Experimental Brain Implant Automatically Relieves Pain

By Pat Anson, PNN Editor

An experimental brain implant that automatically detects and relieves pain in laboratory animals has the potential to be adapted for human use, according to researchers at NYU Grossman School of Medicine. The computerized device is the first of its kind to target both acute and chronic pain, and may also be effective in treating anxiety, depression, panic attacks and other brain-based disorders.

“Our findings show that this implant offers an effective strategy for pain therapy, even in cases where symptoms are traditionally difficult to pinpoint or manage,” said senior author Jing Wang, MD, an Associate Professor of Anesthesiology at NYU Langone Health.

The technology, known as a closed-loop brain-machine interface, detects brain activity in the anterior cingulate cortex, a region of the brain that is critical for pain processing. A computer linked to the device identifies pain signals in real-time, triggering a therapeutic stimulation of another region of the brain, the prefrontal cortex, to ease pain sensations.  

Wang and his colleagues installed the tiny electrodes in the brains of dozens of rats and then exposed them to carefully measured amounts of pain. The animals were closely monitored to see how quickly they moved away from a source of acute pain.

The study findings, published in the journal Nature Biomedical Engineering, showed that rats withdrew their paws 40 percent more slowly from the pain source when the device was turn on. In addition, animals in acute or chronic pain spent about two-thirds more time in a chamber where the device was turned on than in another chamber where it was not.

Researchers say the implant accurately detected pain up to 80 percent of the time. Since the device is only activated in the presence of pain, it lessens the risk of overuse, tolerance and addiction.

“Our results demonstrate that this device may help researchers better understand how pain works in the brain,” says lead investigator Qiaosheng Zhang, PhD, a doctoral fellow in the Department of Anesthesiology, Perioperative Care and Pain at NYU Langone. “Moreover, it may allow us to find non-drug therapies for other neuropsychiatric disorders, such as anxiety, depression, and post-traumatic stress.”

Zhang says the implant’s pain-detection properties could be improved by installing electrodes in other regions of the brain besides the anterior cingulate cortex. He cautions, however, that the technology is not yet suitable for use in people. Researchers are investigating whether less-invasive forms of the implant can be adapted for human use.

Brain implants – also known as deep brain stimulators -- are currently used to prevent seizures and tremors in people with Parkinson’s disease and epilepsy.

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.

Why Good Nutrition Is Needed for Intractable Pain Syndrome

By Forest Tennant, PNN Columnist

If you have Intractable Pain Syndrome (IPS) or a condition that commonly causes IPS, such as arachnoiditis, adhesive arachnoiditis, cauda equina syndrome, Ehlers-Danlos Syndrome, traumatic brain injury, stroke or Complex Regional Pain Syndrome (CRPS), you should underpin your treatment program with a nutritional one.

Our research and experience clearly tell us that a proper nutrition program is essential for pain relief and to prevent the progression of IPS. Without a good nutritional program, neither medication or other medical measures will be very effective.

Persons who have IPS develop what is known as a “catabolic state.” The term means that the cellular matrix of the body is slowly degenerating, rather than its normal state of constant cellular regeneration, known as an “anabolic state.”

In IPS, cells and tissues inside and outside of the brain and spinal cord (CNS) progressively degenerate because of IPS’s combined effects of inflammation, hormonal deficiencies, and autoimmune attacks on tissues. If one has a genetic connective tissue/collagen disorder (EDS or other), then cellular catabolism or deterioration is grossly multiplied.

Cellular deterioration in IPS initially attacks small nerve fibers and the small cells in the CNS and skin, but later other tissues may be involved. Muscle mass deteriorates and is replaced by fatty tissue, so weight gain occurs. In late stages of catabolism, severe muscle loss may occur, giving the patient the appearance of starvation and emaciation. Weakness and fatigue set in. Memory, reading ability and logical thinking decline. Medications, including opioids, may not be as effective as they once were.

Persons with IPS must daily attempt to control catabolism through proper nutrition, which helps stop disease deterioration, reduces inflammation, regrows damaged nerves (neurogenesis), alkalizes body fluids, and improves pain relief and energy.

There are five basic components of an IPS nutrition program:

1. Eat protein every day and include protein in ALL meals.

2. Eat green vegetables, and select fruits and nuts

3. Control cholesterol and glucose

4. Daily multi-vitamins and minerals

5. Daily supplements for nerve regrowth and inflammation

Protein is Key

The most critical component of an IPS nutrition program is protein. IPS tends to decrease a desire for protein and promotes a craving for sugar and starches. The major protein foods are beef, pork, lamb, chicken, turkey, seafood, cottage cheese and eggs. Protein drinks and bars can also be used as alternatives.

