Medical Cannabis Not Recommended for Chronic Pain in UK

By Pat Anson, PNN Editor

It was a little over a year ago that the UK’s Home Secretary announced that medical cannabis would be legalized in Britain and become available by prescription – a move that was cheered by cannabis activists.

“This is a major victory for our campaign and will mean a lot of people will have a much better quality of life,” said Clark French, a multiple sclerosis patient.

It turns out the celebration was premature. After a lengthy review, the UK’s National Institute for Health and Care Excellence (NICE) recently recommended to the National Health Service (NHS) that medications containing cannabidiol (CBD) only be used to treat epilepsy, multiple sclerosis and chemotherapy-induced nausea.

CBD was not recommended as a treatment for chronic pain, at least not yet.

“There is evidence to suggest that CBD reduces chronic pain,” NICE said. “However, where cannabis-based medicinal products reduced chronic pain, the benefit is small and economic analysis shows that this compares poorly with the high costs of (CBD products).”

Cannabis medications containing THC were also ruled out, even when combined with CBD.  Most cannabis products contain at least trace amounts of THC, the psychoactive ingredient in cannabis.

NICE said further research was needed to see if CBD can be used to treat fibromyalgia, neuropathy and cancer pain. It recommended that patients suffering from those conditions should only use CBD if they are part of a clinical trial.

One cannabis activist called the NICE guideline “a massive missed opportunity.”

“It is particularly devastating that there is no positive recommendation that the NHS should allow prescribing of whole-plant medical cannabis containing both CBD and THC in appropriate cases of intractable childhood epilepsy,” Millie Hinton, from the patient advocacy group End Our Pain, told The Guardian. “This restrictive guidance is condemning many patients to having to pay for life-transforming medicine privately, to go without, or to consider accessing illegal and unregulated sources.”

According to a recent survey, up to 1.4 million adults in the UK are self-medicating with illegal cannabis products.

The one big winner in the NICE report is GW Pharmaceuticals, the UK based company that developed Epidiolex and Sativex, two cannabis-based medicines that are used to treat childhood epilepsy and muscle spasms caused by multiple sclerosis. NICE had previously rejected Epidiolex because of its high cost, but is now recommending it.

“This is a momentous occasion for UK patients and families who have waited for so many years for rigorously tested, evidenced and regulatory approved cannabis-based medicines to be reimbursed by the NHS,” said Chris Tovey, GW’s Chief Operating Officer. “This is proof that cannabis-based medicines can successfully go through extensive randomised placebo-controlled trials and a rigorous NICE evaluation process to reach patients.”

Last year, the FDA approved the use of Epidiolex in the U.S. to treat seizures caused by two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The initial list price per patient was $32,500 a year.

Medical cannabis has been approved in 33 U.S. states and Washington DC, but the qualifying conditions vary from state to state. Click here for a list of qualifying conditions in each state.

FDA Approval Gives New Hope to Patients With Rare Genetic Disease

By Pat Anson, PNN Editor

Lisa Kehrberg was once frightened about her future. For years the retired family practice doctor and mother of two would suffer severe bouts of unexplained abdominal pain, headaches and nausea that would leave her hospitalized for weeks at a time.

“I was doubled over, rocking, vomiting and crying with the worst pain of my life. Worse than labor, appendicitis, or anything else I'd experienced. It was a hot, burning pressure that was like lava and hot razor blades filling up my abdomen,” Lisa recalled.

She was eventually diagnosed with a rare genetic disease called acute intermittent porphyria, which causes toxic molecules to build up in the body. The same disease killed Lisa’s brother in 2011. And she thought the same fate awaited her.

“One of the most common causes of death from porphyria is suicide. This isn't surprising. I always wonder how people who are sick like me keep surviving. To live in continuous excruciating pain every minute of every day with no end in sight is quite the challenge,” Lisa wrote in a 2016 column for PNN.

It was about that time that Lisa entered a clinical trial program. Every four weeks she’d travel to Houston from her home near Chicago for injections of an experimental drug. Over time, her symptoms began to improve and the porphyria attacks that used to occur monthly became less frequent.

LISA KEHRBERG, MD

Like other participants in clinical studies, Lisa wasn’t allowed to talk publicly about the drug she was getting – until now.  

The Food and Drug Administration has just approved the use of Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria (AHP). Approval was granted based on results from placebo controlled trials involving 94 porphyria patients. Those who received Givlaari experienced 70% fewer porphyria attacks compared to patients receiving a placebo.  

“Prior to getting givosiran I was bed-bound for close to 6 months straight from severe muscle weakness and paralysis issues. I no longer have paralysis and most of the muscle weakness has resolved,” Lisa said in an email. “The rate of new attacks has decreased greatly, finally giving my nerves a chance to heal after 22 years of attacks and 6 years of back-to-back attacks.”

“These attacks occur suddenly and can produce permanent neurological damage and death,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement Wednesday. “Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”

The FDA approved Givlaari under its breakthrough therapy, priority review and orphan drug designations, which provide incentives to companies in the development of drugs for rare diseases. Approval was granted to Alnylam Pharmaceuticals, which expects Givlaari to be available to healthcare providers by the end of the year.

There are about 3,000 people diagnosed with active porphyria in the U.S. and Europe. Due the wide array of symptoms the disease has, it can take years before an accurate diagnosis is made.

“The FDA approval of Givlaari is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director of the American Porphyria Foundation.

Image courtesy of Alnylam Pharmaceuticals

“AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of Givlaari is exciting for our community.”

Lisa Kehrberg isn’t out of the woods just yet. She has permanent nerve damage from years of porphyria attacks. But her future is a lot brighter than it was.  

“For newly diagnosed patients, I strongly believe this treatment has the ability to stop the progression of the disease and will allow patients to lead a normal, functional life,” she says. 

Biogen Accused of Price Gouging for New MS Drug

By Pat Anson, PNN Editor

FDA approval of a new multiple sclerosis (MS) drug has resulted in a big payoff for one company and sharp criticism from a patient advocacy group.

Last month the FDA approved Vumerity (diroximel fumarate) for the treatment of relapsing-remitting and secondary-progressive MS, as well as management of clinically isolated syndrome (CIS), neurologic symptoms that can be an early sign of MS — a chronic and progressive disease that attacks the body’s central nervous system.

Vumerity was jointly developed by Biogen and Alkermes. Under the terms of their operating agreement, FDA approval triggered a clause in which Biogen paid Alkermes $150 million for the worldwide commercial rights to Vulmerity, along with a share of future royalties.

Biogen said it would account for the Alkermes payment by amortizing its cost “over the expected useful life of the product.” It then announced the price of Vumerity – at a wholesale acquisition cost (WAC) in the U.S. of $88,000 per year. Biogen claimed that was “the lowest annual WAC price for oral MS disease-modifying therapies.”

MS drugs are notoriously expensive, but the $88,000 price tag for Vumerity brought a rare rebuke from the National Multiple Sclerosis Society, which released a statement that basically accused Biogen of price gouging.

