Does Childhood Trauma Increase Risk for Opioid Misuse?

By Pat Anson, PNN Editor

Did a parent humiliate or swear at you as a child? Were you ever molested? Did you live with a problem drinker or someone who went to prison? Were your parents ever separated or divorced?

Those are some of the questions posed to over 1,400 college students in a study by researchers at the University of Georgia, who wanted to assess the relationship between childhood trauma and the misuse of prescription opioids later in life.

Their research, recently published in the Journal of American College Health, found that most students had at least one adverse childhood experience (ACE). But those who reported four or more ACEs were almost three times more likely to misuse opioid medication.

Based on that finding, the researchers say healthcare providers should consider a patient’s experience with childhood trauma before prescribing them opioids.

“Our findings suggest need to include assessment of ACEs as a screening criterion for opioid prescription and administration among college-aged individuals,” wrote lead author Janani Thapa, PhD, an associate professor in UGA’s College of Public Health.

Many doctors already use screening tools to assess whether a patient is at risk for opioid misuse. They look up their prescription drug history, or ask patients if they’ve been sexually abused or have family members with a substance use disorder.

But Thapa and her colleagues think that assessment should go further, incorporating a wider range of childhood trauma, such as whether a patient didn’t have enough to eat or had to wear dirty clothes as a child.  

“Prevention of opioid misuse demands careful consideration of the traumatic exposure of the patient,” they said. “Current opioid assessment measures, including patient or family interviews, and prescription monitoring, may need to incorporate patients’ traumatic history for proper chronic pain management and integrated care.”

Penalizing Patients

The use of opioid screening tools is controversial. Some patients resent being asked about their childhood trauma – which they see as irrelevant to their health problems and pain management as adults.   

“I overcame my early life abuse until an ignorant doctor used that childhood abuse without psychiatric consultation to put labels on me and refuse medicine for pain,” one patient told us.

“Just because a patient may have been sexually abused or has family members who are addicts/alcoholics, does not mean the patient will be,” said another. “To penalize a person who is in excruciating pain due to no choice of their own, is cruel and inhumane.”

But a pain management expert says opioid screening tools have their place, because childhood trauma can have a lasting impact. 

“Most studies have shown that 4 in 5 people with an Opioid Use Disorder have at least one ACE,” says Lynn Webster, MD, past president of the American Academy of Pain Management and a PNN contributor. “I consider ACEs a form of post-traumatic stress disorder. It affects emotion regulation, causing an inability to modulate distressing emotions in a healthy and adaptive way. ACEs create a maladaptive response to stress. The earlier in life the ACEs occur, the more effect they will have later in life.” 

Over 20 years ago, Webster developed one of the first opioid screening tools for doctors, a short survey that asked patients if they had a history of substance abuse, sexual abuse, or any mental health issues. In his own practice, Webster found the survey helpful in identifying patients at risk of abusing opioids, but he later came to regret how the screening tool was “weaponized” against patients, particularly women, and used by other doctors as an excuse to deny patients opioids. 

“The Opioid Risk Tool (ORT) incorporates pre-adolescent trauma to help identify females who were at greater risk of OUD from what I believe is a form of PTSD. If I were to develop the tool today, I would probably make it gender neutral, but the increased risks for females would remain,” Webster said in an email. 

Webster agrees with the University of Georgia researchers that ACEs should be used to help assess whether a patient is at risk of abusing medication. But he says a high number of ACEs should not be used to avoid prescribing opioids to someone who has a medical need for them.  

Illicit Drug Use by Teens Fell Significantly in 2021

By Pat Anson, PNN Editor

Substance abuse by U.S. teenagers declined significantly this year, according to the results of a new national survey that found the use of prescription opioids by adolescents fell to the lowest level in nearly two decades.

Illicit drug use by 10th graders fell by nearly 12 percent in 2021, and by about 5% for eighth and 12th graders. The findings represent the largest one-year decline in illicit drug use by teens since the Monitoring the Future survey began in 1975.

The study by University of Michigan researchers found that teenagers reported increased feelings of boredom, anxiety, depression and loneliness in 2021 – no doubt fueled by pandemic-related fears and isolation. But unlike their adult counterparts, young people overall did not increase their use of marijuana, alcohol and other drugs.

“We have never seen such dramatic decreases in drug use among teens in just a one-year period. These data are unprecedented and highlight one unexpected potential consequence of the COVID-19 pandemic, which caused seismic shifts in the day-to-day lives of adolescents,” Nora Volkow, MD, Director of the National Institute on Drug Abuse, said in a statement.

“Moving forward, it will be crucial to identify the pivotal elements of this past year that contributed to decreased drug use – whether related to drug availability, family involvement, differences in peer pressure, or other factors – and harness them to inform future prevention efforts.”

The Monitoring the Future survey is given annually to students in eighth, 10th and 12th grades, who self-report their drug use behaviors and attitudes. The results from this year’s survey were collected from February through June 2021. Over 32,000 students enrolled in 319 public and private schools in the U.S. participated, with some taking the survey at home and others while at school.

The percentage of students who reported using any illicit drug other than marijuana within the past year decreased significantly. Among 12th graders, for example, 7.2% reported using an illicit drug in 2021, compared to 11.4% in 2020.

Decreases were also reported in the use of alcohol by 12th graders (46.5% in 2021 vs. 55.3% in 2020) and in marijuana (30.5% in 2021 vs. 35.2% in 2020).

Significant declines in use were also reported by students in 2021 for a wide range of drugs, including cocaine, heroin, hallucinogens, cigarettes and nonmedical use of amphetamines, tranquilizers, and prescription opioids.

The decline in drug use by teens is not a one-year fluke and is part of a long running trend. For example, the use of Vicodin by 12th graders has fallen by nearly 92 percent since its peak in 2003. The use of OxyContin has declined by 83% since its peak in 2005.   

MONITORING THE FUTURE SURVEY

“In addition to looking at these significant one-year declines in substance use among young people, the real benefit of the Monitoring the Future survey is our unique ability to track changes over time, and over the course of history,” said Richard Miech, PhD, who led the Monitoring the Future study at the University of Michigan. “We knew that this year’s data would illuminate how the COVID-19 pandemic may have impacted substance use among young people.”

Not all the news is good. The researchers found that adolescents who suffered severe stress, anxiety or depression due to the pandemic, experienced financial hardship, or whose parents used drugs were most likely to use drugs themselves.

Other studies have found that adults who regularly use recreational drugs increased their drug usage during the pandemic. A new study of alcohol sales in 16 U.S. states found a major increase in wine and liquor sales in the first few months of the pandemic, by as much as 20 to 40 percent in some states.

Another recent study found that opioid prescribing briefly increased in the early stages of the pandemic, as patients postponed corrective procedures and it became harder to obtain non-opioid therapies for pain such as massage and physical therapy. Opioid prescribing returned to previous levels after a few months.   

