Opioid Overdoses Rise in Intensive Care

By Pat Anson Editor

Opioid overdose deaths in intensive care units (ICUs) have risen sharply in recent years -- primarily due to heroin --  according to a large new study involving 162 U.S. hospitals in 44 states.

The research findings, published in the Annals of the American Thoracic Society, analyzed data from over four million ICU patients from 2009 to 2015. Of those, 21,705 were patients who overdosed on opioids, most commonly heroin. Deaths from overdoses averaged 7 percent during the study period, but rose to 10 percent by 2015.

“Although our data are not definitive, they suggest that overdoses from heroin, rather than prescription opioids, appear to be a major contributor to the rise in critical care mortality for this population,” wrote lead author, Jennifer Stevens, MD, an associate director of the medical intensive care unit at Beth Israel Deaconess Medical Center and an assistant professor of medicine at Harvard Medical School.

“Not only did the number of opioid-related overdose patients requiring ICU care increase above and beyond the increasing supply of critical care admissions, the mortality among this population increased as well, leading us to estimate that there was a near doubling of ICU deaths.”

Researchers say ICU patients admitted for a heroin overdose were significantly more likely to die than those who overdosed on prescription opioids. Mortality was “not significantly associated” with overdoses linked to prescription painkillers.

The study also found that overdose patients admitted to ICUs required increasingly more sophisticated and costly intensive care, such as high-cost renal replacement therapy or dialysis. The cost of caring for these patients increased from $58,517 to $92,408 during the study period.

"This study tells us that the opioid epidemic has made people sicker and killed more people, in spite of all the care we can provide in the ICU, including mechanical ventilation, acute dialysis, life support and round-the-clock care," said Stevens.

Among the opioid overdose patients, 25 percent experienced aspiration pneumonia, 15 percent rhabdomyolosis (release of dead muscle fiber into the bloodstream), 8 percent anoxic brain injury and 6 percent experienced septic shock. Ten percent of the patients who overdosed needed mechanical ventilation. ICU’s in Massachusetts, Indiana and Pennsylvania had substantially higher overdose death rates.

A new study this week found the number of Americans who died from opioid overdoses – particularly from heroin – is significantly higher than previously reported. Researchers at the University of Virginia refined the overdose data from 2014 death certificates and estimated that overdose death rates nationally were 22 percent higher for heroin. Deaths involving heroin were substantially underreported in Pennsylvania, Indiana, New Jersey, Louisiana, and Alabama.

"The pace of the opioid epidemic continues to increase," said Stevens. "Those of us who work in hospital intensive care units need to make sure we have the tools we need to help patients with opioid use disorders when they are at their sickest, because there doesn't appear to be any end to this epidemic in sight."

Brain Scans Link Fibromyalgia and Pelvic Pain

By Pat Anson, Editor

Fibromylagia and urological pelvic pain would seem to have little in common. The former causes widespread body pain, while the latter is marked by chronic inflammatory pain in the bladder or prostate.

But researchers at the University of Michigan have stumbled upon something that both conditions share – besides being difficult to treat.

While examining MRI brain scans of over 1,000 participants enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network  -- also known as the MAPP study – they found that people with fibromyalgia or chronic urological pelvic pain both have increased “gray matter” in their brains. Gray matter is tissue in the brain that helps transfer signals between nerves.

"Interestingly, when we put these individuals into the brain imaging scanner, we found that those who had widespread pain had increased gray matter and brain connectivity within sensory and motor cortical areas, when compared to pain-free controls," says Richard Harris, PhD, an associate professor of anesthesiology and rheumatology at Michigan Medicine.

Harris and colleagues want to know if widespread pain, thought to be a marker of centralization in the nervous system, actually originates in the brain. So it was a bit of a surprise to find additional gray matter in the brains of people with urological pelvic pain, a condition that can be caused by interstitial cystitis or chronic prostatitis.

"What was surprising was these individuals with widespread pain, although they had the diagnosis of urological chronic pelvic pain, were actually identical to another chronic pain disorder: fibromyalgia," said Harris.