“Vumerity is an efficacious and tolerable treatment option for people with relapsing MS, but being priced only $500 lower than the least expensive oral disease modifying treatment, does not show the commitment to affordable access that we had hoped,” said Bari Talente, executive vice president of advocacy for the National MS Society.

“We know that high wholesale acquisition cost (WAC) prices for MS disease modifying treatments put a heavy burden on people with MS. Too many are forced to take on high out-of-pocket costs, navigate through complex systems, and face varied and unpredictable decisions by public and private payers and pharmacy benefit managers.”

The statement points out Biogen has steadily escalated the price of another MS product, Tecfidera, by $40,000 since its launch in 2013. A year’s worth of treatment with Tecfidera now costs nearly $95,000.

“We urge Biogen to publicly commit to keeping price increases lower than the rate of inflation,” Talente said.

A recent study found that prices of several MS drugs have soared over the past decade, to an average of nearly $76,000 per patient annually.

“The pharmaceutical and biotechnology industries claim that the high prices reflect the expense of research and development and need to incentivize continued innovation. These claims are never backed up with transparent data,” said Daniel Hartung, PharmD, and Dennis Bourdette, MD, in an editorial in JAMA Neurology. “These drugs have long since recouped any cost of drug development, yet their prices have continued to rise.

“What is driving this increase is uncertain. However, the simplest explanation is that pharmaceutical and biotechnology companies increase prices because they can, they do it to increase their profit margins, and there are few limits on what they can charge.”

Biogen Involved in Illegal Co-Pay Charity

Biogen is one of three companies accused by federal prosecutors of paying a Florida-based charity to operate an illegal co-pay assistance program that helped Medicare patients buy high-priced MS drugs. The payments are considered kickbacks under a federal law that prohibits companies from subsidizing Medicare patients.

In a settlement announced Wednesday, The Assistance Fund (TAF) agreed to pay $4 million to resolve claims that it acted as a conduit for kickbacks from Biogen, Novartis and Teva Pharmaceuticals.

“Pharmaceutical companies and foundations cannot undermine the Medicare program through the use of kickbacks disguised as routine charitable donations. TAF operated as a vehicle for specific pharmaceutical companies to pay kickbacks at the ultimate expense of the American taxpayers who support the Medicare program,” said U.S. Attorney Andrew Lelling.

The DOJ has been cracking down on co-pay charities and the companies that fund them. Over $840 million in fines and penalties have been collected from eight pharmaceutical companies (United Therapeutics, Pfizer, Actelion, Jazz, Lundbeck, Alexion, Astellas and Amgen) to resolve allegations that they used third-party foundations to funnel kickbacks to patients.

Little Evidence to Support Rescheduling of Tramadol

By Roger Chriss, PNN Columnist

The consumer watchdog group Public Citizen has petitioned the FDA and DEA to “upschedule” the opioid painkiller tramadol. The DEA set tramadol as a Schedule IV drug in 2014, and the petition urges moving it to a more restrictive Schedule II, on the same risk level as hydrocodone and oxycodone.

The petition claims that tramadol is “an increasingly overprescribed, addictive, potentially deadly narcotic.” But the basis for this claim and the assumption that upscheduling will help are problematic.

The CDC reports that there were approximately 1,250 fatal overdoses involving tramadol in 2017, the most recent year for which data is available. Like most fatal overdoses, tramadol deaths often involve multiple drugs, so it’s hard to draw any conclusions from those deaths.

Tramadol is complex, with a highly variable patient response. Some patients have such a strong negative reaction to the drug that they refuse to take it again. Others find it too sedating at high doses or too weak to provide adequate pain relief. Abuse, addiction and overdose can also occur with tramadol.

Recently Harvard Health looked at a JAMA study on the risks of using tramadol versus other pain relievers. Tramadol was found to have a higher risk of death than anti-inflammatory medications such as naproxen (Aleve), while people treated with codeine had a similar level of risk.

“However, because of the study’s design, the researchers could not determine whether tramadol treatment actually caused the higher rates of death. In fact, the patients for whom tramadol is prescribed could make it look riskier than it truly is,” said Robert Shmerling, MD, an editor at Harvard Health.

Unintended Effects of Upscheduling

Understanding the effects of upscheduling is tricky. In 2014 the DEA reclassified hydrocodone (Vicodin) from Schedule III to the more restrictive Schedule II. The reclassification accelerated a trend that was already underway – hydrocodone prescriptions had been falling since 2011.

But there were unintended consequences to upscheduling. A recent University of Texas study found that decreases in hydrocodone prescribing after its rescheduling “were larger in patients being treated for cancer.”

Anotherr study found that upscheduling led to a substantial decrease in hydrocodone prescribing in hospital emergency departments, but that was offset by an increase in prescriptions for codeine and anti-inflammatory drugs.

Upscheduling hydrocodone has also had a negligible effect on overdoses, which are largely caused by illicit fentanyl, heroin and other street drugs, as well as non-opioid medications such as Xanax.

Similarly, predicting the impact of new prescription opioids is difficult. Breathless warnings about the opioid Zohydro, which was approved as a Schedule II drug in 2014, proved false. “There was no great surge of overdoses” after Zohydro was introduced, as Chris MacGreal wrote in his book “American Overdose.”

Fears about opioids are also delaying the introduction of safer medications. The experimental opioid NKTR-181 has less abuse potential than traditional opioids, but its approval is uncertain because the FDA has stopped all advisory committee meetings on opioid analgesics.

Public Citizen ignores all this. It also fails to mention other actions the FDA could pursue, from making naloxone into an over-the-counter drug to improving access to medication-assisted therapy for opioid use disorder. There’s no petition to have the DEA “nix the wavier” for buprenorphine (Suboxone) to make it more widely available or to have the federal government promote the Pain Management Best Practices Inter-Agency Task Force report.

Finally, there’s no call to monitor outcomes. As PNN has reported, opioid tapering has had tragic unintended consequences. And a new Cochrane review on the effects of educational and regulatory efforts targeting prescribers was unable to draw any conclusions “because the evidence is of very low certainty.” The authors could find only two relevant studies that assessed prescribing policies adopted in the 1990’s.

There are good reasons to be cautious about tramadol. But there are probably better ways than upscheduling to reduce risks and improve outcomes. As a result, Public Citizen's petition seems quite narrow and unlikely to help with the overdose crisis.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Experts Warn Rx Opioids Being Denied to Breast Cancer Patients

By Pat Anson, PNN Editor

Patients with advanced breast cancer are being denied opioid pain medication due to lack of supply in poor countries and a backlash against opioid addiction in the United States, according to experts at an international conference on breast cancer recently held in Lisbon.

In a session agreeing to new guidelines for treating breast cancer, oncology experts at the Advanced Breast Cancer Fifth International Consensus Conference also called for better access to a group of anti-cancer drugs called CDK4/6 inhibitors. The drugs help breast cancer patients live longer and improve their quality of life, but are often not available.  