The CDC announced last month that the U.S. has seen over 100,000 drug deaths in the 12-month period ending in May, 2021. The record-high spike in overdoses is thought to be primarily a result of pandemic lockdowns and the continuing spread of illicit fentanyl.   

Cannabis Users May Risk Harmful Drug Interactions

By Pat Anson, PNN Editor

A recent survey found that nearly half of American adults (49%) have tried marijuana, a figure that has risen steadily in recent years as more states legalize medical and recreational cannabis. While the Gallup poll didn’t ask people why they used marijuana, it’s fair to say many are experimenting with cannabis products – and cannabidiol (CBD) in particular – as alternatives to mainstream medical treatment.

And that could be a problem for people with chronic pain and other illnesses, according to researchers at Washington State University, who found that CBD interferes with two families of enzymes that help metabolize pain relievers and other drugs prescribed for a variety of medical conditions. As a result, the medications’ positive effects might decrease or the drugs could build up in the body and become toxic.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Philip Lazarus, PhD, a professor of pharmaceutical sciences and senior author of two new studies appearing in in the journal Drug Metabolism and Disposition.

“It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

One study focused on enzymes known as cytochrome P450s (CYPs), while the second study looked at enyzymes called UDP-glucuronosyltransferases (UGTs). Together, the two enzyme families help metabolize and eliminate more than 70 percent of the most commonly used drugs from the body.

The WSU researchers studied three cannabinoids — tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) -- and how they interact with CYP and UGT enzymes. Of particular interest to the researchers are the metabolites produced by cannabinoids as they break down in the body.     

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “The metabolites that result from that process stay in your body for much longer -- up to 14 days -- and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.”

The researchers found that cannabinoids and the major THC metabolites strongly inhibit several key CYP enzymes in the liver that play a role in metabolizing anti-cancer drugs, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, anti-epileptics and other medications. Cannabinoids also inhibited two of the primary UGT enzymes in the liver.

Atlhough the liver is considered the most important organ for the metabolism of drugs, kidneys also play a vital role, clearing toxins and other drugs from the body. Researchers found that CBD blocked three enzymes that account for about 95 percent of kidney UGT metabolism.

“If you have a kidney disease or you are taking one or more drugs that are metabolized primarily through the kidney and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” Lazarus said.

The interactions between CBD and UGT enzymes could be especially risky for patients with acute kidney disease, kidney cancer or HIV, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” Nasrin said. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”

More research is needed to fully understand the drug-drug interactions that cannabis may have. Drugs.com has a list of 387 drugs that are known to interact with cannabis, with 26 categorized as major interactions and 361 described as moderate.

Medications known to have major interactions with cannabis include several opioids, such as codeine, fentanyl, buprenorphine, hydrocodone, methadone, morphine and oxycodone.

Spending Time in Nature Can Reduce Chronic Pain

By Gabriella Kelly-Davies, PNN Columnist

A few months ago, I took part in a panel discussion with three other women who live with migraine or chronic headaches. One speaker, Australian journalist Sarah Allely, described how immersing herself in nature helped to relieve her debilitating headaches, anxiety and depression after a mild traumatic brain injury. It also drastically improved her focus and concentration.

Sarah’s brain injury occurred in 2015, when a passing car knocked her off her bicycle. Afterwards, a headache erupted in the base of her skull whenever she tried to read, write, watch television, or listen to music. She also struggled to concentrate and couldn’t work as a journalist for eight months.

Noisy environments such as bars, cafes and social gatherings that for years had energized Sarah, became unbearable. Despairing, she asked her medical team for advice. Her doctors admitted there wasn’t much they could do and suggested she learn to accept the situation. Sarah’s spirit sank as she contemplated a bleak future without all the things that had previously given her purpose and pleasure.

But that all changed when her friends invited her on a bush walk.

While trekking through the bush, Sarah’s headache lifted. So did her anxiety and depression. She wondered whether it was a fluke or if spending time in nature had reduced her symptoms.

During the following weeks, Sarah visited local bushland whenever possible. To her surprise, every time she did this, her headache, anxiety and depression eased. Intrigued, she wondered whether going to a local park or sitting in her garden would have a similar effect. She tried it. To her amazement, it worked!

A while later she stumbled across some magazine articles about research around the healing powers of nature. Curious about why her symptoms eased whenever she spent time in nature, Sarah decided to make an audio documentary. She wanted to understand the science behind her experience and the “optimum dose of nature” to relieve her physical and emotional pain.

During her research, Sarah came across several American scientists who were studying the science underpinning the healing effects of nature. Excited, she interviewed them, turning the conversations into six episodes of a podcast series she named Brain on Nature.

In the free podcast, Sarah shares her experiences discovering the healing powers of the natural world. Each episode follows her quest to discover why the natural environment changed her brain, helping her recover from a brain injury.

Seeking Connections With Nature

The scientists Sarah interviewed told her they were asking the same questions as her. Their studies found spending time in nature improved psychological and physical health, but they couldn’t pinpoint the precise reason for this response. Still, they were confident certain theories did help explain what was happening.

One of these theories is called biophilia, a belief that humans have an innate tendency to seek connections with nature. But for many of us living in bustling urban settings, constant traffic noise, bright lights, sirens, flashing billboards and yelling are the norm, and connecting with nature is a dream rather than a reality.

Instead of relaxing or exercising in a natural environment, we multitask, work on computers, talk on mobile phones, scroll through social media and send text messages. Living this way increases our stress levels, and for people with chronic pain, this can mean more pain.

But there is good news. Several studies show that when people turn off their electronic devices and sit in a quiet garden or stroll in a park, they feel refreshed and relaxed.

Pain specialists know that when a person living with chronic pain is calm, the volume of pain signals racing through their nervous systems is less than when they are anxious, angry or upset. So it makes sense that pain could reduce after spending time in a relaxing environment such as a garden or park.

Another possible explanation for Sarah’s experiences comes from Rachel and Stephen Kaplan’s Attention Restoration Theory. The Kaplans propose that exposure to nature is not only enjoyable but also relaxing and revitalizing. In Sarah’s case, whenever she spends time in the mountains on a weekend, she remains headache-free the following week. Her focus and concentration are also better. 

Fortunately, benefiting from the healing effects of nature is not about climbing Mount Everest or going on three-day treks in the forest. It can be a 10-minute walk in a local park or sitting in the garden smelling the flowers.

Once she understood the natural world was helping her injured brain to recover, Sarah felt compelled to share her learnings with others whose health might benefit from a dose of nature.  

“No one in the medical world suggested immersing myself in nature could reduce my symptoms,” she says. “But it works. I want others to know about it so they can try it for themselves.”

Hundreds of thousands of people around the world have listened to Brain on Nature and Sarah says their response is overwhelmingly positive.