Why is protein so important? It contains all the fuel (amino acids) needed by the body to make more endorphin, serotonin, dopamine, norepinephrine, insulin and other hormones. Protein builds tissue, repairs cells and helps stabilize blood sugar. Meals with no protein will likely increase pain and inflammation, which prevents healing.

Foods that are mainly sugar and starches (carbohydrates) cause sugar (glucose) to rise in the blood. Fatty foods cause cholesterol to raise in the blood. New research shows that high levels of glucose and fat may cause inflammation and damage to the neurotransmitters and receptor systems that control pain. 

IPS patients should have their glucose and cholesterol levels tested on a regular basis. If abnormally high or low, work with your medical practitioner to normalize them.  

You can help by reducing sugars and fats in your diet, and by eating meals on a regular schedule, even if you are not hungry. This will help balance your glucose and lessen your pain over time.   

You may also want to consider a gluten free trial. Stop eating bread, cereal, noodles and other foods containing gluten for one week to see if you feel better. 

Green Is Good 

Vegetables, fruits and nuts can also help reduce inflammation, alkalinize your body fluids, and promote tissue healing. The best green vegetables are broccoli, kale, brussel sprouts, asparagus, green beans, spinach, snap peas, chard, mustard greens, turnip greens, collards, and cabbage. Avoid eating potatoes and corn, which are loaded with carbohydrates. 

The best fruits are blueberries, pineapple, raspberries, blackberries, cherries, oranges, plums, apples, strawberries, and peaches. Avoid eating bananas. The best nuts to eat are pistachios, almonds and peanuts. 

To help regrow damaged or diseased tissues, take daily supplements containing vitamins B12 and C, collagen, amino acids and natural hormonal agents such as colostrum or DHEA. A daily multi-vitamin and mineral tablet is also helpful, along with a daily plant-based anti-inflammatory agent such as curcumin/turmeric or quercetin. 

Ask yourself: Is what I am eating right now helping or hurting? If you don’t know or want more information, the IPS Research and Education Project has just published a 12-page nutritional program designed specifically for people with IPS. You can download a free copy by clicking here.  

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

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

Clearing: What to Expect From a New Digital Pain Care Company

By Pat Anson, PNN Editor

The last few years have seen rapid growth in telemedicine and the digital healthcare market. You can consult with a doctor online and get treatment for just about every ailment, from acne and allergies to hair loss and erectile dysfunction.

Clearing, a subscription-based digital health service, is the first to focus exclusively on treating chronic pain, a global market worth over $80 billion a year that has 50 million potential customers in the U.S. alone. The company recently announced $20 million in funding from private investors.

“What we’re trying to do is build a digital healthcare platform for chronic pain sufferers,” says Dr. Jacob Hascalovici, Clearing’s co-founder and Chief Medical Officer. “We feel that chronic pain is very unique. It’s often invisible. And it really needs to start with us listening to you and designing a treatment plan that is most suitable for an individual’s needs.”

Hascalovici, a neurologist with a background in interventional pain management, says Clearing is initially focused on treating muscle, joint and neuropathic pain. At this early stage, the company does not treat more complex chronic pain conditions, such as headaches or visceral pain – the latter generally covering pain caused by infection, trauma or disease.

“Chronic pain is a very complicated space and it’s the kind of field where I think we first need to prove our ability to operate in this field. What we are focusing on primarily at launch, but by no means are restricting ourselves to, is what we call ‘Stage One’ intervention,” Hascalovici told PNN.

No Opioids or Pills

If you are curious about signing up with Clearing, there are three caveats to be aware of.

First, Clearing does not prescribe opioid pain relievers. In fact, it doesn’t offer any kind of oral medication, injection or surgery. Patients will receive topical compound creams containing over-the-counter and prescription strength analgesics (primarily NSAIDs, lidocaine and muscle relaxers), CBD cream, dietary “nutraceutical” supplements, and a personalized home exercise program you can watch online.

Second, Clearing is not covered by insurance. Depending on the plan they select, subscribers will pay anywhere from $25 to $80 a month. You’ll need to pay $10 to cover shipping and handling for the company’s “free trial.”    

Third, you’ll never actually see or speak with a physician on Clearing’s platform. All communication is handled by text messaging through the company’s online message portal.

Signing up is relatively easy. You’ll be asked to locate your pain on an anatomical figure and then describe it. Is the pain stinging? Aching? Throbbing? How long have you had it?

When I went through the signup process and indicated I had knee pain, I was never asked if it was treated or what the diagnosis was (mine was tendonitis). Hascalovici says Clearing’s physicians prefer to make their own diagnosis, although how they can do that for knee pain without ordering x-rays or imaging — or even seeing my knee — is a bit puzzling.

If you have them, you can upload your medical images to Clearing for a physician to review, although it’s not necessarily needed or even desirable.