The guidelines also warn that cancer patients should not have limits placed on their access to adequate pain control.

“Patients with advanced breast cancer can suffer pain and other symptoms, particularly towards the end of their lives. We need to ensure that appropriate pain medications and other symptom interventions are available to them,” said conference co-chair Eric Winer, MD, Director of Breast Cancer Program at Dana-Farber/Harvard Cancer Center in Boston.

“We acknowledge that the misuse of opioids is a big problem, particularly in the United States, but we need to make sure that in trying to deal with this problem we do not interfere with pain management in cancer patients. In addition, in some low- and middle-income countries, such as some in Africa, there are problems with patients being able to access any form of pain relief, and this needs to be addressed urgently.”

The panel of experts also called for more research into the use of cannabis for managing pain and other symptoms in patients with advanced breast cancer. But they cautioned that cannabis should not replace pain relievers that have been proven to work.

“The panel encourages research on the potential role of cannabis to assist in pain and symptom control but strongly stresses that it cannot replace proven medicines, such as morphine, for adequate pain control,” the guideline state.

Over two million new cases of breast cancer are diagnosed worldwide ever year, and there are about 600,000 deaths annually from the disease.

Confusion Over CDC Guideline

Although the CDC’s 2016 opioid guideline is only intended for primary care physicians treating non-cancer pain, the recommendations include patients “who have completed cancer treatment, are in clinical remission, and are under cancer surveillance only.”  

Experts say the CDC’s inclusion of cancer survivors is a mistake because it is not uncommon for cancer pain to persist long after the cancer is treated.  The CDC’s recommendations also conflict with cancer treatment guidelines that suggest doctors use both short and long-acting opioids when treating flares from cancer pain. The CDC recommends against long-acting opioids because of the potential risk of addiction.

The conflicting recommendations have caused confusion for oncologists and pharmacists, and agony for cancer patients not getting proper pain relief.

Earlier this year, a Rite Aid pharmacist refused to fill an opioid prescription for a California woman with Stage 4 terminal breast cancer.  April Doyle posted a tearful video online about her experience at the pharmacy that went viral. The pharmacist and a Rite Aid manager later apologized to Doyle for the incident.  

Rx Drug Databases Linked to Heroin Deaths

By Pat Anson, PNN Editor

Prescription drug monitoring programs (PDMPs) in the U.S. are often promoted as critical tools in preventing opioid abuse and addiction. But a new study suggests that some PDMPs may be having the unintended effect of driving pain patients to street drugs such as heroin.

PDMPs in 49 states (the one exception is Missouri) allow physicians and pharmacists to consult a drug database to see if patients are “doctor shopping” or getting too many opioid prescriptions. The databases are also used by law enforcement agencies to identify doctors who prescribe high levels of opioid medication.  

A team of researchers reported in the International Journal of Drug Policy that there was a “consistent, positive, and significant association” between the adoption of PDMPs and fatal heroin overdoses. By the third year of a state adopting a PDMP, there was a 22% overall increase in heroin fatalities.

The increase was not uniform across all PDMPs.  States with “Proactive” PDMPs, which are more likely to flag suspicious activity by doctors and patients and report them to law enforcement, had a slight decline in heroin overdoses, while states with weaker PDMPs had significant increases in heroin deaths.

“The study just shows that heroin is an alternative to prescription pain medicine,” says John Lilly, DO, a Missouri physician who opposes PDMPs. “The harder it is to get prescription pain medicine, the more heroin deaths and presumably heroin use occurs. Market forces at work. Heroin is not the big alternative. It’s illicit fentanyl.”

It's not the first time researchers have found mixed results on the effectiveness of PDMPs. A 2018 study also found an increase in heroin deaths associated with PDMPs, along with a decline in overdoses linked to prescription opioids.

"It's pretty striking that this is the second study where we have found that PDMPs with robust features such as sending unsolicited alerts about outlying prescribing and dispensing patterns to PDMP users, and providing more open access to PDMP data, are associated with a small decline in opioid overdose deaths," said senior author Magdalena Cerdá, DrPH, an associate professor and director of the Center for Opioid Epidemiology and Policy at NYU Langone Health.

"In our prior study we found that these types of PDMPs were associated with a decline in prescription opioid overdose deaths, and this new study suggests Proactive PDMPs may also have a downstream protective effect on heroin overdose risk."

Cerdá and her colleagues believe PDMPs that aggressively flag and report suspicious activity will help stop inappropriate prescribing sooner and better identify patients in need of addiction treatment, preventing their transition to heroin. 

“To the best of our knowledge, this study is the first to identify specific classes of PDMP characteristics that are most strongly associated with changes in rates of fatal heroin poisonings,” said lead author Silvia Martins, MD, an associate professor of epidemiology at Columbia Mailman School of Public Health. “We believe those authorized to access the data should be trained to protect individual privacy and confidentiality and ensure that it is used only to improve care for the patient.”

DEA Sues Colorado for Access to PDMP

Patient privacy is at issue in an unusual lawsuit filed last week by the Drug Enforcement Administration against Colorado’s Board of Pharmacy. The DEA subpoenaed the board to release patient data from Colorado’s PDMP to assist in the investigation of two pharmacies. But the state refused to comply, citing privacy concerns.

“The Department of Regulatory Agencies is committed to combating the opioid epidemic that remains a devastating issue for many Colorado communities,” spokeswoman Jillian Sarmo said in an email to the Colorado Sun. “We continue to work with our partners in other agencies in this fight, but we have an obligation to do so in a targeted and thoughtful manner that ensures the privacy of the hundreds of thousands of individual patients in the state whose personal prescription records have no connection to any criminal activity and whose disclosure has no relevance to any criminal investigation.”

Also named in the DEA lawsuit is Appriss, Inc., a private company that Colorado and dozens of other states use to collect and maintain their PDMP data. If a federal judge rules in favor of the DEA in Colorado, it could set a legal precedent that would force Appriss to release prescription data from other states.

“We are taking this action as part of our office’s efforts to aggressively pursue law enforcement investigations of anyone who may be breaking the law,” U.S. Attorney Jason Dunn said in a statement.  “We are disappointed with the refusal to comply with these lawful subpoenas, a refusal that has forced us to seek aid from the court in getting the information we need to carry out important law enforcement investigations aimed at combating the prescription drug abuse epidemic.” 

A recent study undermines much of the association between overdoses and prescription opioids that are obtained legally. Researchers say only 1.3% of overdose victims in Massachusetts had an active prescription for the opioid that killed them — meaning PDMPs would have little value in preventing the other 98.7% of deaths.

Patients on Rx Opioids Often Tapered at Risky Levels

By Pat Anson, PNN Editor

Tens of thousands of pain patients on long term opioid therapy have been cutoff or tapered to lower doses more rapidly than recommended, putting them at risk of withdrawal, uncontrolled pain and suicide, according to a large new study.

