COVID-19 Research Could Lead to New Painkillers

By Pat Anson, PNN Editor

A loss of taste or smell is one of the early signs of being infected with COVID-19. Scientists say the virus appears to bind itself to nerves in the nasal cavity, causing inflammation that blocks sensory signals associated with smell and taste from reaching the brain.

Researchers at the University of Arizona believe SARS-CoV-2 may have a similar effect on pain signals and essentially acting as an analgesic. That may explain why nearly half the people infected with COVID-19 experience few or no symptoms, even though they are still able to spread the disease.

"It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you're walking around all fine as if nothing is wrong because your pain has been suppressed," says Rajesh Khanna, PhD, a pharmacology professor at UArizona Health Sciences College of Medicine Tucson.

"You have the virus, but you don't feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that's of enormous value."

Viruses cause infections by attaching themselves to protein receptors on cell membranes. Early in the pandemic, scientists established that SARS-CoV-2 enters the body via the ACE2 protein on the surface of many cells. Recent preliminary studies suggest there is another route to infection, in which the virus attaches itself to a receptor called neuropilin-1.

"That caught our eye because for the last 15 years my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin," said Khanna. "So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing."

How COVID-19 Blocks Pain Signals

Many biological pathways send pain signals to the brain. One is through a protein called vascular endothelial growth factor-A (VEGF-A), which plays an essential role in blood vessel growth but also has been linked to inflammatory diseases such as rheumatoid arthritis and osteoarthritis. VEGF-A binds to neuropilin in a way that triggers a cascade of pain signals.

In research on rodents, Khanna says his team found that the SARS-CoV-2 binds to neuropilin in exactly the same location as VEGF-A, which “completely reversed the VEGF-induced pain signaling." The virus had an analgesic effect at both high and low doses.

Khanna and his colleagues’ groundbreaking research has been published in the journal PAIN. He also authored a blog post in the Daily Beast to explain the findings in layman’s terms. He says the discovery could not only lead to new treatments for COVID-19, but new ways to block pain signals.

“Sneaky virus, fooling people into believing that they do not have COVID-19. But, ironically, it may be gifting us with the knowledge of a new protein, critical for pain. Two roads emerge in the forest ahead: (1) block neuropilin-1 to limit SARS-CoV-2 entry, and (2) block neuropilin-1 to block pain,” Khanna wrote in the Daily Beast.

In future studies, Khanna say his research team will be examining neuropilin as a new target for non-opioid pain relief. They have already tested existing neuropilin inhibitors developed to suppress tumor growth in cancers and found they provided the same pain relief as SARS-CoV-2 when it binds to neuropilin.

"We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief," Khanna said. "We have a pandemic, and we have an opioid epidemic. They're colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic."

Survey: Painkillers Bigger Problem than Alcohol

By Pat Anson, Editor

A new poll is adding further fuel to the fire over opioid abuse and the disproportionate amount of attention it gets compared to other health problems.

The survey by the Kaiser Family Foundation found that two-thirds of Americans consider the abuse of opioid pain medication an extremely or very serious problem. And four out of ten said they knew someone who was addicted to prescription painkillers, often a close friend or family member.

The problem is so serious that more Americans now consider painkillers a bigger problem than alcohol (66% vs. 57%), even though four times as many Americans die from alcohol related causes than from opioids.

Nearly 19,000 Americans died from prescription opioids in 2014, according to the Centers for Disease Control and Prevention. The National Institutes of Health estimates 88,000 people die annually from alcohol related causes.

Alcohol misuse is also estimated by NIH to cost the U.S. economy nearly $250 billion annually, while the “economic burden” of opioid abuse was estimated by the DEA at $53 billion in 2011.   

The Kaiser Foundation poll comes in the middle of an election season, as the White House and Congress consider various funding measures to address the so-called epidemic of opioid abuse and addiction.

The survey found that a large majority of Americans believe federal and state governments, doctors, and individuals who use prescription opioids are not doing enough to fight opioid addiction. Only about a third said police officers weren’t doing enough to enforce drug laws, a sign that many Americans don’t consider opioid abuse just a law enforcement issue.

Asked which policy efforts would be very or somewhat effective in reducing opioid abuse, over eight in ten said doctors and medical students should have better training in pain management and that there should be increased access to addiction treatment programs.  Less than half said putting warning labels on prescription opioids explaining the risk of addiction would be effective. Respondents were not asked if access to opioid pain medication should be reduced.

Policies Rated Very or Somewhat Effective in Fighting Opioid Abuse

• 88% Increase pain management training
• 86% Increase access to addiction treatment
• 84% Public education and awareness programs
• 83% Increase research about pain and pain management
• 82% Monitor doctors’ prescribing habits
• 63% Encourage disposal of extra pain meds
• 60% Reduce stigma of opioid addiction
• 48% Put addiction warning labels on opioid bottles

Putting the issue in perspective, while most Americans consider painkiller abuse a serious problem, the issue ranks well behind several other health problems such as cancer, diabetes, obesity and heart disease.