“The imaging in chronic pain medicine doesn’t always correlate with the patient’s symptoms. And sometimes the pre-existing diagnosis can be confusing. If you’re suffering from chronic pain and the diagnosis led to a perfect treatment, then you’d probably not be in a chronic pain management doctor’s office,” Hascalovici explained.

“We’ve designed the experience at Clearing to most closely mimic an in-person visit with a chronic pain specialist. So, any patient coming into my clinical practice would first be evaluated.  We would devise a diagnostic hypothesis and then prescribe a person a home exercise program or structured physical therapy program, followed by topical pharmacotherapy. We really believe in this multi-disciplinary approach to the management of chronic pain.”

When signing up for Clearing, be prepared to give a lot of personal information, just as you would when visiting any doctor for the first time. You’ll be expected to provide a photo ID, credit card information, home address and cell phone number, among other things.

The boilerplate fine print in Clearing’s Terms of Use refers to all patient information as “User Generated Content” that becomes the property of the company and can be used “in whatever manner Clearing desires.” The company says it is not subject to HIPAA rules that protect patient privacy, but would “strive to comply” with them.

The fine print also indicates that Clearing does not consider itself a medical group or practice. All medical advice and treatment through its online platform is provided by Relief Medical Group, an independent group of practitioners where Hascalovici is co-director.

The bottom line for patients is that Clearing probably won’t work if you have severe chronic or intractable pain. But if you have simple muscle aches or joint pain, Clearing’s creams and home exercise programs may be worth a try. The low cost and convenience of telehealth are advantages over a traditional office visit, and there’s no waiting for an appointment.

MindMed Investigating Use of Psychedelics to Treat Chronic Pain

By Pat Anson, PNN Editor

A startup pharmaceutical company has announced plans to investigate the use of LSD and other psychedelics to treat chronic pain.

New York-based Mind Medicine (MindMed) is exploring the use of psychedelics to treat two pain conditions, which it is calling “Project Angie.” The company is already investigating the use of psychedelics to treat addiction, anxiety and attention deficit hyperactivity disorder (ADHD).

"With the launch of Project Angie, we seek to align closely with MindMed's core mission to improve mental health and combat substance use for the many patients in need. If we can help to develop a new paradigm to treat pain, it may have the potential to greatly reduce the use of addictive medicines such as opioids currently ravaging society and its mental health," MindMed CEO & Co-Founder J.R. Rahn said in a statement.

MindMed did not disclose what pain conditions it was developing treatments for, but it is working with researchers in Switzerland who have a Phase 2 clinical trial underway on the use of LSD to treat cluster headache. The company said it is also evaluating a second indication for a “common, often debilitating, chronic pain syndrome.”

Interest in using psychedelics to treat medical conditions has been growing in recent years. Preliminary research suggests that microdoses of LSD, psilocybin (magic mushrooms) and other psychedelics may offer a new way to treat pain. The exact mechanism in which psychedelics have an analgesic effect is not fully understood, but early research indicates that LSD can modulate serotonin receptors that help regulate pain and inflammation.

"Evidence dating back to the 1950s suggests that LSD and other psychedelics may have analgesic effects, but this treatment area remains largely untapped by companies studying psychedelics, with the majority of research focusing solely on psychiatric indications," said Rob Barrow, MindMed’s Chief Development Officer. 

The company is planning to submit a Pre-Investigational New Drug (IND) application to the Food and Drug Administration for a Phase 2a proof of concept study of LSD (lysergic acid diethylamide) in the second half of 2021.

MindMed will have to clear some high regulatory hurdles. LSD, psilocybin, MDMA (Ecstasy) and other psychedelics are classified as Schedule I controlled substances, meaning they have a high potential for abuse and currently have no accepted medical use in the United States.

Pilot Study Shows Neuromodulation Effective for Postoperative Pain

By Pat Anson, PNN Editor

In recent years, many U.S. hospitals have adopted policies that reduce or eliminate the use of opioids after surgery. For some, that means giving their patients Tylenol or Lyrica for postoperative pain. For others, it means trying neuromodulation — a non-pharmacological therapy that new research shows may have some potential.

In a placebo-controlled pilot study led by researchers at University of California San Diego, patients who received percutaneous peripheral nerve stimulation (PNS) had significant reductions in their pain levels after outpatient joint surgery.

Percutaneous PNS is a form of neuromodulation that involves the placement of a tiny wire or “lead” alongside a peripheral nerve. The implanted lead is then connected to a small external pulse generator that sends a mild electric current to the nerve, interrupting pain signals. PNS has been used for years to treat chronic pain, but this was the first clinical trial to assess its use for postoperative acute pain.    

In the pilot study, 65 adult patients scheduled for operations on their shoulders, knees or ankles had leads placed before surgery in the affected joint. After surgery, half of the patients were given neuromodulation, while the other half received a "sham" treatment with a pulse generator that appeared active but did not deliver any electric current.