The study, published in JAMA Network Open, is one of the first to assess the impact of the 2016 CDC opioid guideline and other measures aimed at reducing opioid prescribing.

Researchers at University of California Davis reviewed the prescription records of over 100,000 patients on stable opioid doses from 2008 to 2017.

The percentage of patients who were tapered rose significantly during the study period -- from 10.5% in 2008 to 22.4% in 2017 – especially for patients on relatively high daily doses that exceeded 90 MME (morphine milligram equivalent).

“Opioid tapering has become increasingly common among patients using long-term opioids, particularly among patients taking higher doses and since the publication of the CDC opioid prescribing guideline,” researchers found.   

SOURCE: JAMA NETWORK OPEN

“Our results also suggest that many patients undergo tapering at rapid maximum rates. The downstream effects of opioid tapering on pain, withdrawal, mental health, and overdose risk warrant careful evaluation.”

Federal guidelines recommend a gradual dose reduction of about 10% per month. But researchers found that tapering for nearly one in five patients exceeded that level and some were tapered at rates six times higher than recommended. The average dose reduction overall was 27.6% per month.

"Tapering plans should be based on the needs and histories of each patient and adjusted as needed to avoid adverse outcomes," said study author Alicia Agnoli, MD, an assistant professor of family and community medicine at UC Davis. “Unfortunately, a lot of tapering occurs due to policy pressures and a rush to get doses below a specific and sometimes arbitrary threshold. That approach can be detrimental in the long run."

Too rapid tapering can have devastating consequences on patients and their families. Such was the case for Bryan Spece, a 54-year old Montana man who committed suicide after his dose of oxycodone was abruptly reduced by 70 percent. The pain clinic that tapered Spece said it was following the CDC guideline.

"He was the last person anyone would have thought to take his own life. He was just not that guy," a family member told PNN. "I know he was in a lot of pain and in a very dark spot."

Women More Likely to Be Tapered

Although men are twice as likely as women to die from an opioid overdose, UC Davis researchers found that tapering rates for women were about 13% higher than men, which they attribute to a possible sex bias.

“When considering dose tapering for patients, clinicians may fear that a recommendation of tapering may prompt angry or even violent responses, particularly from male patients. Such perceptions may be associated with a sex bias among clinicians, manifesting as a greater willingness to initiate tapering among women than men,” researchers said.

Although patients who survive an opioid overdose are at substantial risk of overdosing again, the study found that less than one in four patients (23.4%) with recent overdoses were tapered by their prescribers.

Researchers hope to build on the study further to develop best practices for dose reduction.

"Ultimately, we want to clarify the effects of tapering on patients and how to help them taper to maximize benefits and minimize risks," said lead author Joshua Fenton, MD, a professor of family and community medicine at UC Davis. "We expect this line of research will have important implications for how physicians manage and monitor patients who are undergoing opioid tapering."

The Food and Drug Administration first warned in April that many pain patients were being tapered inappropriately, putting them at risk of serious harm. That was followed a few days later by a pledge from CDC Director Robert Redfield, MD, to evaluate the impact of the agency’s opioid guideline and to “clarify its recommendations.”

Seven months later, not a single word of the CDC guideline has been changed or clarified. Outside of an editorial published in the New England Journal of Medicine, the CDC has made no effort to publicize or widely disseminate warnings to doctors not to taper patients too rapidly.

Not until last month – three and a half years after the CDC guideline was released – did the Department of Health and Human Services publish a 6-page guide for doctors on how to taper patients. The guide encourages prescribers to collaborate with patients and “obtain patient buy-in” before starting a tapering program.

EPA Decision Will Stifle Animal Research on New Pain Treatments

By Dr. Lynn Webster, PNN Columnist

People in pain rely on scientific advances to find safer, more effective alternatives to opioids. Animal research is key to many of our advances in drug development.

But a recent announcement from the Environmental Protection Agency threatens to change that -- by inhibiting science’s ability to replace opioids and create new life-saving pain interventions.

EPA administrator Andrew Wheeler announced in September the agency's decision to "significantly curtail its reliance on the use of mammals in toxicological studies conducted to determine whether environmental contaminants have an adverse impact on human health."

The EPA plans to reduce funding for most mammal studies by 30% by 2025 and eliminate them altogether by 2035.

The agency also announced that five universities would receive $4.25 million in federal funding to develop alternatives to reduce or replace the use of animals in research.

Ostensibly, Wheeler worries about the potential mistreatment of animals used in testing. But Natural Resources Defense Council (NRDC) scientist Jennifer Sass believes he may be politically motivated.

“The Trump administration appears to be working on behalf of the chemical industry and not the public,” Sass said in an NPR interview.

Most likely, the American Chemistry Council, which represents chemical companies, would prefer to eliminate mammal studies that could prove the toxicity of their products. Wheeler, however, claims he hasn't talked to "a single chemical company about this."

According to The New York Times, the American Lung Association, the American Heart Association, and the American Medical Association disagree with Wheeler's strategy. Lab-grown cells and computer modeling can reduce the need for animal testing. But Penelope Fenner-Crisp, a former senior official at the EPA, believes 2035 may be too soon to ban all animal studies.  

"There's currently no substitute for [testing] some of the more complex and sophisticated toxicities, such as the effect of chemicals on animals' reproductive systems," she said.

The NRDC, an environmental advocacy group, also opposes the EPA's plan to ban animal testing on the grounds that it could make it harder to identify toxic chemicals and protect human health.

Animal research has played a key role in developing many new technologies, including MRIs, ultrasounds, CT scans, and new surgical techniques. It has also played an integral role in the development of vaccines, pain relievers and other medications, as well as life-saving emergency care.

“Virtually everything a doctor, nurse, veterinarian, veterinary technician, paramedic, or pharmacist can give the injured or sick was made possible by animal research," says Dr. Henry Friedman, a neuro-oncologist who leads the opposition to the EPA decision.

Dr. Friedman says sophisticated computers can be helpful in many areas of scientific research, but they "can't predict everything a new drug will do once inside you." He also maintains that laboratory animals are treated humanely under strict guidelines.

Speaking of Research, an international advocacy group that supports the use of animal research, believes the EPA's plan endangers human, animal and environmental health.

"This directive flies in the face of the EPA’s mission to 'protect human health and the environment' and 'to ensure that national efforts to reduce environmental risks are based on the best available scientific information.' Animal-based research and testing is critical for understanding how new chemicals and environmental substances affect human and non-human animals," the organization said in a statement.

Many of us in the scientific community oppose the EPA’s decision because it could slow drug development and threaten our ability to find safer and more effective treatments for pain, addiction and other diseases. If the EPA decision is sustained, it will be a major obstacle to the advancement of medical science.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is the author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences or Pain News Network.

Chronic Pain Often Leads to Frailty in Older Mexican Americans

By Pat Anson, PNN Editor

A new study has found that leaving chronic pain untreated or poorly treated can have serious health consequences for senior citizens. Older Mexican Americans who suffer from pain are 1.7 times more likely to become frail, according to findings published in the Journal of Pain.