Health Problems Considered Extremely or Very Serious

• 86% Cancer
• 78% Diabetes
• 74% Lack of access to mental healthcare
• 73% Obesity
• 72% Heart disease
• 71% Contaminated drinking water
• 70% Heroin abuse
• 66% Painkiller abuse
• 61% Lack of access to healthcare
• 57% Environmental contamination
• 57% Alcohol abuse
• 54% Lack of access to affordable food

The Kaiser Foundation survey was conducted in mid-April in a random telephone sample of 1,201 American adults. The poll is estimated to have a sampling error of 3 percent.

To see the complete results of the Kaiser poll, click here.

Experimental Painkiller Leaves Six Hospitalized

By Pat Anson, Editor

Six men have been hospitalized in France after being sickened during a clinical trial of an experimental painkiller. One victim has been declared brain-dead and four others are in critical condition.

(Update: The man who was brain-dead has died, according to local media reports.)

The Phase I trial of the drug has been suspended and all 90 participants have been urged to contact a hospital.

According to reports, the experimental drug being developed by the Portuguese company Bial inhibits a brain enzyme that degrades endogenous cannabinoidsthat are produced naturally by the brain to relieve pain.

By degrading the enzyme called FAAH, Bial hopes to develop compounds that increase brain levels of cannabinoids for use as anti-depressants or pain relievers.

French health officials say the unidentified drug “does not contain cannabis or any derivative of cannabis.”

"We were informed that five participants showed severe symptoms. Following the best international medical practices, they were immediately transferred by the company responsible for conducting the clinical trial to observation at the University Hospital of Rennes, being currently under permanent medical supervision," Bial said in a statement.

Phase I trials are usually conducted to prove the safety of a drug, while the effectiveness of a drug is tested in Phase II and III clinical studies.

The men who were hospitalized were all given multiple doses of the drug, starting January 7. Three days later they started developing neurological symptoms. Two people who were given a harmless placebo developed no symptoms.

“It is definitely the product that is responsible,” said Gilles Edan, head of neuroscience at Pontchaillou Hospital in Rennes, where the men are being treated. She said there is no anti-dote to the drug and its effects could be “irreversible.”

The trial in Rennes was being conducted by Biotrial, a firm that conducts early clinical trials in France and Newark, New Jersey. In France, volunteers can earn nearly $5,000 for participating.  

According to the Daily Mail, Biotrial is able to fast-track early patient studies by “combining the favourable regulatory environment in Western Europe with fast and efficient patient recruitment in Eastern Europe.” 

 “Our thoughts go out to the volunteers and their families. We are working hand in hand with the Health Authorities to understand the cause of this accident,” the company said in a statement.

“The trial has been conducted in full compliance with the international regulations and Biotrial’s procedures were followed at every stage throughout the trial, in particular the emergency procedures for the transfer of subjects to the hospital.”

Survey Finds Doctors Need More Addiction Education

By Pat Anson, Editor

Many primary care physicians -- the top prescribers of opioid pain medication in the United States – lack a basic understanding of how the drugs can lead to abuse and addiction, according to a new survey by the Johns Hopkins Bloomberg School of Public Health. The survey was conducted by several longtime critics of opioid prescribing practices who advocate tighter restrictions on painkillers.

The survey of over 500 practicing internists, family physicians, and general practitioners was conducted by mail in early 2014. Primary care physicians treat over half of the chronic pain patients in the U.S. and prescribe most of the pain medication.

The survey results, reported in the Clinical Journal of Pain, found that nearly half the physicians incorrectly believe that abuse-deterrent pills – which are harder to crush or liquefy for snorting or injecting – are less addictive than their standard counterparts. .

"Physicians and patients may mistakenly view these medicines as safe in one form and dangerous in another, but these products are addictive no matter how you take them," says study leader G. Caleb Alexander, MD, an associate professor in the Bloomberg School's Department of Epidemiology and co-director of the school's Center for Drug Safety and Effectiveness.

“Opioids serve an important role in the treatment of some patients. However, our findings highlight the importance of patient and provider education regarding what abuse-deterrent products can and cannot do. When it comes to the opioid epidemic, we must be cautious about overreliance on technological fixes for what is first and foremost a problem of overprescribing."

Every primary care physician who was surveyed thought that prescription drug abuse was a problem in their communities. Large majorities also supported efforts to reduce abuse, including patient contracts, urine drug testing, databases that monitor opioid prescribing, and greater restrictions on the marketing and promotion of opioids.