Patients in both groups received opioids as needed for their postoperative pain, and after one week their pain scores and opioid use were compared.

Researchers reported in the journal Anesthesiology that the results were “much greater than we had anticipated.” Pain scores were over 50 percent lower in patients who received neuromodulation. The mean pain score (on a zero to ten scale) was 1.1 in patients receiving PNS treatment, compared to 3.1 in the sham group.

Nerve stimulation was also associated with an 80 percent reduction in opioid consumption. The median opioid dose (oral morphine equivalent) in the first week after surgery was 5 milligrams in the active treatment group, compared to 48 milligrams in the sham group.

“This multicenter, randomized, double-masked, sham- controlled pilot study provides evidence that ultra-sound-guided percutaneous peripheral nerve stimulation concurrently improves analgesia and decreases opioid requirements to a statistically significant and clinically meaningful degree for at least a week after moderately to severely painful ambulatory orthopedic surgery,” wrote lead author Brian Ilfeld, MD, a professor of anesthesiology at UC San Diego.

Ilfeld and his colleagues say the pain-relieving benefits of neuromodulation continued after the leads were removed 14 days after surgery, but they appeared to wear off after one month. They plan on conducting a larger clinical trial with 250 surgery patients and to follow them for a year to see if there are any long-term benefits from neuromodulation.

Contrary to popular belief, opioid addiction is rare after surgery. A large 2016 study found only 0.4% of older adults were still taking opioids a year after major elective surgery. Another large study in 2018 found only 0.2% of patients who took opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

Nevertheless, the now defunct American Pain Society (APS) released guidelines in 2016 that encourage physicians to use non-opioid medication such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin (Neurotin) and pregabalin (Lyrica) for post-operative pain. The APS also recommended non-pharmacological therapies such as cognitive behavioral therapy and transcutaneous elective nerve stimulation (TENS) as adjunct treatments.

The lead author of the APS guideline was Roger Chou, MD, who also co-authored the 2016 CDC opioid guideline.

Injections of Tiny Particles Reduce Osteoarthritis Knee Pain

By Pat Anson, PNN Editor

A minimally invasive procedure significantly reduces pain and inflammation caused by knee osteoarthritis, according to preliminary research being presented this week at the annual meeting of the Society of Interventional Radiology.

Geniculate artery embolization (GAE) is a relatively new procedure in which thousands of microscopic particles are injected into arthritic knees. The particles reduce inflammation by disrupting the abnormal flow of blood caused by osteoarthritis (OA), a joint disorder that causes thinning of cartilage and progressive joint damage. As the cartilage breaks down, it releases enzymes that cause inflammation and pain.

GAE takes about one to two hours, and many patients with knee OA report significant improvement in pain and physical function that can last up to a year.

"Prior to treatment, patients' knee pain had taken over their whole life," said lead researcher Siddharth Padia, MD, a professor of radiology at UCLA Health. "But after treatment, patients who initially could walk only three or four blocks were walking three miles. Some were able to do away with walking aids, such as canes, while others reported being in a better mood now that they were living without pain."

For their Phase 2 study, Padia and his colleagues enrolled 40 patients with knee OA who were not candidates for total knee replacement, and who failed to benefit from pain relievers, joint injections and physical therapy.

Catheters were inserted into arteries leading to the knees through pinhole incisions in the patients’ hips. The microscopic particles — called Embozene microspheres — were then slowly injected through the catheter into the knees. Each patient was evaluated for pain and adverse events at one week; one, three and six months; and one year after the treatment.

Researchers say patients saw benefits as soon as three days after the procedure. Average pain levels decreased from 8 out of 10 before GAE to 3 out of 10 within the first week. Most patients reported more than 50% reduction in their pain levels at the one-year follow up.

Adverse events, such as skin ulceration and small bone infarction – the death of bone tissue due to reduced blood supply -- were reported by 9 patients, but resolved without treatment.

Embozene microspheres are made by Boston Scientific and are currently used in the treatment of vascular tumors, uterine fibroids and arterial malformations. They must be carefully injected into affected tissue to prevent them from circulating in the blood and reaching healthy tissue and organs.

“This prospective trial demonstrates that GAE is highly effective and durable in reducing symptoms due to moderate to severe knee OA that is refractory to other conservative therapy, and has an acceptably low toxicity profile,” researchers concluded.

The UCLA researchers plan to conduct a larger, randomized trial to determine which patients may benefit most from GAE and the impact it has on slowing the progression of arthritis.

Results from other studies on the use of GAE are also being presented at the meeting of the Society of Interventional Radiology. One review found that GAE can be effective for patients who don't respond well to conservative treatments for knee OA, but cautioned that “definitive conclusions can't be made on the true efficacy of GAE until studies are done with longer follow up and larger patient numbers.”