Frailty is characterized by unintentional weight loss, weakness, exhaustion or slowness in older adults. Chronic pain is a risk factor for frailty in all older adults, but not enough is known about the relationship between pain and frailty in older Latino populations, the fastest growing segment of older adults in the United States.

To learn more about it, researchers at the University of Texas Medical Branch, Galveston, followed over 3,000 Mexican Americans aged 65 or older. Data was collected from 1995 to 2013.

At the start of the study, participants were asked if they experienced pain in the previous month. Social, health and demographic data were also collected, such as age, sex, marital status, literacy, mental health, disability and medical conditions. Those categorized as frail were not included in the study.

Eighteen years later, 41 percent of the participants who reported pain were considered frail. Old age, hip fractures, depression and disability were also associated with higher odds of becoming frail.

Researchers say older Mexican Americans are particularly prone to frailty because they often have poor access to medical care. They are also nearly twice as likely as non-Hispanic whites to suffer from type 2 diabetes, a leading cause of peripheral neuropathy.

“Older Mexican Americans are an underserved population with disparities in healthcare access and delivery and health risks associated to their demographic group,” said Eliseo Pérez-Stable, MD, Director of the National Institute on Minority Health and Health Disparities. “This study identifies the need to effectively manage pain in Latino populations by culturally appropriate interventions.”

Women in the study who had higher levels of education or higher mental agility scores were found to have less risk of becoming frail.

“The relationship between social determinants, diabetes, physical function, mobility, frailty and pain in older Mexican Americans is complex and poorly understood,” said Kenneth Ottenbacher, PhD, the study’s principal investigator. “Early assessment and better pain management may prevent early onset of frailty in this group.”

The study was funded by the National Institutes of Health.

How to Control Anxiety and Pain Through Meditation

By Dr. David Hanscom, PNN Columnist

Every sense in your body has a threshold that indicates danger – hot, cold, bitter, loud, bright, sharp, pressure, burning, nausea, etc. Without that immediate feedback from your senses, you could not protect yourself from whatever the danger is.   

When any physical threat is sensed, your body secretes chemicals and hormones to increase your chances of survival. They include cortisol, adrenaline and histamines. This chemical bath affects every cell in your body and you are on “high alert.” The feeling generated is anxiety and it is not a psychological reaction. 

Humans have a problem in that mental threats manifested by unpleasant thoughts are processed in similar area of the brain and cause the same hormonal response. But since we can’t escape our thoughts, we are subjected to sustained levels of these chemicals. One of the effects is increasing the speed of nerve conduction. All of our senses are heightened, including various types of pain.  

Environmental Awareness 

Being aware of your senses – known as environmental awareness –-- is a strategy that allows you to switch sensory input from racing thoughts to another sensation. It doesn’t matter which sense you choose.

I practice one that I call “active meditation” or “meditation on the run.” Being aware of your senses has a calming effect on your nervous system. Active meditation enabled me to be a calmer person and more effective in my work.  

As a retired spine surgeon with many years of experience, I was often referred complicated spine problems that required complex surgeries. Sometimes those surgeries resulted in complications for the patient. Although I was committed to having no complications from the first day I walked into the operating room, there was a point a few years ago when I faced up to the fact that I hadn’t been able to eliminate them. My own thoughts were interfering with my work.  

The most common interferences I felt during surgery were frustration, anxiety, distraction, complacency, and, especially, being in a rush to finish. They all detracted from the consistency of my performance. This led me to develop a somewhat defensive mindset. If I could get through the week without a surgical complication, it was a huge relief.  

Learning Active Meditation

Things changed when I decided to enlist the help of a performance coach to help me reduce any mistakes in surgery. That was a major turning point in my professional life. I brought my coach into the operating room and clinic so he could better understand my world. For 18 months, he and I underwent regular debriefings and coaching. I began to use active meditation in the operating room. 

This meditation model is not based on suppressing interference – for instance, if you’re frustrated, you don’t pretend otherwise – rather, you face these frustrations and then detach from them. Using tools and approaches that have been employed for centuries in the practices of meditation and mindfulness, I learned to identify any interference either before or during surgery, and then let go of it.  

This is how it worked: Each surgical morning, I woke up and assessed how I was feeling. Like everyone, my feelings ranged from calm and relaxed to tired and anxious. Then, I immediately started sensing every smell, touch and taste possible. I felt the water on my back in the shower. I smelled the coffee. I also reminded myself that although that day’s surgery is “just another case” for me, it’s one of the most important days of my patient’s life.  

I continued this process in the operating room. I carefully arranged the room, talked to each member of the surgical team, and reviewed the imaging studies. I was focused and immersed in what’s right in front of me, when previously I’d rush into the operating room at the last minute just before making the incision. 

During surgery, awareness allowed me to perform my next move at an optimum level. I felt my grip pressure on each surgical tool; noticed the shape of the contours of the anatomy; felt my shoulder and arm muscles stay relaxed; and just watched the flow of the case.  

If I felt any disruptive emotions intrude into my state of mind, I quickly practiced my environmental awareness techniques in order to re-focus. I learned to be more fully engaged on a higher percent of cases, so I could “program” myself into the “zone.” 

Since I started practicing active meditation, my complication rate in surgery noticeably decreased. For instance, from 1999 until 2003 I had an “acceptable” 9% rate of inadvertently entering the dural sac (a sack of fluid surrounding the brain and spinal cord). After I started using meditation, I made this mistake only two or three times a year, which is less than one percent. 

Surgery became a wonderful experience for me. I eagerly looked forward to Monday instead of Friday. I committed to getting a good night’s sleep before my surgeries.  If I woke up “wired” and uneasy, I slowed down until I felt relaxed, no matter how many things were on my to-do list.  

I continue to practice active meditation daily. Environmental awareness is more difficult outside the operating room, in the less controlled areas of my life, but it is still my go-to active meditation.   

One tool I use to practice awareness is my “to do” list. I remind myself that this list is an expression of my life, and so I practice being aware as I go about each item. For instance, when I have an appointment with a patient, I listen to myself talk to him or her.  I feel the pen on the paper as I jot down notes.  I also practice meditative techniques. such as watching the disruptive thoughts of “need to finish up here, I have other things to do” enter my consciousness and then leave.  

I remember that my goal is to engage and enjoy every second of my “to do” list. It doesn’t always work, but it’s surprising how often it does.

Environmental awareness engages me in the present moment regardless of the circumstances. It is not positive thinking, but just switching the sensory input. With repetition, it has become somewhat automatic. It is a simple strategy that can help the quality of your life, regardless of the level of your pain.  

Dr. David Hanscom is a retired spinal surgeon who has helped hundreds of back pain sufferers by teaching them how to calm their central nervous systems without the use of drugs or surgery.

In his latest book, Do You Need Spine Surgery?, David explains why spinal surgeries are often risky and unnecessary.

