer bias nor a contribution of surgical intervention to recovery in cases where this intervention occurred, or spontaneous recovery.”

Other case studies have also shown that stem cells can restore motor and sensory function in patients paralyzed by spinal cord injuries.

The Mayo Clinic reported in 2019 that a California man paralyzed from the neck down in a surfing accident was able to walk again after being injected with his own stem cells. Researchers emphasized the man was a “super-responder” and that other paralyzed patients injected with stem cells don’t have such a dramatic recovery.

According to the National Spinal Cord Injury Statistical Center, over 17,000 Americans suffer spinal cord injuries each year. Chronic pain is a serious problem that can result from SCI, affecting about two-thirds of patients, with one out of three reporting their pain as severe.

Promising Results for Stem Cell Treatment of Degenerative Disc Disease

By Pat Anson, PNN Editor

An Australian regenerative medicine company has released positive results from a Phase III randomized trial showing that a single injection of its proprietary stem cell product can provide long-term relief for people with chronic lower back pain caused by degenerative disc disease.

Mesoblast Limited said the results are so promising it plans to meet with the U.S. Food and Drug Administration to discuss ways to accelerate approval of the drug as a treatment that reduces the use of opioid pain medication.

The company’s stem cell product -- remestemcel-L -- has been under development for several years. It uses mesenchymal precursor cells taken from the bone marrow of healthy donors to reduce inflammation by inhibiting the production of pro-inflammatory cytokines by white blood cells.

Sixty percent of the patients in the clinical trial who were injected with remestemcel-L reported minimal or no pain after 12 months. After 24 months, 54 percent reported little or no pain, with the greatest pain reduction in patients in the early stages of degenerative disc disease. Many patients also significantly reduced their use of opioids during the study period.

“The durable pain reduction for at least two years from a single administration indicates that rexlemestrocel-L has the potential to change the treatment paradigm for chronic low back pain due to inflammatory disc disease, a condition that affects as many as seven million patients across the United States and Europe, and to prevent or reduce opioid use and dependence,” Dr. Silviu Itescu, CEO of Mesoblast, said in a statement.

Over 400 patients were enrolled in the Phase III trial, which was conducted at 48 sites around the world, mostly in the United States. Although Mesoblast told physicians and patients not to change any medications during the trial, after 24 months there was a 40% reduction in opioid use in patients injected with rexlemestrocel-L. Those who were given a placebo saline injection increased their daily opioid consumption.

In a previous study of patients with chronic lower back pain who did not respond to conventional treatment, a single injection of remestemcel-L also reduced pain for at least two years.

The FDA has prioritized the development of new pain treatments that reduce the use of opioids. Although the agency has taken a dim view of some stem cell therapies as “unproven and potentially dangerous,” Mesoblast believes the FDA will be more open-minded about its rexlemestrocel-L treatment. Last year the agency approved an investigational new drug application for rexlemestrocel-L as a therapy for COVID-19.

“We now have two studies that show significant pain reduction and we’re fully prepared to have a discussion with FDA on a path forward,” said Mesoblast Chief Medical Officer Dr. Fred Grossman. “We’re going to get into discussions to see if there’s an accelerated path. Or, if we do need to do another study, we now have a very defined patient population where we see significant pain reduction.”

Antidepressants Ineffective for Back Pain and Osteoarthritis

By Pat Anson, PNN Editor

Antidepressants like duloxetine (Cymbalta) are increasingly being prescribed to treat various types of pain, but a new study shows the medications are largely ineffective for people suffering from chronic back pain or osteoarthritis and may even cause harm.

Many clinical guidelines recommend using antidepressants as pain relievers – even when depression is not involved -- yet evidence supporting that use is uncertain. To address that knowledge gap, researchers at the University of Sydney reviewed data from 33 controlled trials involving more than 5,000 adults who took antidepressants for low back or neck pain, sciatica, or hip or knee osteoarthritis.

Their findings, published in The BMJ, show that for people with back pain the effects of antidepressants were too small to be worthwhile, but for those with osteoarthritis there may be a small beneficial effect.

“The use of antidepressants to treat people with chronic back pain and osteoarthritis is increasing worldwide, but prior to our work, it was not clear whether antidepressants relieved pain or were safe,” said lead author Dr. Giovanni Ferreira, PhD, a postdoctoral research fellow at the Institute for Musculoskeletal Health at the University of Sydney. 

“We conducted a review of all randomised clinical trials evaluating the efficacy of antidepressants for people with back pain or knee osteoarthritis and found that for back pain the antidepressants were either ineffective or provided a very small effect, which was unlikely to be perceived as worthwhile by most patients. For people with osteoarthritis, effects were still small, but could be potentially perceived as worthwhile by some patients” 

Ferreira and his colleagues reviewed six classes of antidepressants: serotonin-noradrenaline reuptake inhibitors (SNRIs); selective serotonin reuptake inhibitors (SSRIs); noradrenaline-dopamine reuptake inhibitors (NDRIs); tricyclic antidepressants; and tetracyclic antidepressants. 