Low-Dose Ketamine Effective in Treating Trauma Pain

By Pat Anson, PNN Editor

Low doses of ketamine are just as effective at treating trauma pain in emergency room patients as larger standard doses, according to a new study by researchers at Loyola University Medical Center in Chicago.

Ketamine is a non-opioid that’s been used for decades as a surgical anesthetic, but in recent years it’s increasingly being used to treat short-term acute pain in hospital emergency rooms. A standard dose of ketamine administered intravenously is 0.30 mg/kg, but Loyola researchers wanted to see if half the normal dose could be just as effective.

"We challenged the conventional ketamine dose used to treat pain," said lead study author Shannon Lovett, MD, an emergency physician at Loyola University Medical Center (LUMC). "Our study should help demonstrate that a lower dose is sufficient to treat pain."

Lovett and her colleagues recruited 98 patient volunteers who were in moderate to severe acute pain. Half received just 0.15 mg/kg of IV ketamine, while the other half received the standard dose. Both patients and providers were “blinded” on which dose was being administered.

After 15 minutes, patients in the standard dose group had a greater reduction in pain, but experienced more side effects such as dizziness, mood changes and hallucinations. After 30 minutes, adverse events and pain levels were similar in both dosing groups.

Asked if they would take ketamine again, 76% of patients in the low-dose group said yes, while only 62% in the standard dose group said they would.

"As we continue with our research, we hope to find data that supports diminished side effects with the lower dose of ketamine with equal efficacy in treating pain," said senior author Megan Rech, PharmD, an emergency medicine pharmacist at LUMC.

The study findings are reported in the journal Academic Emergency Medicine.

Researchers said there is “robust evidence supporting the use of ketamine as an alternative to traditional opioids across a wide range of doses,” but its effectiveness is usually short-lived. Ketamine does not have a significant analgesic effect after 60 minutes. It also puts patients into a hypnotic, dream-like state in which they appear awake, but are unresponsive. For that reason, ketamine is only administered under medical supervision.

A growing number of outpatient clinics provide off-label infusions of ketamine for depression, post-traumatic stress disorder (PTSD) and difficult chronic pain conditions such as Complex Regional Pain Syndrome (CRPS). The infusions are usually not covered by insurance.

A pilot study is underway to see if an oral version of ketamine and aspirin, combined in a tablet, could be used to treat pain at home.

Experimental Gene Therapy May Relieve Chronic Pain

By Pat Anson, PNN Editor

A new study by researchers at the University of California San Diego suggests that gene therapy could someday be used to treat a variety of chronic pain conditions without the use of drugs.

In experiments on laboratory mice, researchers found that temporarily repressing a gene involved in sensing pain increases pain tolerance, lowers pain sensitivity and provided months of pain relief without causing numbness. Their findings were published in the journal Science Translational Medicine.

“What we have right now does not work,” said first author Ana Moreno, PhD, CEO of Navega Therapeutics, which is developing gene therapies to treat chronic pain. “There’s a desperate need for a treatment that’s effective, long-lasting and non-addictive.”

Moreno was grad student at UC San Diego studying gene repression when she came across a paper about a genetic mutation that causes humans to feel no pain. The mutation blocks a protein -- called NaV1.7 -- that’s involved in transmitting pain signals in the spinal cord.

That’s when she came up with the idea of suppressing the gene using the CRISPR gene editing tool. Moreno was working with a version of CRISPR that uses what’s called “dead” Cas9, which lacks the ability to permanently cut DNA. Instead, it sticks to a gene and temporarily blocks its expression.

“By targeting this gene, we could alter the pain phenotype,” Moreno explained. “It’s not cutting out any genes, so there are no permanent changes to the genome. You wouldn’t want to permanently lose the ability to feel pain.

“One of the biggest concerns with CRISPR gene editing is off-target effects. Once you cut DNA, that’s it. You can’t go back. With dead Cas9, we’re not doing something irreversible.”

Moreno and UC San Diego bioengineering professor Prashant Mali, PhD, co-founded Navega Therapeutics to work on developing gene therapy as a treatment for pain.  They teamed up with Tony Yaksh, PhD, a professor of anesthesiology and pharmacology at UC San Diego School of Medicine, and developed a CRISPR/dead Cas9 system to target and repress the gene that codes for NaV1.7.

When they administered spinal injections of the system into laboratory mice with inflammatory and chemotherapy-induced pain, the mice displayed higher pain thresholds than mice that did not receive the gene therapy. The treated mice were slower to withdraw a paw from painful stimuli (heat, cold or pressure) and spent less time licking or shaking their paws after being hurt.

The treatment was still effective after 44 weeks in the mice with inflammatory pain and 15 weeks in those with chemotherapy pain. The treated mice did not lose sensitivity or display any changes in normal motor function.