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Petition Urges DEA to Reschedule Tramadol

By Pat Anson, PNN Editor

In 2014, the U.S. Drug Enforcement Administration reclassified the opioid hydrocodone as a Schedule II controlled substance, citing evidence that the painkiller has a high potential for abuse and addiction. The change made it harder to obtain the drug and led to a sharp decline in hydrocodone prescriptions.

That same year, the opioid tramadol was classified for the first time as a Schedule IV drug – a less restrictive category that means it has low potential for abuse and addiction. Prescriptions for tramadol surged.

Five years later, a consumer watchdog group is saying that was a mistake. Public Citizen has filed a petition with the FDA and DEA asking that tramadol be reclassified as a Schedule II drug, on the same risk level as hydrocodone, oxycodone, morphine and fentanyl. The petition claims there is “overwhelming evidence” that tramadol is a public health risk, particularly for people who rapidly metabolize the drug.

“New evidence has accumulated showing that tramadol is an increasingly overprescribed, addictive, potentially deadly narcotic that should be rescheduled to Schedule II,” the petition states. “Tramadol’s current placement in Schedule IV has generated a false perception of the drug’s safety profile — particularly with respect to its potential for abuse, dependence, and addiction — among both prescribers and patients, which has contributed to the large increase in its prescribing following the DEA’s 2014 rescheduling of hydrocodone.”

Tramadol is considered a “weak” opioid because it does not bind directly to opioid receptors in the brain like hydrocodone and other opioids do. Many patients say tramadol gives them little or no pain relief, but it’s often the only opioid their doctor is willing to prescribe.

Tramadol is the active ingredient in several brand name painkillers such as Ultram, Ultracet, Ryzolt and Rybix. About 32 million prescriptions for tramadol were filled last year in the U.S.

“The failure to designate tramadol as a controlled substance when it was initially approved by the FDA and the subsequent placement of the drug in a less restrictive category has promoted the false belief that the drug must have a much better safety profile than other opioids,” Dr. Michael Carome, director of Public Citizen’s Health Research Group, said in a statement.

“The dangerous misperception of tramadol’s safety has led to reckless overprescribing of the drug during the past several years of the opioid epidemic.”

According to government health surveys, tramadol was misused by about 1.5 million people in 2018 – exceeding the number of people that misused morphine and some other Schedule II opioids.

In 2017, the FDA banned the use of tramadol in children under the age of 12, citing a handful of cases where children died or had serious breathing problems after using the drug.

A recent study by the Mayo Clinic found that patients given tramadol after surgery have a slightly higher risk of prolonged use than those receiving oxycodone or other short acting opioids.

Tramadol was classified as a Schedule 3 drug in the United Kingdom in 2014. It is still an unscheduled drug in Canada, although Health Canada has proposed classifying it as a Schedule I controlled drug.

Tramadol is widely abused in West, Central and North Africa.

CDC Guideline Author Leading New Rx Opioid Study

By Pat Anson, PNN Editor

One of the co-authors of the CDC’s controversial 2016 opioid guideline is leading a new federal study about the effectiveness of opioid medication in treating chronic pain, Pain News Network has learned. 

Dr. Roger Chou is a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University (OHSU), which was awarded a $500,000 contract to conduct the opioid study by the federal Agency for Healthcare Research and Quality (AHRQ).   

A draft version of the AHRQ report echoes many of the conclusions drawn by the CDC – that there is little evidence to support the use of opioids for chronic pain and that nonopioid pain relievers such as Tylenol are just as effective as Vicodin.

Even when used for short-term acute pain, the draft report found “no differences between opioids versus nonopioid medications in improvement in pain function, mental health status, sleep, or depression.”

The AHRQ has not publicly disclosed the authors of the draft report, and only acknowledged in a statement to PNN that “the OHSU team is comprised of several experts who draw upon diverse experience and expertise in pain management.” Their final report is expected in January 2020.

In addition to his work on the CDC guideline, Chou has authored numerous articles on pain management in peer-reviewed medical journals and has led research efforts for the U.S. Preventive Services Task Force, World Health Organization and the American Pain Society. But Chou’s involvement in the AHRQ study has caused some alarm among patient advocates, who believe he and the agency are biased against prescription opioids.

“The agency is operating under a political agenda that has little to do with medical evidence or truth,” said Richard “Red” Lawhern, PhD, a patient advocate with the Alliance for the Treatment of Intractable Pain. “The report is fatally flawed and must be immediately withdrawn without replacement. AHRQ owes the public and millions of people in pain a public apology for its malfeasance and misdirection.”

PROP Collaboration

Most health researchers keep a low profile and try to avoid controversy, but Chou has publicly collaborated with Physicians for Responsible Opioid Prescribing (PROP), an influential anti-opioid activist group that seeks drastic reductions in the use of opioid medication.

Chou recently co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

Chou and his co-authors thanked PROP Executive Director Dr. Andrew Kolodny and other PROP board members for their help in drafting the article:

“Acknowledgment: The authors thank the Oregon Pain Guidance Working Group (Jane Ballantyne, Roger Chou, Paul Coelho, Ruben Halperin, Andrew Kolodny, Anna Lembke, Jim Shames, Mark Stephens, and David Tauben) for discussions about tapering and for reviewing a draft of this article.”

As PNN has reported, Kolodny, Ballantyne and Lembke have worked as paid consultants to law firms that stand to make billions of dollars from opioid litigation. Their legal work was only recently disclosed in revised conflict of interest statements.

It is not clear if PROP members are involved in the AHRQ study, as they were with the CDC guideline. As a matter of policy, AHRQ does not disclose the names of its consultants and investigators until after reports are completed.

“This policy is aimed at helping the authors maintain their independence by not being subject to lobbying by industry reps or others with conflicts of interest, either financial or intellectual,” AHRQ spokesman Bruce Seeman said in an email.

“AHRQ’s failure to disclose Chou as an author of its draft report is troubling, given his prior work with Ballantyne and Lembke, who have admittedly worked on behalf of PROP in the past.”

— Dr. Chad Kollas

“AHRQ’s failure to disclose Chou as an author of its draft report is troubling, given his prior work with Ballantyne and Lembke, who have admittedly worked on behalf of PROP in the past. PROP heavily influenced the creation and implementation of the 2016 CDC Guideline, which was systematically misapplied over the last three years by lawmakers, health insurers and pharmacies in a way that became harmful to many patients with chronic pain,” said Dr. Chad Kollas, a palliative care specialist in Florida.

“Failing to disclose authorship of the AHRQ report reduces the agency’s transparency in a way that raises alarms for those familiar with the misapplication of the CDC Guideline and seek to prevent recurrent harm to patients suffering from chronic pain.”

Chou did not respond to requests for comment for this story. He recently served on a state task force that recommended a rigid tapering policy that would have forced many Oregon Medicaid patients off opioids and into withdrawal. The policy was scaled back after a backlash from patients and pain management experts, who said the recommendations were not supported by evidence or compassionate.  