About a third of the doctors incorrectly reported that the most common route of prescription drug abuse is by means other than swallowing pills. Numerous studies have shown that most drug abuse is through oral ingestion, followed by snorting and injection.

Interestingly, one third of the physicians (33%) believed that efforts to reduce opioid abuse have had a chilling effect on pain management practices, and were preventing legitimate pain patients from gaining access to appropriate treatment.

Despite that finding, Alexander said further efforts are needed to combat opioid abuse, saying “doctors continue to overestimate the effectiveness of prescription pain medications and underestimate their risks.”

"For the sake of making a dent in an epidemic of injuries and deaths, we have to find ways to make changes. Too many lives are at stake to stick with the status quo," he said.

Two of the co-authors of the study are Andrew Kolodny, MD, and Stefan Kruszewski, MD. Kolodny is president of Physicians for Responsible Opioid Prescribing, a group that has lobbied Congress and petitioned the Food and Drug Administration to limit access to opioids. Kruszewski has served as an expert witness in multiple lawsuits against pharmaceutical companies.

Their research was supported by the Robert Wood Johnson Public Health Law Research Program and the Lipitz Public Health Policy Award at Johns Hopkins Bloomberg School of Public Health.

The Centers for Disease Control says over 16,000 Americans die annually from painkiller overdoses, an estimate that dates back to 2010. Most of those deaths also involved alcohol or other drugs.

Several recent studies suggest the tide of opioid abuse has turned in the U.S.

Dispensing of opioid pain medication and painkiller overdoses have declined substantially since 2010, according to a recent study published in JAMA Internal Medicine.

The number of prescriptions filled in the U.S. for hydrocodone has also declined, the first concrete evidence that restrictions on hydrocodone prescribing that were adopted in 2014 are starting to have an impact. Hydrocodone is no longer the most widely filled prescription in the U.S.

The National Institutes of Health estimates that only about 5 percent of pain patients become addicted to opioids after using them as directed for a year.

There is No 'Epidemic' of Painkiller Overdoses

By Ken McKim

There is no "epidemic" of opioid overdoses. If 16,000 deaths in a year is an epidemic, then we really need to focus on the pandemic that is the over 100 million people in the U.S. who suffer from chronic pain.

For example, car crash fatalities in 2013 claimed more lives than opioid overdoses (there were 30,057 fatal motor vehicle crashes in the United States in 2013 in which 32,719 deaths occurred according to IIHS). As this qualifies as an epidemic by some people's twisted logic, I suggest we handle reducing car crash fatalities in the same manner that we regulate the prescribing of painkillers.

Effective immediately, you will have to own your car for two months before you can get a license to drive it. To obtain a driver's license, you must first establish a history with the DMV by visiting them at least two times per month for two months, paying $40 per visit during the two-month period you are waiting to get approved for your license.

Once you have your driver's license, you will only be able to purchase gasoline at particular gas station with a signed fuel-certificate from the DMV, which will allow you to purchase what the DMV thinks is an adequate supply of gas for a 30-day period.

For each new 30-day supply of gasoline you must obtain a new fuel certificate from the DMV, which will require another $40/five-hour appointment at the DMV.

If you try to take your DMV fuel-certificate to a different gas station than you normally use, your fuel-certificate may be refused and your name entered into a national database as someone guilty of "fuel seeking behavior."

Additionally, you will not be able to refill your gas supply after 3PM on Fridays, weekends or holidays. Your gas allotment must last for the full 30-day time-frame specified by the DMV. If you run out of gas before that 30-day period is up, you will not be able to get another fuel-certificate until the 30-day calendar period has ended. So remember, you should not be driving anywhere except to and from work, with possibly a once a week trip to the grocery store.

NOTE: Asking for more than your allotted fuel allowance will also constitute "fuel seeking behavior" and the DMV may choose to no longer see you.

The DMV also reserves the right to randomly smog check your vehicle at any time. If your vehicle fails the smog inspection, your driver's license will immediately be revoked.

NOTE: You must pay the cost of the smog inspection yourself.

I'm sure this will result in an immediate drop in automobile deaths. You're welcome.

This column is republished with permission from Ken McKim’s website, “Don’t Punish Pain.”

Ken began advocating for pain patients when his wife was diagnosed with Crohn’s disease – and he came to realize that the chronically ill were often stigmatized by society. That realization led him to make a 32-minute video called "The Slow Death of Compassion for the Chronically Ill"

Ken has a series of other informative videos on You Tube.

Half of Americans Say Painkiller Abuse 'Serious Problem'

By Pat Anson, Editor

Over half of all Americans believe the abuse of a prescription painkillers is an extremely or very serious problem, according to a new poll by the Boston Globe and Harvard School of Public Health that documents the widespread concern – and misconceptions – the public has about opioid pain medication.