“Two years after launching Brain on Nature, I’m still getting emails every week from people who say their life changed after listening to the podcast,” Sarah says. “I’m delighted it continues to have a positive impact and my search for answers has helped so many people.”

Sarah accepts some people might be skeptical about her belief in the natural world’s healing effects, especially if they have lived with chronic pain for several years and nothing has helped. She understands this response, but encourages anyone in pain to try a dose of nature for themselves to see if it eases their pain or improves their mood.

“When your pain is bad or you’re feeling grumpy, anxious or depressed, take yourself for a walk in the garden or a park,” Sarah suggests. “Put your phone on flight mode and see how you feel when you come back. Do you feel different? I challenge you to say spending time in nature doesn’t make any difference. So far I haven’t met anyone who can say that.”

While immersing ourselves in nature might not be a cure for chronic pain, it’s a powerful option in our pain management toolbox. Since learning about this approach, I now turn off my phone whenever we go for our morning stroll. Instead of feeling harassed by too many phone calls and text messages during our walk, I now feel relaxed and centered. And when I’m calm, I have less pain. I hope you do too.

Gabriella Kelly-Davies lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Gabapentin Is Not a Good Substitute for Rx Opioids

By Crystal Lindell, PNN Columnist 

Gabapentin (Neurontin) is not a good medication for pain relief. If it was, everyone in pain would just take it. 

A lot of doctors seem to think it is a direct substitute for opioids though. And it’s leading to a lot of suffering. 

A doctor first gave me gabapentin back in 2012. That’s when I started having debilitating pain around my right ribs. I didn’t know it yet, but it was the kind of pain that would never go away.

At the time, I was extremely uninformed on how I’d be treated as a patient with no known cause for my pain. I assumed that because I could point to exactly where the pain was coming from that the doctors would be able to figure out the cause and then fix it. That’s what always happened on House, ER, Scrubs, Grey’s Anatomy, and General Hospital.

When that didn’t happen, I still assumed my doctor would believe me. That, while I sat there crying in his office, confessing my plan to kill myself to escape the pain, at the very least he would give me the most effective medication he knew of for treating the pain. 

I was wrong on all accounts.  

While my doctor pretended he was giving me the most effective medication he knew of, he instead handed me a prescription for gabapentin. 

And I took it. Exactly as prescribed. 

He never went over side effects with me, and the list on the pharmacy pamphlet was so long that I assumed most of them were rare. So when I started gaining weight, I blamed it on being home and in pain all the time.  

When gabapentin didn’t help with the pain, I went back to my doctor and told him as much. He increased the dose, while assuring me that that was all that was needed. 

Wash, rinse, repeat, until I was on the highest allowable dose. Still with no relief. 

And to be clear, the pain was awful. It was worse than whatever you just thought of. And it was constant. That’s the killer. It never let up. I never got a break. I’d go days without even minutes of sleep because the pain kept me awake. 

The pain was so bad that suicide became a logical treatment option. What’s the point in living a life with no quality in it?

I started showing up at my doctor’s office when they opened, in tears after being awake all night in excruciating pain, asking for help. Still giving my doctor 100 percent of my trust. Still assuming he had my best interest in mind.  

I remember sitting on the exam table, wanting to die, while my friend who had driven me to his office at 7 a.m. held my hand. I begged my doctor for help. And he said, “Well what do you want me to do? I can’t up your gabapentin prescription any more. You’re on the max dose.” And then he sent me home. 

I didn’t even know enough about pain management at that point to want opioids, much less to know they were being denied to me. I didn’t know the doctors were prescribing a seizure medication because of opioid phobia. 

Not long after that, my doctor would break up with me. Or, well, whatever you call it when a doctor says he will no longer treat you and then follows it up with, “So don’t come in anymore.”

He literally gave up. And I would have too, if my pain had gone on much longer. 

‘Opioids Saved My Life’

Eventually, I found a new doctor at a university hospital. He believed me. He prescribed me enough opioids to function. And that’s literally the reason I’m still here. 

Opioids saved my life. In many ways, gabapentin almost took it. 

But it also did something else. It destroyed my trust in doctors and medical professionals. If they could look me in the eye while handing me a prescription they knew wouldn’t help me, what else could they lie about? What else were they hiding from me?

Back then, prescribing gabapentin in place of opioids was a relatively new practice. After that experience, I had hoped it would go away. Instead, it gained traction. 

According to data from IQVIA, gabapentin was prescribed over 33 million times in the U.S. in 2011, which is about the time opioid prescriptions peaked. By 2018, the number of prescriptions for gabapentin had increased to over 67 million. 

Anecdotally, a lot of people I know with various pain ailments have been offered gabapentin in place of opioids by their doctors as recently as this year.

Since I’m so open when discussing my health issues, it’s common for people I know to ask what my experience was like on various medications. I never know what to tell them when they ask about gabapentin. I’m too worried about being wrong to warn them off of it completely. After all, what if it helps them? I don’t want to keep them from anything that might relieve their pain.

Doctors don’t seem to grapple with this though. For them, addressing patient pain has moved over into optional, right alongside unnecessary cosmetic surgery.

They are literally doing harm. And the practice of giving unproven medication out for pain continues.

Here’s a 2019 article by The New York Times detailing this problem, and the lack of evidence supporting the use of gabapentin for pain.

“One of the most widely prescribed prescription drugs, gabapentin, is being taken by millions of patients despite little or no evidence that it can relieve their pain,” wrote columnist Jane Brody.

In other words, it’s been two years since The New York Times made this clear, but doctors are still prescribing it for pain.

That article misses one key point though. Brody says there are non-gabapentin alternatives to opioids that help pain, but then goes on to list “physical therapy, cognitive behavioral therapy, hypnosis and mindfulness training.”

As a pain patient, I’m here to tell you that none of those are real alternatives to opioids either. While they can all be helpful tools, they can’t replace opioids for real pain relief.

Which brings us to the problem. Our society, with guidance from the CDC, decided to take away everyone’s opioids – without having a real plan to replace them. Because there are no alternatives as good as opioid pain medication.

The general public might worry about their pain treatment if the CDC admitted that. So instead, we are sold a lie about gabapentin. We are told it is just as effective as hydrocodone for all sorts of pain, and that anyone who insists on opioids is just looking to get high.

No matter how much people use gabapentin, physical therapy and mindfulness to treat pain, they just don’t work the way opioids do.

Opioid-phobia is a big messy topic, and doctors replacing opioids with gabapentin are just one small part of that story. But for people who are suffering because of their doctor’s overreliance on gabapentin, it often feels like the most important part. 

There’s such an easy answer to this problem too: Just give people opioid medication. When used responsibly, it’s incredibly safe, cheap, and best of all, it actually works.

Crystal Lindell is a journalist who lives in Illinois.  After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome.