To validate their results, the researchers performed the same tests using another gene editing tool called zinc finger proteins. It’s an older technique than CRISPR, but works the same way. Spinal injections of the zinc fingers into mice produced the same results as the CRISPR-dead Cas9 system.

“We were excited that both approaches worked,” Mali said. “The beauty about zinc finger proteins is that they are built on the scaffold of a human protein. The CRISPR system is a foreign protein that comes from bacteria, so it could cause an immune response. That’s why we explored zinc fingers as well, so we have an option that might be more translatable to the clinic.”

The researchers say this solution could work for a variety of chronic pain conditions, including diabetic neuropathy, sciatica, and chemotherapy pain. They believe their gene therapy platform could also be used to treat short-term acute pain.

“Think of the young athlete or wounded war fighter in which the pain may resolve with wound healing,” Mali explained. “We would not want to permanently remove the ability to sense pain in these people, especially if they have a long-life expectancy. This CRISPR/dead Cas9 approach offers this population an alternative therapeutic intervention—that’s a major step in the field of pain management.”  

Researchers at UC San Diego and Navega are planning further studies of pain-relieving gene therapy on non-human primates. Their goal is to begin human clinical trials in a couple years. Their work is funded by UC San Diego Institutional Funds and the National Institutes of Health.

Low Dose Naltrexone Emerging as Treatment for Intractable Pain

By Forest Tennant, PNN Columnist

A major advance in pain management is the discovery of low-dose naltrexone (LDN), a non-opioid medication used to treat substance abuse. When prescribed off-label, LDN not only relieves pain, but has anti-inflammatory and immune boosting properties on brain and spinal cord tissues. It is now the preferred, first drug of choice for people living with constant, intractable pain.

Only those persons who are not currently on daily opioids should take LDN. A major purpose of LDN is to prevent the necessity of daily opioids, including buprenorphine/Suboxone.

A starting dosage of LDN is usually 0.5 – 1.0 milligrams taken twice a day. The average maintenance dose is about 3 – 5mg given twice a day. The maximum dose is about 7mg taken twice a day.

LDN should ideally be a part of a multi-drug program. A nerve conduction blocker (neuropathic) agent such as gabapentin or diazepam will almost always boost pain relief. A dopamine surrogate such as Adderall, Ritalin or mucuna, is also very helpful.  Routinely recommended are standard anti-inflammatory (e.g., Ketorolac) and tissue healing anabolic agents (e.g., DHEA).

A pain flare medication should also be handy and ready. Some patients taking LDN can occasionally take a low dose of tramadol, codeine or hydrocodone for pain flares. Other flare medications include ketamine, CBD, medical marijuana, ibuprofen (800mg), oxytocin, kratom and ketorolac.

Caution and Warning

Persons who currently take daily opioids must withdraw from opioids before starting LDN. In our studies, patients sometimes became deathly ill if they took LDN while still on opioids. Severe withdrawal may set in, pain relief will diminish and, at worst, a cardiac-adrenal crisis may be precipitated.

If one has Intractable Pain Syndrome and is currently on a regimen including opioids that satisfactorily reduces pain, there is no medical reason to switch to LDN.

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.  

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. 

Advocacy Group Seeks to Expand Insurance Coverage of Ketamine

By Pat Anson, PNN Editor

A coalition of patients and healthcare providers is launching an effort to expand insurance coverage for ketamine, a non-opioid anesthetic increasingly used to treat chronic pain, depression and post-traumatic stress disorder (PTSD).

Ketamine is typically administered by infusion under strict medical supervision, a process that that can take up to an hour and cost thousands of dollars. The first goal of the Ketamine Taskforce is to get ketamine infusions fully covered by Medicare.

“Medicare doesn’t officially pay for ketamine infusions. What they will pay for is a generic infusion code similar to if someone was getting an antibiotic infused. The level of reimbursement is very low,” says Kimberley Juroviesky, a retired nurse practitioner and task force co-chair who receives ketamine infusions for Complex Regional Pain Syndrome (CRPS). 

“Since these reimbursement rates are so low, the majority of small ketamine clinics don’t accept insurance. This leaves the majority of pain patients without the pain relief they could otherwise be benefiting from.”

Ketamine is approved by the Food and Drug Administration as a surgical anesthetic, but a growing number of ketamine clinics provide off-label infusions for depression, PTSD and difficult chronic pain conditions such as CRPS. The infusions put patients into a hypnotic, dream-like state — leaving them with less physical and emotional pain once the ketamine wears off. Many insurers consider this off-label use experimental.

“If we could get Medicare to officially put ketamine on their schedule as a treatment for chronic pain, this would hopefully raise reimbursement rates to a level where all providers could afford it. Also, this would force private insurers to pay for ketamine infusions as well and no longer refuse to pay saying it’s experimental,” Juroviesky said in an email. 