Results showed that SNRIs such as duloxetine reduced back pain after three months, but the benefits were so small they were unlikely to be considered clinically important to most patients. SNRIs had a slightly stronger effect on sciatica and osteoarthritis pain. 

Tricyclic antidepressants were ineffective for back pain, but might reduce pain in people with sciatica, although the evidence for that was weak.  

Industry Funded Studies 

Importantly, about two-thirds of people taking SNRI antidepressants experienced an adverse event such as nausea, fatigue, mood swings and weight gain.

“Many people are being treated with these medications that may not be helping their pain and may be doing them harm,” said Ferreira, adding that doctors need to be upfront with patients about possible side effects.

Researchers say the long-term effects of antidepressants prescribed for chronic pain are not well known and many of the studies that do exist were sponsored by industry, raising the risk of bias. 

“Many people are being treated with these medications that may not be helping their pain and may be doing them harm.”

— Dr. Giovanni Ferreira

“Large, definitive trials free of industry ties are urgently needed to evaluate the efficacy of antidepressants,” Ferreira said. “There needs to be more transparency about how evidence coming from those trials is appraised by guideline panels. A good starting point would be to consider all industry-funded trials to be at high risk of bias, and downgrade the strength of recommendations where industry-sponsored trials represent an important part of the available evidence.”

The Food and Drug Administration recently approved duloxetine as a treatment for fibromyalgia in pediatric patients, largely on the basis of a small trial conducted by Eli Lilly, Cymbalta’s manufacturer. Children enrolled in the study did show a modest improvement in pain, but several of them had serious adverse events, including two attempted suicides, suicidal thoughts, an intentional drug overdose, depression and hallucinations.

In their published findings in the journal Pediatric Rheumatology, Eli Lilly researchers downplayed the adverse events associated with duloxetine, saying they were not drug related or “not significantly different” than those of children on placebo. The two attempted suicides aren’t even mentioned.

A common complaint of patients who take duloxetine is how quickly they become dependent and what happens when they stop taking the drug. Many complain of severe withdrawal symptoms, including electric-like sensations called “brain zaps.”

Duloxetine’s checkered history is well known at the FDA. The agency’s adverse events reporting system has recorded nearly 35,000 cases involving duloxetine since 2007, most of them classified as psychiatric disorders. Over 4,000 of those adverse events resulted in death.

Why Water Soaking Works

By Forest Tennant, PNN Columnist

There is no medical treatment older than water soaking. It is legend and still works. Adhesive Arachnoiditis and other Spinal Canal Inflammatory Disorders (SCID’s) are particularly helped by water soaking – so much so that we consider it an essential treatment.

Why water soaking relieves pain has been a mystery until recent times. It is known that damaged or “dead” nerves won’t conduct  the body’s natural electric currents, so electricity backs up and is trapped or retained in body tissues. The result is more inflammation and pain “all over.”

Electricity has a negative charge and water tends to have a positive charge, so it pulls out excess electricity from the body, reducing inflammation and pain. If the water contains a mineral, it will pull out even more electricity. That is why mineral hot baths and Epsom Salts are so effective.

The lumbar-sacral spinal canal is loaded with nerve roots. They constantly conduct electric currents that go from the spinal cord to the legs, feet, bladder, sex organs and intestine.

Any damage, by any cause, to the spinal canal nerve roots causes a backup of electricity which is painful and produces even more inflammation. To prevent disease progression, daily water soaking can be most helpful.

Types of Water Soaking

You don’t have to have a jacuzzi or pool to do water soaking. A bathtub is great, but most of us take showers. When you shower, keep the water as hot as you can stand, and massage and stretch your back muscles as the hot water runs over your back. Soaking for 10 to 15 minutes in a jacuzzi, pool or bathtub is preferable, but hot showers morning and night is about as good.

Don’t forget the Epsom Salts. The body normally excretes its excess electricity into the air, mainly through nerve ends in the hands, head and feet. Foot soaking, particularly with Epsom Salts or other herbal salts, is an age-old remedy that attracts the electric currents that travel down the sciatic and other leg nerves.

Another soaking technique is a warm, water-soaked towel or other wet wrap placed over the lower back for 5-10 minutes. Remember, water soaking isn’t an “all wet” idea.

Forest Tennant is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from bulletins recently issued by the Arachnoiditis Research and Education Project . Readers interested in subscribing to the  bulletins should send an email to tennantfoundation92@gmail.com.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Exercise Is Best Treatment for Low Back Pain, But Why?

By Pat Anson, PNN Editor

There has long been a consensus that the best way to treat chronic lower back pain (CLBP) – the world’s leading cause of disability – is by staying active and exercising. But a new study by Australian researchers failed to identify precisely why exercise is beneficial.

“A lot of treatments have stemmed from studies for people with CLBP, but the one with the most consistent evidence of benefit is exercise,” says senior author Matt Jones, PhD, an exercise physiologist, clinician and researcher at the UNSW Sydney School of Medical Sciences. “Despite decades of research in the area and more than 100 studies we analysed in our review, we still do not have a good idea of why exercise might be effective for CLBP.”