“Compassionate sounds good but it’s a loaded term,” was Chou’s response at the time. “I don’t think there’s anything compassionate about leaving people on drugs that could potentially harm them.”

On a recent podcast, Chou said there was little of evidence to support the use of opioid medication.

DR. ROGER CHOU

“The impact of prescription opioids in terms of mortality and substance use disorder and all the other things that come along with it have really been quite staggering.  We have more evidence that the benefits of opioids are really not as large as we’d like them to be. In most studies, they’re actually quite small and often clinically insignificant,” he said.

Chou also claimed in the May 2019 interview that the opioid hydrocodone was “the number one prescribed drug in the United States and has been for many years.” That statement is false. Since 2011, hydrocodone prescriptions have fallen dramatically – as they have for all opioids -- and it is now the fifth most widely prescribed drug in the U.S., ranking behind cholesterol, thyroid and blood pressure medications.

Public Comment Period Ends

On Tuesday, the AHRQ ended a 30-day public comment period on its draft report. Unlike other federal agencies that routinely seek public comments in the Federal Register, the AHRQ only accepted comments on its website. The agency did little to publicize the draft report outside of a mass email to 100,000 subscribers notifying them the report was available for comment. 

One critic who had a chance to see the AHRQ’s review of over 150 opioid studies said it was filled with errors, biases and cherrypicked research – much like the CDC guideline that Chou co-authored.

“In laymen’s terms, AHRQ and CDC have been caught with their fingers on the balance scales, in a deliberate and unconscionable effort to bias public policy against the use of opioid therapies regardless of the medical evidence,” Lawhern said in a written public comment.  “CDC violated its own research standards by failing to explicitly acknowledge that the medical evidence for alternatives to opioids is no stronger than for opioids. Now AHRQ proposes to compound that lack of public transparency by doubling down on a false narrative.”

Although voluntary, the CDC’s dose recommendations have been widely misapplied by insurers, pharmacies, doctors, and federal and state regulators – who have adopted the guideline as policy or even law — and used it as an excuse to abruptly cutoff or taper patients on opioids.

“We are concerned that the AHRQ review may have similar unintended consequences,” the American Medical Association said in a letter to the agency. The letter points out that most opioid overdose deaths are caused by illicit fentanyl and other street drugs, not prescription opioids.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report... to help remove any perception of potential conflict.”

— Dr. James Madara, AMA

“The AMA urges the AHRQ to clarify that the review does not support a conclusion that the epidemic of opioid-related overdose deaths is due to efforts to treat patients with chronic pain or cancer pain, or to manage pain for patients receiving hospice or palliative care,” said Dr. James Madara, the AMA’s Executive Director and CEO. “The AMA further urges the AHRQ to clarify that this review should not be used to justify or support reductions in opioid therapy for patients with acute, chronic, palliative, cancer-related or other pain when clinically indicated by the patient’s physician.”

The AMA’s letter also urged the AHRQ to publicly identity everyone the agency consulted with before its final report is released.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report during the comment period to help remove any perception of potential conflict,” Madara wrote.

PROP President Discloses Conflicts of Interest

By Pat Anson, PNN Editor

The president of Physicians for Responsible Opioid Prescribing (PROP) – an influential anti-opioid activist group – has worked as a paid consultant for the national law firm of Motley Rice, which stands to make billions of dollars in contingency fees from opioid litigation.

Dr. Jane Ballantyne disclosed her work with Motley Rice in a revised disclosure statement recently made public by the Annals of Internal Medicine, a prominent medical journal. Ballantyne co-authored an op/ed in the journal in September that called for “every patient receiving long-term opioid therapy” to be assessed by doctors for tapering off the drugs.

In her original conflicts of interest statement, Ballantyne did not disclose her work for Motley Rice, her affiliation with PROP or any other conflicts. 

“In a recent Ideas and Opinions commentary, Dr. Ballantyne did not disclose that she has received personal fees for the multidistrict opioid litigation because her consultancy in the litigation was under a confidentiality agreement. Dr. Ballantyne has now updated her disclosure because her role in the multidistrict litigation has since become public knowledge,” the medical journal said in a statement.

Ballantyne did not disclose the amount of compensation she received from Motley Rice.

Dr. Anna Lembke, a Stanford psychiatrist who co-authored the Annals article, said in her initial disclosure statement that she was also a paid expert witness in opioid litigation, but did not reveal what law firm she works for. In a new statement, Lembke discloses that she is a PROP board member.

“In the spirit of full transparency, Drs. Ballantyne and Lembke have decided to disclose their involvement in Physicians for Responsible Opioid Prescribing (PROP) as well. PROP is a 501c3 charitable organization. Their roles are volunteer positions without financial remuneration,” the journal said.

The claim that PROP is a 501c3 non-profit organization is puzzling because PROP is not a registered charity with the Internal Revenue Service. Instead it uses the Steve Rummler Hope Network as its "fiscal sponsor" -- an IRS designation that allows PROP to piggyback onto another organization’s 501c3 status. Because it is not a charity, PROP has never filed a federal or state tax return and is not required to disclose anything about its revenue, donations or spending.

Ballantyne and Lembke are not the first PROP members to revise their financial disclosure statements or to work as paid consultants in opioid litigation. PROP founder and Executive Director Dr. Andrew Kolodny recently revised his conflict of interest statements for the Journal of the American Medical Association (JAMA) to include his work in opioid malpractice lawsuits.  

DR. JANE BALLANTYNE

Ballantyne, a retired anesthesiologist and professor at the University of Washington School of Medicine, is a controversial figure in the pain community because of her role in drafting the CDC’s controversial 2016 opioid prescribing guideline. Many blame the guideline for a surge in suicides by patients who were abandoned by their doctors or forcibly taken off opioids.

Although Ballantyne was known to have strong negative opinions about prescription opioids and worked in the past as a paid consultant for Cohen Milstein Sellers & Toll  -- another law firm involved in opioid litigation – she was still allowed to serve on the “Core Expert Group” that advised the CDC when it drafted the guideline. Several other PROP members also served as advisors to the CDC, which the agency did not disclose until it was threatened with a lawsuit.

Lucrative Sideline

As PNN has reported, working as a paid consultant or expert witness has become a lucrative sideline for Kolodny and other anti-opioid activists. The lawyers that hire them are eager to have them testify in opioid litigation cases that will likely reward their law firms with billions of dollars in contingency fees.  

Kolodny recently testified as the “star witness” for Oklahoma in its opioid negligence lawsuit against Johnson & Johnson. For that, he was paid $725 an hour by Nix Patterson & Roach, one of three law firms hired by Oklahoma to handle the case against J&J. Kolodny, who stands to make up to $500,000 for his testimony in the Oklahoma case, also acknowledged working as a consultant for Cohen Milstein at a rate of $725 an hour.

Cohen Milstein and Motley Rice are lead counsels in a national opioid litigation case in Cleveland that has consolidated about 2,600 lawsuits filed by states, cities and counties against opioid manufacturers and distributors. According to Legal NewsLine, the law firms could take home 40% of any settlements, which are projected to reach about $50 billion.