While nearly half (45%) believe painkillers are prescribed too often or in doses that are bigger than necessary, a majority (51%) believe that current regulations on the prescribing and availability of opioid pain medication are about right.  

Less than a third (29%) believe that regulations make prescription painkillers too easy for people to get.

The telephone poll of over 1,000 adults, which was conducted in mid-April, found that most Americans were more concerned about prescription painkiller abuse than they were about heroin.

Nearly one in four (39%) said they knew someone who had abused pain medication.

"For much of the public, the issue of prescription painkiller abuse is not just a remote concern; it's a problem they see in their personal lives," said Robert J. Blendon, a professor of Health Policy and Political Analysis at Harvard T.H. Chan School of Public Health.

People who know someone who has abused prescription painkillers hold different views about the problem than those who do not. They are significantly more likely to think painkiller abuse is an extremely or very serious problem (64% vs. 43%) and that the problem has gotten worse over the past five years (56% vs. 28%).

Of those who have known someone who has had an abuse problem, a majority say it has had a major harmful effect on the user's family life (67%), work life (58%), and health (55%). In addition, 21% say that the person's abuse of prescription painkillers led to their death.

Although studies have found that only a small percentage of pain patients become addicted to opioids, many Americans believe it is easy to get hooked on them. Nearly half of those surveyed (44%) say it is “very likely” that a person taking prescription painkillers will become addicted.

About one in five (21%) of the survey respondents said they had taken a prescription painkiller in the past two years. Of those, one in four (26%) reported they had been very or somewhat concerned that they could become addicted. Nearly two-thirds (61%) said they had talked to their doctor about the risk of addiction.

You can view the complete poll findings here.

While many respondents (39%) believe prescription painkiller abuse has gotten worse over the last five years, there are signs it has been abating.

Hydrocodone prescriptions fell by 8% last year and it is no longer the most widely prescribed medication in the U.S.

A recent report by a large national health insurer found that total opioid dispensing declined by 19% from 2010 to 2012 and the overdose rate dropped by 20 percent.

Survey: Most Pain Patients Don't Abuse Painkillers

By Pat Anson, Editor

Only a small percentage of chronic pain patients misuse or abuse their opioid painkillers, according to a wide ranging survey by the Partnership for Drug-Free Kids that also found a “disconnect” between patients and their doctors about opioid prescribing.

About one in ten pain patients (7% of chronic pain patients and 13% of acute pain patients) admitted misusing their opioid medications. Nearly half took longer to finish their prescriptions than directed – which was usually an effort to save the pain medication for another time.

More than one in ten (13% of chronic pain patients and 15% of acute pain patients) admitted using someone else's opiate prescription.

The online survey of 705 pain patients and 360 prescribing physicians was conducted by the research firm Whitman Insight Strategies (WINS) earlier this year.

About two-thirds of the opioid prescribers said they “always” warned their patients about the risk of addiction and dependency.

But when patients were asked who, if anyone, explained to them the potential for becoming dependent or addicted to painkillers, 19% of chronic pain patients and 40% of acute pain patients said "no one."

The survey also found that most patients pay little attention to the proper storage and disposal of pain medication. Only 11% of chronic pain patients and 13% of acute pain patients said they were concerned that someone else in their household might use their medications.

Less than half of chronic pain patients (42%) who have children said they store their medication somewhere their kids can’t reach. Most patients said their doctors never discussed the proper storage and disposal of painkillers.

"This research highlights key opportunities for prescribers of Rx opiates and their patients to have better communication around proper use and disposal of prescribed painkillers," said Marcia Lee Taylor, Interim President and CEO of the Partnership for Drug-Free Kids.

"The Centers for Disease Control has deemed abuse of prescription painkillers an 'epidemic,' and we can all do our part to help turn the tide on this critical health issue. Prescribers and patients can become more aware of the repercussions surrounding the improper storage and disposal of Rx pain medications and talk more at length in order to improve doctor-patient communication and help curb abuse."

The survey also found that many physicians are concerned about patients misusing their pain medication – by either taking too little or taking too much.

The majority of prescribers (77% of primary care physicians and 75% of pain management specialists) believe their patients do not always use their prescribed opiates in accordance with instructions. Twenty percent of the primary care physicians said they don’t feel comfortable prescribing opiates at all.

"This research suggests to us that prescribers need to feel more confident in assessing the potential risk of misuse or abuse of the Rx medicines, but unfortunately many of them feel they have not received proper training to assess those risks. There is a lot more we can do to help prescribers feel they have the proper tools they need to feel comfortable prescribing these medicines and taking action if a patient is abusing them," Taylor said.

The survey also found that most pain patients would prefer alternatives to opioids. About 9 in 10 chronic pain patients have tried an alternative treatment such as physical therapy and massage. Many were hindered in their use of alternative therapies by restrictions on insurance coverage.