Jones and his colleagues recently reported their findings in the journal Musculoskeletal Science and Practice. They reviewed 110 research papers on CLBP conducted in Australia, United States, China, Brazil and Europe, and found little agreement on why researchers thought exercise relieved lower back pain.

“Researchers proposed common reasons as to why exercise was beneficial, including improvements in fitness – for example, core stability, aerobic fitness – and improvements in mood and confidence,” Jones said. “But the effects of these proposed reasons on outcomes for people with CLBP were seldom examined in the papers.

“There have been trends in research over time, where everyone focuses on a ‘flavour of the month’ – like motor control or McKenzie therapy, for example – but because the effects of exercise are broad and it impacts on many different systems in the human body, it’s difficult for researchers to pinpoint exactly why they think it might be benefiting people with pain.”

At any given time, over 500 million people worldwide are suffering from CLBP, which is “non-specific” back pain lasting three months or longer – not the severe back pain caused by degenerative disc disease, spinal injuries, arthritis and other chronic conditions. CLBP mostly affects adults of working age in lower socioeconomic groups, who often have physically demanding jobs.

A 2018 review published in The Lancet by an international team of researchers found that CLBP is often treated with bad advice, inappropriate tests, risky surgeries and painkillers. The authors said there was limited evidence to support the use of opioids for low back pain, and epidural steroid injections and acetaminophen (paracetamol) were not recommended at all.

“The majority of cases of low back pain respond to simple physical and psychological therapies that keep people active and enable them to stay at work,” said lead author Professor Rachelle Buchbinder of Monash University in Australia. “Often, however, it is more aggressive treatments of dubious benefit that are promoted and reimbursed.”

Jones said the aggressive treatments may not work because they don’t address underlying psychological reasons for back pain.

“Chronic pain is tricky and there are a lot of factors that can contribute to it – so, it's not simply biological aspects of tissue damage, but there are psychosocial elements at play, as well things like a person’s mood or confidence in their own abilities to do something,” he said. “Today’s evidence suggests CLBP likely comes from the brain and nervous system being a bit over-protective and generating a pain response – despite no obvious physical damage to the body.”

Although his review did not address what specific exercises were most effective for CLBP, Jones and his team recommended 33 “mechanisms” that people can use to relieve back pain, such as building muscle strength and flexibility or through social support and coping strategies.

“Many scientists have investigated this question before and the short answer is, there are no specific exercises recommended to alleviate CLBP,” he said. “But there are literally hundreds of studies on exercise for people with chronic pain, not only CLBP, and researchers consistently find exercise is one of the most effective treatments – it might not cause huge reductions in pain and disability, but it does help.”

Ehlers-Danlos Is Common Cause of Intractable Pain

By Forest Tennant, PNN Columnist

Ehlers-Danlos Syndrome (EDS) is the best known of the hereditary collagen disorders. From birth, persons with EDS are preprogrammed to start dissolving collagen at some location in the body, as it causes a defect in the way collagen is produced or maintained throughout all tissues.

The fine and soft tissues that are the most susceptible to dissolution are found in the joints, ligaments, eyes, spine, gums and intestine. When these tissues deteriorate and begin to dissolve, inflammation, pain and neurologic impairments begin. The tissue may or may not rebuild and usually leaves permanent damage, pain and/or disability.

Collagen deterioration may start in childhood or middle age. An early sign is being double-jointed or extremely flexible.

It is unknown currently what the exact mechanism is, or what precipitating factors such as virus or trauma that initiate this reaction. Regardless, collagen dissolution will move to a new and different locations once the hereditary preprogramming begins.

EDS commonly hits the spinal canal and spine. The first major problem may be a cerebral spinal fluid leak, protrusion of a disc, Tarlov cyst or arachnoiditis. Given its predilection to hit the spine, EDS may produce the complication of Intractable Pain Syndrome (IPS). In fact, it seems to be emerging as the first or second most common cause of IPS.

EDS Screening Test

Our research has found that a high percentage of patients who have EDS don’t know it. If you have developed a spine or pain problem without an injury or other obvious cause, you should be screened for EDS.

This questionnaire was recently published to help screen people for EDS.   

1. Do you have pain in multiple locations?

2. Do you have extreme fatigue?

3. Are you clumsy sometimes and fall or walk into objects?

4. Are some of the joints in your hands, feet, elbow, hips or knees “loose” or quite flexible?

5. Have you had a lot of sprains or joint dislocations?

6. Is your skin thin in places?

7. Are you double-jointed or able to bend your fingers, arms, or ankle backward?

8. Are your hands and feet cold much of the time?

9. Do you bruise easily or have bruises that suddenly occur?

10.  Is your skin “stretchy” in some places?

11.  Are you constipated a lot?

12.  Do you suffer from heart burn or frequent episodes of food regurgitation? 

If you answered “Yes” to 6 or more of the 12 questions, you should see a doctor and have the diagnosis confirmed by a genetic test or skin biopsy.

If you have EDS or a hereditary collagen disorder, there are foods, supplements and hormones you can take to help restore and rebuild lost tissue. Click here to see them. These tissue building recommendations from the IPS Research and Education Project are meant to complement and supplement your treatment program, but are not a substitute for inflammation and pain control.

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

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