How to End the ‘Opioid Paradox’

By Pat Anson, PNN Editor

Three public health and pain management experts are calling for a major shift in strategy to combat the U.S. opioid crisis, one that doesn’t just focus on pill counts and punishing doctors deemed to be “overprescribing” opioids.

In an op/ed recently published online in Anesthesiology, the official journal of the American Society of Anesthesiologists, Editor-in-Chief Evan Kharasch, MD, Editor J. David Clark, MD,  and former U.S. Surgeon General Jerome Adams, MD, said current policies are failing to address what they call the “opioid paradox” --- how opioid overdose deaths have risen to record levels even as opioid prescribing has fallen to 20-year lows.

SOURCE: ANESTHESIOLOGY

“Overall, the nation’s response to the oral opioid crisis has been to tighten patient supplies and impose institutional and practitioner quality indicators based on pill counts. Governments, payers, and pharmacies have assumed authority for limiting opioid prescribing, often in indiscriminate ways, based on misinterpretation of Centers for Disease Control guidelines or based on no real guidance at all,” they wrote.

“Pill counts have become de facto standards employed by healthcare organizations to highlight their success in reducing opioid use, yet there is no discussion of how those reductions are affecting patient outcomes. One crucial problem is that agencies mandating policy restrictions do not measure, nor are they accountable for, patient outcomes. Mandated opioid prescribing limits may be too low to adequately control pain, or too high to reduce oversupply.”

The three authors say more novel and comprehensive approaches are needed to better manage the supply of prescription opioids, prevent diversion and address the opioid paradox.

“It involves immediate action to address opioid use, storage, return, and harm reduction, with a specific focus on patients and communities,” they explained.

Reduce Demand

In recent years, federal and state agencies, healthcare organizations and insurers have created new guidelines for treating pain – many of which take a one-size-fits-all approach to opioid prescribing that doesn’t take into account an individual patient’s needs.   

“Legislative, regulatory, and insurer limitations on opioid prescribing alone have not met their intended goals and are considered unlikely to achieve them. One reason is that they impose tight restrictions on an extremely heterogeneous patient population,” the authors said.

Rather than limiting or withholding opioids after surgery – which has become increasingly common --  Drs. Kharasch, Clark and Adams urge anesthesiologists and surgeons to provide patients with enough opioids for adequate pain relief, because undertreated acute pain can turn into chronic pain and become a risk factor for opioid misuse.

Smaller opioid doses may be effective in treating postoperative pain, the authors said, if they are combined with multimodal strategies that also employ non-opioid medications and therapies. So too may the use of longer-acting opioids such as methadone, which can result in less postoperative pain and relief that lasts for weeks or months after a single dose.

Proper Disposal of Leftover Pills

Hundreds of millions of opioid pills are dispensed to patients but go unused each year, according to the authors. Most leftover pills are kept by patients and few are safely stored. Only a fraction are disposed of properly or returned.

"The current difficulty of returning prescription opioids contrasts markedly with the ease of obtaining them. This is illogical and unsafe," Drs. Kharasch, Clark and Adams said.

They believe pharmacies that dispense opioids should be required to provide patients with instructions for proper return and disposal; the addresses and telephone numbers of disposal stations; and a pre-addressed, prepaid envelope for returning unused pills. Disposal stations should be available year-round, not just on “Prescription Drug Take Back” days.

Another novel approach would be opioid “buy-back” programs, similar to the gun buy-backs used by law enforcement agencies to get unneeded firearms off the street. One pilot compensation program for opioids found that 30% of surgery patients were willing to participate in buy-backs, selling their leftover opioids for up to $50.

Partial Fills

Kharasch, Clark and Adams also suggest more partial filling of opioid prescriptions. A 2016 federal law allows both patients and clinicians to request partial filling of prescriptions for hydrocodone, oxycodone and other strong Schedule II opioids. Partial filling for schedule III–V weaker opioids has been permitted for decades, but is not widely practiced.

According to one estimate, 36 million postoperative opioid prescriptions could be partially filled each year. One hurdle for partial fills is the extra paperwork and cost to pharmacies, estimated at $15 for each prescription.

“Partial opioid fills could be the single most effective intervention to deplete America’s medicine cabinets of unused prescription opioid pills, shrink the opioid pool, improve the prescription opioid ecosystem, and prevent misuse, diversion, and death,” the authors said. 

Kharasch, Clark and Adams place an emphasis on reducing diversion, even though less than one percent of legally prescribed opioids are diverted, according to the DEA. Partial fills may reduce leftover pills in medicine cabinets, but they won’t do anything to prevent the wholesale theft of opioids from hospitals, pharmacies and the pharmaceutical supply chain.

The authors also buy into the myth that most street drug users start with prescription opioids, and that pain patients denied opioids “switch to illicit drugs” and fentanyl-laced counterfeit pills.

But Kharasch, Clark and Adams do have some interesting ideas about addressing the opioid paradox – chief among them the long overdue recognition that current opioid reduction strategies have been a complete failure.

“Attempts to solve the problem by restricting patient supply alone have not succeeded, and the prescription opioid pool remains large. Additional novel efforts to shrink the pool are needed, both by diminishing demand (reducing pain through better treatment) and by facilitating opioid disposal and return,” they concluded.

WHO Panel Finds Insufficient Evidence to Review Kratom

By Pat Anson, PNN Editor

An advisory committee of the World Health Organization (WHO) has concluded there is insufficient evidence to recommend a “critical review” of kratom, which potentially could have lead to international controls on the herbal supplement used by millions to treat pain and other medical conditions.

WHO’s Expert Committee on Drug Dependence (ECDD) recommended that kratom and its two active ingredients, mitragynine and 7-hydroxymitragynine, be kept under WHO surveillance. Under international treaties, WHO is required to give an annual assessment of psychoactive substances and advise the United Nations on whether they pose a public health risk.

The ECDD’s report said regular use of kratom can lead to dependence and mild withdrawal symptoms, but that serious adverse effects were rare. Kratom comes from the leaves of the mitragyna speciosa tree in southeast Asia, where it has been used for centuries as a natural stimulant and pain reliever.

“Kratom is used for self-medication for a variety of disorders but there is limited evidence of abuse liability in humans,” the ECDD said. “Kratom can produce serious toxicity in people who use high-doses, but the number of cases is probably low as a proportion of the total number of people who use kratom. Although mitragynine has been analytically confirmed in a number of deaths, almost all involve use of other substances, so the degree to which kratom use has been a contributory factor to fatalities is unclear.”

‘Great Victory for Kratom Consumers’

In recent years, millions of Americans have discovered kratom and use it to self-treat their pain, anxiety, depression and addiction. Kratom is legal in most states, although some states and communities have banned it. The Food and Drug Administration has tried -- unsuccessfully so far – to schedule kratom as a controlled substance, which would effectively ban its sale and use in the United States.