PNN columnists Barby Ingle and Madora Pennington have both had ketamine infusions, Barby for CRPS and Madora while recovering from foot surgery.

“The swelling in my foot dramatically improved. Chronic, low-grade discomfort along my spine also disappeared. I felt emotional relief from past trauma, from pain and other life experiences,” Madora explained.

“I went into the hospital in a wheelchair, but walked out on my own a week later,” said Barby, after seven days of ketamine infusions. She now gets “booster” infusions four times a year and no longer takes daily pain medication.

Some ketamine users report lingering side effects, such as hallucinations and visual disturbances. Guidelines from the American Society of Anesthesiologists, American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Pain Medicine only support ketamine infusions for CRPS and short-term acute pain.

“Excluding CRPS, there was no evidence supporting ketamine infusions for intermediate or long-term improvements in pain," the guidelines warn.

The Ketamine Taskforce is working with a consortium of ketamine clinics, collecting data on the safety and efficacy of infusions. That research will be shared with the Centers for Medicare and Medicaid Services (CMS) in an effort to expand Medicare coverage of ketamine for pain and mental health conditions.

Pilot Study Launched of Ketamine Tablet as Pain Reliever

By Pat Anson, PNN Editor

Ketamine has become a trendy alternative treatment for pain, depression, anxiety and post-traumatic stress syndrome (PTSD). But to get it, you’ll need to get a ketamine infusion, injection or nasal spray – usually under strict medical supervision.

But someday you may be able to take a ketamine tablet at home, just like you would most other medications. A pilot study is underway at a New York City hospital to see if an oral formulation of ketamine and aspirin could be a useful treatment for pain.

“For certain patients, ketamine could be a real game changer,” says Dr. Joseph Habboushe, an emergency room physician and founder of Vitalis Pharmaceuticals. “If you look at pain management and what we have available to send patients home with, it’s really limited. We have NSAIDs. We have opiates. We have other things that sedate. It’s a fairly limited in choice.”

Ketamine is not an opioid and does not suppress respiration, making it relatively safe to use. But in high doses, it puts patients into a dissociative, dream-like state -- making it inappropriate for outpatient use.

What Habboushe and his colleagues hope to demonstrate is that a low dose of ketamine, when combined with aspirin, can be an effective and non-addictive pain reliever that can be used safely at home.

Their observational study at Maimonides Medical Center will enroll 25 patients with acute musculoskeletal pain, who will receive 0.5 mg of oral ketamine administered simultaneously with 325mg of aspirin. Pain scores and adverse events will be recorded at various intervals for up to two hours.

The study is being led by Sergey Motov, MD, an emergency room physician who is passionate about finding alternatives to opioids.

VITALIS PHARAMCEUTICALS

"The need for safe and efficacious analgesics in the emergency department and on an outpatient basis is stronger than ever," Motov said in a statement. “Taking a novel approach to orally-administered ketamine has the potential to move physicians one step closer to successfully combatting the nation's ongoing opioid crisis.”

Vitalis has developed a proprietary formulation of aspirin -- called VTS-Aspirin -- that delivers faster and stronger pain relief than traditional aspirin. Preliminary research indicates that combining VTS-Aspirin with low-dose ketamine may boost its potency.

“This is a proof-of-concept study. If we can demonstrate that ketamine will work orally, then it can be used for acute pain, maybe later chronic pain, maybe depression and all the other indications,” Habboushe told PNN. “If we can achieve that, it will be a breakthrough that will absolutely drive a lot of value to patients by reducing opiate need and reducing their pain in a very significant way. And so, it’s worth studying.”

Vitalis is also studying the use of VTS-Aspirin with fumaric acid as a treatment for multiple sclerosis that has fewer side effects. Also undergoing research is a combination of VTS-Aspirin with niacin as a treatment for high cholesterol.

Breakthrough Medical Devices to Receive Medicare Coverage

By Pat Anson, PNN Editor

Medical device manufacturers are cheering a decision by the Centers for Medicare & Medicaid Services (CMS) to have Medicare begin covering hundreds of “Breakthrough Devices” certified by the Food and Drug Administration.

The FDA’s Breakthrough Device Program was launched in 2018 to speed up the development of innovative technology for the treatment and diagnosis of life-threatening or debilitating medical conditions such as chronic pain. But FDA approval was then followed by a lengthy and costly review process for Medicare coverage, which delayed patient access to the devices.

The Medicare Coverage of Innovative Technology (MCIT) rule change allows Medicare to begin covering breakthrough devices simultaneous to FDA approval, making them immediately available to over 60 million Medicare beneficiaries. The rule change goes into effect March 15.