“The firm that stands to win the most will likely be Motley Rice, which pioneered the strategy of joining forces with government attorneys to sue the tobacco industry in the 1990s. Motley Rice name partner Joe Rice has never revealed his personal take from the $260 billion tobacco deal but private lawyers in total will receive $14 billion from the multi-year agreement,” Legal Newsline reported.   

Ohio Attorney General Dave Yost has complained that legal fees in the opioid litigation case are too high. The judge has also warned attorneys to fly coach and limit their hotel rooms to $450 a night.

Many of the lawyers involved in the case are major political donors. Motley Rice attorneys gave over $700,000 to political candidates in 2018, while the law firm of Simmons Hanly Conroy donated over $1 million, much of it going to Missouri Sen. Claire McCaskill (D) in her failed bid for reelection.

Coincidentally, McCaskill released a report last year that was sharply critical of physician and patient advocacy groups for accepting money from opioid manufacturers. Three organizations cited in the McCaskill report — the American Academy of Pain Medicine, American Geriatric Society, and the American Pain Society — were named as defendants in opioid lawsuits filed by Simmons Hanly.  

‘Injectrode’ Could Revolutionize Neuromodulation Pain Treatment

By Pat Anson, PNN Editor

A team of scientists and engineers has developed a flexible electrode that can be injected into the body to stimulate damaged nerves, relieve chronic pain and treat other conditions.

The so-called “injectrode” could revolutionize neuromodulation therapy by eliminating the need for invasive spinal cord stimulators and other surgically implanted medical devices.

Researchers used a liquid silicone base -- similar to surgical glue – and mixed it with small metal particles to make it electrically conductive.

When injected around a nerve and allowed to cure, the injectrode performs much like a metal wire, but remains flexible.

Current neuromodulation treatments often rely on rigid implanted devices that can cost hundreds of thousands of dollars, require complex surgeries to install, and often fail or need to be replaced.

IMAGE COURTESY OF NEURONOFF

"Typical implants are really stiff, and so as the body moves, they wear and tear and break down. Our liquid cures, and the result is much closer to the normal elasticity of tissue. You can actually stretch it and increase its size 150 percent to 200 percent without losing its conductivity," says co-author Kip Ludwig, PhD, a professor of biomedical engineering and neurological surgery at University of Wisconsin-Madison.

“By virtue of its simplicity, the Injectrode has the potential to be less invasive, more robust, and more cost‐effective than traditional electrode designs, which could increase the adoption of neuromodulation therapies for existing and new indications.”

Ludwig and his colleagues reported their findings in the journal Advanced Healthcare Materials.

The injectrode has been tested on laboratory animals to stimulate their nervous systems. It was used in pigs to induce heart rate changes by stimulating the vagus nerve in the neck, an approach that's shown promise for treating heart failure, hypertension, lupus and cluster headaches.

"We essentially went through the standard repertoire of electrochemical tests to show this acts like a standard wire electrode that could be used to stimulate the nerve," says co-author James Trevathan, PhD, a postdoctoral fellow in Ludwig's lab.

Ludwig co-founded Neuronoff, a company based on the injectrode, with Case Western Reserve University biomedical engineering professor Andrew Shoffstall, PhD, and Neuronoff CEO Manfred Franke, PhD. Neuronoff recently secured a $2.1 million grant from the National Institutes of Health to further develop the injectrode to stimulate spinal nerves as a treatment for chronic back pain.

The researchers are testing a scheme in which they inject the fluid around the nerve, then extrude a thin insulated string of the material back to just underneath the surface of the skin, where they inject more of the composite material. Then they can use a basic transcutaneous electrical nerve stimulation (TENS) unit to stimulate the nerve from the surface of the skin.

"We're making a bypass from the surface of the skin to the location we want to stimulate," says Ludwig, who envisions using a robotic surgical system to install the injectrode in a procedure similar to getting a tattoo.

"As we learn more and more about how to interface with the nervous system, we're not limited to what we've implanted through an invasive surgical procedure. We can actually change how we stimulate, how we talk to the nerve, because we're essentially just routing our connection to this deep nerve back to the surface of the skin."

Spinal cord stimulators have some of the worst safety records among medical devices, according to a 2018 report by investigative journalists. Stimulators are often touted as safer alternatives to opioid pain medication, but 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.  

Icy Virtual Reality Freezes Out Pain

By Pat Anson, PNN Editor

Everyone knows that an ice pack or cold compress can help sooth aching joints and sore muscles. Cold temperatures slow blood circulation, reducing both pain and inflammation.

Researchers at Imperial College London took that basic first aid measure a step further by using virtual reality (VR) to immerse people in scenes of an icy Arctic landscape. And just like real ice, the VR video reduced pain perception and sensitivity.

Findings from the small study, published in the journal Pain Reports, add to growing evidence that VR technology can not only distract people from their pain, but may also activate the body’s pain-fighting response.

“One of the key features of chronic pain is you get increased sensitivity to painful stimuli. This means patients’ nerves are constantly ‘firing’ and telling their brain they are in a heightened state of pain,” first author Sam Hughes, PhD, said in a press release.

"Our work suggests that VR may be interfering with processes in the brain, brainstem and spinal cord, which are known to be key parts of our inbuilt pain-fighting systems and are instrumental in regulating the spread of increased sensitivity to pain.

In the study, 15 healthy volunteers were given a topical cream on the skin of their legs containing capsaicin – the spicy chemical in chili peppers that makes your mouth burn. The capsaicin sensitized the skin, making it more sensitive to pain from a small electric shock.

Participants were then asked to rate their pain on a scale of 0-100 (from ‘no sensation’ to ‘worst pain imaginable’) while looking at a still image of an Arctic scene on a computer monitor or watching this National Geographic video of Arctic exploration through a VR headset.

Researchers found that pain from the capsaicin cream was reduced following the VR immersion. The volunteers’ skin was also less sensitive to the electric shocks.  The same effect was not seen in people who only looked at still images of the polar environment.

Hughes and his colleagues plan further studies of VR to see what kind of dosing regimen works best for pain – such as 30 minutes of VR, four times a day – and if the pain relieving effects would be cumulative or remain only temporary.

“The aim of this study was to show VR has the ability to change the pathological processing associated with chronic pain,” says Hughes. “Using this approach does seem to reduce the overall intensity of the ongoing pain as well as the response we get on the skin. We think there could be changes in the body’s pain relief system’s which can affect how pain sensitivity is processed in the spinal cord.

“There are still many things to figure out, but one exciting aspect of our study is that the VR design we used is completely passive – meaning patients don’t need to use their arms. Potentially, it could mean that patients who are bed-bound or can't move their limbs, but with chronic pain, could still benefit from this approach.”

Previous studies have found that VR can make small improvements in the pain of hospitalized patients recovering from surgery or suffering from neurological, orthopedic, gastrointestinal or cancer pain.