The ECDD report was cheered by kratom advocates, including some who believe the FDA asked WHO to review kratom.

“It is a great victory for kratom consumers, for science and for the truth,” said Mac Haddow, a lobbyist for the American Kratom Association, a group of kratom vendors and consumers. "There can be no doubt that kratom should not be scheduled and that it should be responsibly regulated to protect against dangerously adulterated kratom products."

In a notice published in the Federal Register in July, the FDA called kratom “an increasingly popular drug of abuse” and said it was being “misused to self-treat chronic pain and opioid withdrawal symptoms.” Over 8,500 people responded to the FDA notice, most of them critical of the agency’s stance on kratom.

“When the FDA proposes that a natural substance like kratom be banned it is not because it’s dangerous to the public, it’s because it poses a threat to the pharmaceutical industries profits. These people have a financial interest in stopping a safe and natural substance from competing with high priced drugs,” wrote one anonymous poster.

“I suffer from chronic pain from an illness that no medication was able to help except for opioids. I became addicted, I lost my home and my job, and I was homeless for years dealing with an opioid addiction,” wrote Stewart Abe. “Kratom not only helps me get over that addiction, but it also helps me deal with the pain so I can be a functioning member of society. Without this plant in my life, the pain would be so horrific that it would not be worth living.”

“Kratom has helped countless people get away from addictive opioids and alcohol. It has all but saved my life from alcoholism and I haven’t drank in 8 years now,” wrote Davis Matthew. “Kratom has completely turned my life around and without it who knows how my life would have turned out.”

The legal status of kratom in Southeast Asia is mixed. In August, Thailand decriminalized kratom, dropped thousands of pending criminal cases involving the drug, and freed 121 inmates convicted of kratom crimes.

Hong Kong authorities recently banned kratom and seized a shipment of 2.5 tons of kratom powder that were enroute to Florida from Indonesia. Kratom use is banned domestically in Indonesia, but kratom farming is still permitted. Most kratom exports come from Indonesia, where it is considered an important cash crop.

It’s Time to Talk About Fentanyls, Plural

By Roger Chriss, PNN Columnist

The U.S. overdose crisis saw over 100,000 deaths in the year ending May 2021, driven primarily by illicitly produced fentanyl. But fentanyl is both a specific drug and a class of drugs, a distinction that is not always appreciated or understood.

At a December 2 meeting of the House Energy and Commerce’s Subcommittee on Health, Rep. Anna Eshoo (D-CA) was puzzled by testimony calling for more research into fentanyl and its chemical cousins, known as analogues.

“I don’t quite understand the need to study fentanyl, we already know what it does. It is not clear to me. Everyone has stated how devastating fentanyl is,” said Eschoo. “What is it that we don’t know about this?”

In fact, a great deal is unknown about the fentanyls causing overdoses, including their potency and potential drug interactions. As the National Institute on Drug Abuse explains, there are 15 to 30 different fentanyl analogues, including acetylfentanil, carfentanil and furanofentanyl, each with its own potency.

Fentanyl itself was first synthesized in 1959 by Paul Janssen. It entered medical use in 1968 in the form of fentanyl citrate as a general anesthetic, and has since been used in chronic pain, palliative care and combat medicine.

The two other common pharmaceutical fentanyls are sufentanil and remifentanil. The former was first synthesized in 1974 and the latter was developed in the early 1990s. Sufentanil is the most potent prescription opioid currently available, and is the only one strong enough to displace buprenorphine and provide analgesia. Remifentanil, by contrast, has a faster onset and recovery time.

But these are not the fentanyls appearing in most drug deaths, which are known collectively as illicitly manufactured fentanyl (IMF) or clandestine fentanyl. Such drugs have a substantial chemical similarity to pharmaceutical fentanyls, going by names like 4-fluoroisobutyryl fentanyl, lofentanyl and valeryl fentanyl.

Each fentanyl has its own characteristics. For instance, a new study of 13 fatal overdoses in Michigan involving valeryl fentanyl found that blood samples from the same decedent tested both positive and negative for the drug. This indicates that valeryl fentanyl has unique pharmacokinetics, which could make it more difficult for medical examiners to detect in overdose cases.

Similarly, a recent study in Psychopharmacology on a fentanyl analog called cyclopropylfentanyl found that when the drug was given to rats it “displays much greater analgesic potency when compared to morphine, suggesting that cyclopropylfentanyl poses increased overdose risk for unsuspecting users.”

Fentanyl’s ‘Evil Cousin’

But in many cases, the lethal dose of an illicit fentanyl can only be guessed at. As Josh Bloom recently explained in the American Council on Science and Health, fentanyl’s “evil cousin” mefentanyl may be 35 times more potent than prescription fentanyl. Even worse, standard test strips for fentanyl are only modestly effective in detecting mefentanyl,

“It's a damn good thing that mefentanyl isn't one of the common fentanyls pouring into this country,” wrote Bloom. “Imagine if a much more potent analog of fentanyl (was) widely circulating in the US with no way to detect it preemptively. Nightmare.”

Further, how fentanyls combine with other drugs requires investigation. For instance, a recent report of a person smoking a drug mixture that combined a potent fentanyl analog with a psychostimulant suggests that drug traffickers are creating new designer drugs to reduce the risk of their customers dying from respiratory depression.

Some fentanyls are so potent and chemically complex that higher doses of the overdose reversing drug naloxone are needed. A new study in the International Journal of Pharmaceutics suggests that naloxone may have to be modified to work better against illicit fentanyls. The study authors are working on a derivative of naloxone named NX-90 that may have a better pharmacological profile.

So this is why the plural is essential. We need to know as much as possible about pharmaceutical fentanyl and its chemical cousins remifentanil and sufentanil in order to improve clinical care. And we need to know as much as possible about illicit fentanyls in order to detect them accurately and develop better overdose rescue drugs.

Last, we need to keep an eye out for new synthetic opioids like protonitazene and isotonitazene, which are emerging regularly and are even more potent than fentanyl.

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. 

Little Evidence Opioid Use by Children Leads to Addiction

By Pat Anson, PNN Editor

Healthcare providers have become more cautious in recent years about giving opioid pain medication to children, fearing that even short-term use could lead to a lifetime of addiction or even a fatal overdose.

But in a review at the University of Alberta, pediatric researchers found little evidence to support a link between short-term opioid use in childhood and opioid use disorder (OUD) later in life.

“We actually didn’t find a lot of evidence to directly answer our question,” said senior author Michele Dyson, PhD, assistant professor of pediatrics in the Faculty of Medicine & Dentistry and associate director of the Alberta Research Centre for Health Evidence.

“If opioids are used as indicated, they can be a safe and effective strategy for pain management,” she said. “In some cases, they really are part of the best treatment plan to manage a child’s pain.”