“Despite being deemed safe and effective by the FDA, Medicare beneficiaries have not had predictable, immediate access to innovative breakthrough devices,” CMS Administrator Seema Verma said in a statement. “CMS remains committed to transforming the health care delivery system through initiatives like MCIT that focus on results, removing government barriers to advancing innovations, fostering competition, and ensuring quicker access to the most advanced therapies for Medicare beneficiaries while providing them with better value and outcomes.”

The rule change benefits companies like San Francisco-based Bone Health Technologies, which announced last month that its OsteoBoost Vibration Belt had received breakthrough device approval as a treatment for osteopenia, a precursor to osteoporosis.

“We are thrilled by this announcement as it will help us get our potentially life-changing device, affordably into the hands of patients who need it much more quickly,” said Laura Yecies, CEO of Bone Health Technologies. “There is a lack of safe, effective treatments for osteopenia, a condition that effects over 40 million Americans. It is exciting that CMS is supporting the efforts of companies working to solve these important unmet needs."

Another company likely to benefit is AppliedVR, which announced in October that its virtual reality headset had received breakthrough device approval as a treatment for fibromyalgia and chronic intractable low back pain.

“This new rule change means that Medicare recipients in need of pain relief will have access to our novel chronic pain therapy,” said Josh Sackman, co-founder and president of AppliedVR, who believes Medicare reimbursements will help speed up coverage of breakthrough devices by private insurers.  

“The MCIT rule change doesn’t directly impact coverage from commercial payers. They will continue to have their own standards for evidence and require new products to follow the existing evaluation process. However, the mandatory Medicare coverage will accelerate products getting into the market, where real world evidence will be collected on the value of those Breakthrough Devices,” Sackman explained in an email to PNN. 

“This data is extremely valuable for commercial payers to assess coverage. This should have a halo effect with payers that see the benefits of a breakthrough device in their Medicare book of business and may help them choose to expand coverage to their other lines of business, including commercial plans.”

Medicare coverage of a breakthrough device will initially be limited to four years. After the coverage period is over, CMS will reevaluate the devices based on clinical evidence of their effectiveness. Importantly, the four-year window also creates a revenue stream for manufacturers to continue improving their devices or invent new ones.

Skin Patch Reduces Pain Without Use of Drugs

By Pat Anson, PNN Editor

A drug-free skin patch that uses nanotechnology to help dial down pain levels provided significant relief to people living with arthritis, neuropathy and musculoskeletal pain, according to the results of a small study.

The Kailo pain patch contains billions of tiny nanoparticles made with copper, silver and silicon that help transmit electromagnetic signals from the nervous system. In theory, the nanoparticles act as a “bridge” over inflamed nerve pathways and restore their ability to transmit pain signals properly.

The patch is made by Utah-based Pain Relief Technologies, which claims in marketing material that its patented technology provides “natural relief anywhere on your body, in seconds.”

In the study, 66 patients wore the Kailo patch while continuing to take oral analgesic medications such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs).

After 30 days, self-reported pain levels dropped significantly and 98 percent of patients said they reduced or stopped using oral medication. Their mood, sleep, walking ability, and other quality of life measures also improved.

The study findings, published in the journal Anesthesia and Pain Research, suggest that the analgesic effects of the Kailo patch are long lasting. About one in every four patients said their pain did not return after the patch was removed. Over half said it took at least a day for the pain to resume.

CLARITY SCIENCE IMAGE

“Modern science has allowed the incorporation of nanotechnology into topical patch systems, minimizing, and in the case of Kailo, eliminating the need for drugs/pharmacological agents. The interim results of this study are incredibly positive, and we look forward to providing the next phase of data that we have collected from patients with mild, moderate or severe pain,” lead investigator Jeffrey Gudin, MD, said in a statement.

Gudin was compensated by Clarity Science for conducting the study. You may recognize him from TV commercials for SalonPas, a rival pain relief patch.

An anesthesiologist by training, Gudin has become a prolific researcher, consultant and public speaker for dozens of companies involved in pain management, including Purdue Pharma, Salix, BioDelivery Sciences and Quest Diagnostics. He’s been paid over $1.5 million for his services since 2013, according to the OpenPayments database. In an email to PNN, Gudin said most of the money has been used for research and consulting on new analgesic therapies.

The Kailo patch is reusable and can be purchased without a prescription for $119. Reviews on Amazon for Kailo are mixed.

“Immediately upon placing it on my low back I could feel a warmth and my pain decreased rapidly. I was able to go to work the next day with relative comfort,” wrote one buyer who suffered pain from a hamstring injury.

“Did not reduce pain actually increased pain level,” said a disappointed user.

“Nothing else has worked for me but this significantly reduced my pain. It does not completely remove the pain, so don't expect that. But it reduced it enough that I can play with my kids, mow the lawn, work, essentially be a normal human being without medication,” said another user.

“I used it for a week, received no relief whatsoever,” wrote another buyer. “I am very dissatisfied and would like my money back.”