Dyson and her colleagues reviewed 21 observational studies involving nearly 50 million patients under the age of 18 who were exposed to opioids for less than 14 days. Most of the studies were considered low quality and did not look at the duration of opioid use.

One study did show a potential link between short-term exposure and later abuse. But researchers concluded the findings overall were not definitive because they did not specify duration of exposure or lacked a control group. Their findings are reported in the journal Pediatrics.

“There is limited evidence to determine if short-term therapeutic exposure to opioids in childhood is
definitively associated with future nonmedical opioid use or development of an OUD; however, this review suggests a link between lifetime therapeutic opioid use (unknown duration) and nonmedical opioid use. The existing evidence on risk factors for nonmedical opioid use or OUD after short-term therapeutic exposure is unclear,” researchers concluded.

Conflicting Advice

Whether opioid medication is appropriate for children is a controversial issue. Earlier this year, the World Health Organization (WHO) released new guidelines recommending that opioids only be used for children who are dying or seriously ill and not expected to recover.

Like the Alberta study, a WHO advisory panel found little good quality research on how to treat childhood pain, but recommended that children with chronic pain be treated with physical therapy and psychological interventions such as cognitive behavioral therapy.  

An international study in The Lancet came to a very different conclusion, warning that opioid prescribing guidelines intended for adults are being “inappropriately applied to young people.” Because of the stigma associated with opioids, researchers said childhood pain was often untreated or poorly treated, leading to chronic pain, disability and other negative consequences in adulthood.

“Health-care professionals, young people, and parents continue to hold misconceptions and believe myths about opioid use in pediatric patients, whereby the media depicts opioids as the villain and the underlying reason for substance misuse,” researchers said. “Opioids have their place in pediatric pain medicine.”

That finding is at odds with a 2018 warning from the U.S. Food and Drug Administration, which said that cough and cold medications containing opioids pose “serious risks” to children and should no longer be prescribed to patients younger than 18.

A recent study found that opioid misuse is relatively rare in U.S. adolescents and young adults. Less than 1% of those who filled an opioid prescription for the first time overdosed or developed opioid use disorder within the next 12 months.

The conflicting advice can be confusing to both parents and providers.

“Parents see stories about overdoses in the news and are afraid for their children, while physicians and prescribers are also worried because they don’t know what the evidence is,” says Dyson. “Health-care providers don’t want to cause harm, and at the same time, they still want to be able to treat pain appropriately.”

Dyson and her team at the University of Alberta have developed a series of infographics to help physicians, parents and young people recognize that opioid pain relievers are sometimes needed.

One such graphic plainly states: “Opioids don’t have to be scary!”

View fullsize

UNIVERSITY OF ALBERTA INFOGRAPHIC

“While we can’t say for sure that a short-term prescription for pain is linked with misuse, there is some evidence that that could happen,” she explained. “There is likely some risk, but it needs to be balanced with the harms of stigmatizing opioid use and under-treating pain, which comes with its own significant short- and long-term consequences.”

Are You in Palliative or Curative Care?

By Dr. Forest Tennant, PNN Columnist

If you are in medical treatment for a chronic disease, you are either in curative or palliative care. Every patient with intractable pain syndrome (IPS), their family and physicians need to be very clear as to which category they are in.

A major reason that IPS patients can’t get the help they need is because they have not made the determination and been declared to be in palliative care. If you are not in palliative care, you may be restricted from obtaining certain drugs, dosages and financial benefits you need for your well-being. 

What is Curative Care?

Curative care is treatment that is focused on resolving a specific disease or disorder that is causing symptoms such as pain, fatigue, depression or physical impairments. Treatment can be directed either at total or partial cure of the disease or disorder.

What is Palliative Care?

Palliative care is symptomatic treatment to provide relief and quality of life to someone with an incurable condition. Palliative care will also hopefully prevent an incurable disease or disorder from worsening and causing further complications.

There are two reference books published for physicians so they can quickly look up the latest on diagnosis and treatment.  Their definitions of palliative care are given here to help all parties know which care -- palliative or curative --- best fits any given patient.

“Palliative care is medical care focused on improving quality of life for people living with serious illness. Serious illness is defined as a condition that carries a high risk of mortality, negatively impacts quality of life and daily function and/or is burdensome in symptoms, treatments and caregiver stress.” -- Current Medical Diagnosis and Treatment

“Palliative care is treatment that is focused on pain and symptom management as well as quality of life for patients and their families. It can be rendered at any point in the course of treatment of illness, whether that illness is life threatening or not.” – Current Therapy

The World Health Organization defines palliative care as “prevention and relief of suffering in adults or pediatric patients and their families facing the problems associated with life-threatening illness.”

Misconceptions About Palliative Care

There are many misconceptions about what qualifies a patient to be palliative care. Here are just some of the common misconceptions and fallacies:

• Must be at “end-of-life.” No! An incurable disease may occur at any age.

• Must be in a hospice. No!

• Must be on Medicare. No!

• Must be in a nursing home, assisted living or hospital. No!

• Must have cancer. No! Palliative care applies to any incurable disease.

• Must enroll in a program called “palliative” or with a “palliative care organization.” No!

• Must go to a doctor who specializes in palliative care. No!

• Palliative care requires the patient to have a permit or certificate. No!

Even though there are some physicians and programs that specialize in palliative care, any MD or DO can declare a patient to be “palliative” and provide the necessary medication for relief of pain and other symptoms.

You may have to be declared to be in “palliative care” and have it stated in your medical record, so that you can obtain the medications and dosages to adequately relieve your pain. Federal guidelines specifically exempt palliative care patients from a recommendation that daily opioid doses not exceed 90 milligrams morphine equivalence (MME). If you have not been declared to be in palliative care and it isn’t in your medical record, your opioid dosage may be reduced. 

Presenting Your Case for Palliative Care

In order to obtain proper care and necessary medications in today’s healthcare system, you will likely need to be declared “palliative” by one of your personal physicians. This declaration will need to be recorded in your medical record and all concerned parties informed of it. Your pharmacy, insurer, laboratory and other healthcare providers should all be told that you are in palliative care.  

Most IPS patients need palliative care and meet the necessary requirements to be declared as palliative. One of your doctors needs to simply write into your medical record the name of your incurable disease, and that your treatment will focus on symptom management, comfort and quality of life. There is no requirement to state how long you may live.

The only required documentation is a written chart note in your medical record by a licensed physician in your state. They will need to state the specific name of your incurable disease and that you are in palliative care.

Every IPS patient and family needs to determine whether their treatment needs to be palliative or curative.  While everyone would like a cure, this may not be practical or possible.  What evidence or experience tells you that you can achieve a cure?  It may be depressing to recognize that a complete cure is not possible, but you must face reality.

Keep in mind that an incurable disease and pain doesn’t have to keep you from having a meaningful, productive and good quality of life. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here. The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Stem Cells Could Help Diabetics Produce Their Own Insulin

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

— Eelco de Koning, MD

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

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

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

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

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

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

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

Patients and Doctors Finally Talking About Medical Cannabis

By Pat Anson, PNN Editor

Communication is important in every relationship, especially between doctors and patients. And a new survey suggests that the stigma that has long kept cannabis a dirty secret in the exam room may finally be disappearing.   

The survey of 445 healthcare providers who treat chronic pain found that 72% of them have patients who requested or asked about medical cannabis in the last 30 days. Patients asked about cannabis far more often than other alternative pain treatments, such as acupuncture (37%), physical therapy (13%) and massage (10%).

The online survey was recently conducted by Cannaceutica, a healthcare company developing a line of cannabis products to treat pain. A variety of providers participated in the survey, including general practitioners, pain management specialists, neurologists, rheumatologists, and nurse practitioners.

People weren’t always so willing to talk to healthcare providers about cannabis, fearing they’d be seen as pot heads or even be dropped as patients. National surveys conducted in 2018 and 2019 found that less than 40% of patients told their doctors about their cannabis use.  

More patients are talking about cannabis today, and more doctors are willing to listen. The vast majority of providers (81%) in the Cannaceutica survey believe cannabis will play a role in the future management of chronic pain, but only one in four are likely to recommend it now. The primary factors holding them back are legal and regulatory issues, and the lack of good quality cannabis research.

Medical cannabis is legal in 36 states, but remains illegal at the federal level. If cannabis were legalized federally, 74% of providers said they would be likely to recommend it to a patient.

To increase their comfort level about recommending cannabis, providers want to see more research and documentation about cannabis as a pain treatment. Nearly two-thirds (64%) said patients were their main source of information about cannabis, followed by the internet (44%) and medical journals (40%).

Over half the providers surveyed said current treatment options are insufficient to treat chronic pain (56%) and that they were actively seeking alternatives (58%) for their patients. It’s worth noting that pain management specialists were most likely to say current treatments are inadequate (59%) and that they were seeking alternative treatments (66%).  

Clinical Trial Seeks Volunteers

Cannaceutica is currently enrolling chronic pain patients in a clinical trial to test the safety and efficacy of its cannabis capsules, which contain a blend of tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as the cannabinoids cannabichromene (CBC) and cannabigerol (CBG). A recent study found that CBG boosts the potency of cannabis products used to treat chronic pain, depression, insomnia and anxiety.

The observational study is being led by University of California, Irvine researcher Dr. Marcela Dominguez. She and her team hope to enroll 107 patients in the trial, which is expected to last 14 to 16 weeks. They’re looking for people who have experienced pain for at least three months, have tried at least two different medications, and are not currently using cannabis. Patients with fibromyalgia or cancer pain are not eligible to participate.

If you would like to volunteer or get more information in the study, click here.

Rare Disease Spotlight: Valley Fever

By Barby Ingle, PNN Columnist 

As the final article in my series on rare diseases, I am going to cover something that has been impacting my life for the past 2 years and 25 days – coccidioidomycosis --- otherwise known as Valley fever. This is a health challenge that has been difficult and longer lasting than typical for a patient like me. I have headaches, chest pain and feel exhausted.

Tests show that I am still positive for Valley fever, both the active fungal infection and the antibodies my body produces to fight it. Over the past few weeks, I feel more pressure in my lungs, as if Valley fever pneumonia is returning. I am more exhausted than ever and have skin blisters again. I liken them to shingles, as I have had them multiple times over the past few years and it usually happens during periods of stress.

I took an antiviral, but maybe it is the Valley fever that is showing itself again as my breathing decreases. I can tell this by feel, as well as testing my blood oxygen levels and heart rate hourly over the past week. My coughing and shortness of breath have also increased.

Is this a new exposure or just the same old, same old? I have a close family member going through Covid currently and have been extremely careful not to get it, but I wonder. I have been tested for Covid 5 times now over the past 2 weeks with 3 home tests, a rapid test and a PCR test. All of these were negative, for which I thank God. But the symptoms of Covid and Valley fever seem to be similar.  

BARBY INGLE

When I first got the Valley fever in 2019, PNN did an article about what I was going through and the growing number of cases in the Southwest. Little did I know I would still be dealing with Valley fever more than 2 years later.

My lung specialist told me it would take about one year to get over it. The variable we did not know at that time was that I was allergic to the one medication that is invented specifically for coccidioidomycosis.

Since my diagnosis, I have been extremely tired -- more than I was with any of the other chronic and rare diseases I live with. I do not know if this is a new infection or if my immune system is compromised by all that I live with. I do know I am tired. All of the time.

It has also put my thinking and ability to handle pain into a new view. I am now very mindful of my breathing, getting oxygen appropriately, and any tingling sensations. That is the feeling I get when my oxygen levels are low. I used to worry more about the burning fire pain from RSD. That is still there and is constant, too. However, if I can’t breathe, the pain doesn’t matter as I won’t be able to live. 

How does one get coccidioidomycosis? The coccidioides fungus that causes it is found in soil of the desert Southwest and causes infection when inhaled. You can get it simply by breathing in microscopic fungus spores. Even our pets, especially dogs, can get Valley fever. It is not passed from human to human, although if you breathe the same air, you may see a cluster of people with it.

My husband Ken was tested for Valley fever after I developed it. His lungs show that he did have it, though he has a great immune system and showed no signs or symptoms. His body just beat it.

For people like me with suppressed immune systems, the risk is high for complications and severe symptoms if we become infected. I was actually misdiagnosed at first because Valley fever does resemble a flu with fever, cough, chills and chest pain. Once it turned into pneumonia and I was treated for a bacterial infection, it was figured out.

Ironically, my lung specialist thought that Ken and I probably got it from driving with the car windows down for fresh air. Valley fever cases spike when summer monsoons hit and cause dirt devils, and after earthquakes when fungal spores are kicked up into the atmosphere.

Worldwide and nationally, Valley fever is considered a rare condition. But in the U.S. Southwest and northern Mexico it is more common. If you are visiting the Southwest or live here, it is a condition you should know about and understand. The sooner you can take action against it or not be exposed to it, the better. Arizona, where I live, accounts for about two-thirds of the cases each year.   

Most infections last for a few weeks or months, but some patients like me can have symptoms that last longer. Because I experienced such a severe case at the start, I have long-term damage in my lungs and will likely continue to have challenges with my breathing and energy.  

I hope that you have enjoyed my series on rare diseases and have found the information educational, useful and motivating. I would love if more people understood the 7,000 plus rare diseases just a little better. I still have a long way to go to understand and learn about them. I have only scratched the surface. It has given me a better understanding of the diversity in conditions, the similarities that patients with rare diseases experience, and an empathy for those fellow patients who I advocate for as often as I can.

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

A Promising Stem Cell Therapy for Back Pain

By Gabriella Kelly-Davies, PNN Columnist

Just before sunrise on Christmas Eve last year, a delivery van from our local fish market left a bulky box of fresh prawns, oysters and lobsters on our doorstep for Christmas Day celebrations.  

Sleepily bending over, I picked up the box, unaware it was packed to the brim with enormous blocks of ice to prevent the seafood from succumbing to Australia’s stifling summer heat. As I lifted the box from the doormat, I felt a sharp pain like an electric shock run down the back of my left leg and pins and needles explode in my left foot.  

Fast forward to now, and the pain and pins and needles sensation are constant, especially when I sit to write. Like millions of other people, I have chronic lower back pain, the leading cause of disability worldwide. And like them, I too want the pain to go away without surgery.  

Two weeks ago, my pain specialist injected cortisone into my spine, reducing the pain enough to allow me to sit for meals and do a little writing. But he warned I would most likely need surgery at some point. The neurosurgeon agreed, suggesting microdiscectomy was my only option.  

As a former physiotherapist, I know that a lumbar discectomy can relieve the symptoms of nerve compression, but it doesn’t reverse the underlying degeneration of the intervertebral disc. This is why up to one third of patients continue to experience back pain after surgery and some require further operations.

In my search for non-surgical treatments, I read an article about Australian research that has led to the development of a new stem cell therapy to treat back pain. Professor Tony Goldschlager, who leads the study, is a neurosurgeon who advocates for the use of minimally invasive spinal surgery. He heads up a research team at Monash University in Melbourne that is part of the Monash Health Translation Precinct (MHTP).  

Goldschlager started his stem cell research 15 years ago. He and his team developed the stem cell therapy in the laboratory, then spent years testing it in preclinical models. The results of several studies revealed that the therapy was safe and effective. After completing these studies, the researchers began human clinical trials, testing the ability of stem cells to regenerate the intervertebral disc and reduce back pain.  

“We’ve had success both in preclinical and clinical studies of being able to restore structure and function of the disc,” Goldschlager told me. “This reduces pain and improves quality of life for patients.” 

Phase Two clinical trials saw a significant number of patients report reduced back pain for up to two years after a single injection. Phase Three trials are almost complete and while Goldschlager hasn’t received all the results from overseas studies, the data he has seen so far is promising. He is hopeful the new treatment— a single injection — will be available in two years after the final round of clinical trials concludes. 

“What excites me is that we might be able to prevent surgery all together and regenerate the disc. Most of the current treatments don’t address the underlying problem. But the stem cell injection reduces the inflammation and stimulates a regenerative process in the disc, removing the source of back pain. The stem cells can become new disc-like cells and replenish the damaged disc cells,” explained Goldschlager. 

During the last 15 years, Goldschlager and his team have published the results of their studies in peer-reviewed journals such as Spine, Nature Outlook and the Journal of Neurosurgery. In 2015, they published an extensive review of the use of stem cell therapies in lumbar disc disease. 

New Era in Medicine

While the use of stem cells heralds the dawn of an exciting new era in modern medicine, it also raises several ethical and safety concerns. Critics say many stem cell therapies are unproven, and others believe it is unethical to destroy human embryos during research or create new embryos specifically for research. 

Goldschlager is acutely aware of these concerns and in 2010 as a neurosurgery registrar, worked in a research team that published an article on the ethics of using stem cell therapies in patients with spinal cord injuries. He says the therapy his team has developed doesn’t raise ethical concerns because it is based on a proprietary adult stem cell technology from Mesoblast, an Australian biotechnology company.

The cells are derived from the bone marrow of healthy young adults who have given informed consent. Young adults are selected because the number of stem cells in our bodies reduce as we age. The cells of older people are also less effective at repairing damaged tissues and organs.

Commercial stem cell clinics usually harvest the fat, muscle or cartilage cells of their patients, process the cells in a centrifuge, then inject them back into the same patient’s body. This yields a mixed population of cells with a small and inconsistent number of stem cells. Adults of all ages are offered this treatment, even though it might not work for older patients because their stem cells are not as plentiful or robust as those of younger ones. These treatments can cost thousands of dollars, are often ineffective, and come with a heightened risk compared to a pure, tested proprietary off-the-shelf product.  

Another reason for caution is that some of the clinicians who provide stem cell treatments lack sufficient training and accreditation, increasing the risk of safety and efficacy issues. It is critically important for patients to check the qualifications of clinicians who offer stem cell therapies and to understand how the cells used at these clinics are created. The therapy should have been through rigorous clinical trials to demonstrate safety and efficacy.  

While new stem cell treatments offer hope to millions of people who live with degenerative spinal conditions, they are not a “miracle cure.” Still, I hope I’ll have the option of trying Professor Goldschlager’s technique once it is available.

Gabriella Kelly-Davies lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

People in Pain Fight What Others Can’t Understand

By Carol Levy, PNN Columnist

“We are so fond of one another, because our ailments are the same.” Jonathan Swift.

That does not apply to those of us with chronic or intractable pain. Our “ailments” are different. Very different. Painful conditions caused by genetics, trauma, medical error or sheer bad luck. Many healthy people don’t know such pain can exist.

In the 1980's, organ transplant rejection was thought to be psychological. Then they learned that it is not in the mind. It is the body doing the rejecting.

Forty years later, many doctors still believe chronic pain is in the psyche. Hopefully, more are accepting that the mind is involved in chronic pain and helps determine how we respond to it, but it’s not where the pain originates.

As difficult as it is for us to accept persistent pain and the resultant disabilities, it makes it even harder when doctors, family, friends and colleagues say, “Oh, c'mon. It's not that bad. You just think it is. So you can think it into being better.”

Mindfulness, relaxation techniques and meditation are helpful -- to the mind. They help some of us deal with the pain, but most still need the benefit of opioids and other pain medications, treatments and physical therapy.

“I don't want my pain and struggle to make me a victim. I want my battle to make me someone else's hero.” Unknown author.

How often do we hear that? First usually comes the praise: “You are a true pain warrior.” Then the gut punch: “Your pain and struggle are such a good example to others who suffer. You should be grateful. That’s why you have the pain, to be an example.”

I'm sorry, but I don't want to be in pain every day so someone else can learn from my fight. It is a nice side benefit, but it is not why I fight the pain.

Chronic pain does make us different from others. We talk about it a lot, online and elsewhere. Cancer, diabetes, heart disease and other well-known illnesses -- people know and understand them. But Ehlers Danlos, CRPS, trigeminal neuralgia, arachnoiditis and other names too long to list are still the stranger in the room.

It is a struggle for us every day. We fight what others can't and don't want to understand.  Because it is a feared ailment once they know it exists.

Our fight is with us at all times, in whatever we do or try to do. It is daunting.

“Promise me you'll always remember: You're braver than you believe, and stronger than you seem, and smarter than you think.” A.A. Milne

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.