In addition to the MRI scans, study participants were also asked to draw on a body map where they were experiencing pain. Many of those with pelvic pain indicated they had widespread body pain.

"This study represents the fact that pelvic pain patients, a subset of them, have characteristics of fibromyalgia," Harris says. "Not only do they have widespread pain, but also they have brain markers indistinguishable from fibromyalgia patients."

Harris hopes the study will lead to new ways of treating chronic pain -- as there might be similarities across pain conditions if both show widespread pain.

"We think that this type of study will help treat these patients because if they have a central nerve biological component to their disorder, they're much more likely to benefit from targets that affect the central nervous system rather than from treatments that are aimed at the pelvic region," Harris said.

Study Finds Rain Not Linked to Joint Pain

By Pat Anson, Editor

The debate over weather’s influence on pain is heating up again, with the release of a new study that showed warmer temperatures -- not rainy conditions -- are associated with an increase in online searches about joint pain.

The apparent increase in knee and hip pain may be due to increased outdoor physical activity, according to researchers who reported their findings in PLOS ONE.

Investigators used Google Trends to analyze how often people used Google’s search engine to look up words and phrases associated with hip pain, knee pain and arthritis. Then they compared the results with local weather conditions at 45 U.S. cities. The weather data included temperature, precipitation, relative humidity and barometric pressure - conditions previously associated with increases in musculoskeletal pain.

Researchers found that as temperatures rose, Google searches about knee and hip pain rose steadily, too. But knee-pain searches peaked at 73 degrees Fahrenheit and became less frequent at higher temperatures. And searches for hip-pain peaked at 83 degrees and then tailed off.

Surprisingly, rain actually dampened search volumes for both knee and hip pain.

"We were surprised by how consistent the results were throughout the range of temperatures in cities across the country," said Scott Telfer, a researcher in orthopedics and sports medicine at the University of Washington School of Medicine.

Searches about arthritis, which was the study's main impetus, had no correlation with weather conditions.

"You hear people with arthritis say they can tell when the weather is changing," he said. "But with past studies there's only been vague associations, nothing very concrete, and our findings align with those."

What do the findings mean?

Because knee and hip-pain searches increased until it grew warm, and rainy days tended to slightly reduce searches for hip and knee pain, the researchers speculate that changes in outdoor physical activity may be primarily responsible for those searches.

"What we think is much more likely explanation is the fact that people are more active on nice days, so more prone to have overuse and acute injuries from that and to search online for relevant information,” Telfer said, adding that web searches are often the first response people have to health symptoms.

Researchers in Australia recently reported that cold, rainy weather has no impact on symptoms associated with back pain or osteoarthritis. Warmer temperatures did slightly increase the chances of lower back pain, but the amount of the increase was not considered clinically important. 

A previous study on back pain and weather by The George Institute for Global Health had similar findings, but received widespread criticism from the public, a sign of just how certain many people are that weather affects how much pain they feel.

“I know it is going to rain or have a thunderstorm before the weather person announces it on the news,” says Denee Hand, who suffers back pain from arachnoiditis, a chronic inflammation of the spinal membrane. She says the pain spreads down to her toes when the weather changes. 

“It is like my nervous system and muscles react to the coming weather and finally I get pain that feels like the tops of both my feet are being crushed,” she said in an email to PNN. “I have compression of the spinal cord with nerve damage to my nerves from the scar tissue and when the weather changes the scar tissue presses down against the damaged nerves.”

Researchers at the University of Manchester recently ended a study involving thousands of people who used smartphone apps to report their pain levels, giving investigators the ability to compare the pain data with real-time local weather. Researchers are now analyzing the database compiled over the last 15 months and will release their results next spring.

Insurance Claims Climb for Lyme Disease

By Pat Anson, Editor

Private insurance claims with a diagnosis of Lyme disease have soared in the U.S. over the past decade, according to a new report by FAIR Health, a nonprofit that tracks healthcare costs and insurance trends.

Lyme disease is a bacterial illness spread by ticks. It can also lead to other chronic pain conditions such as joint and back pain, chronic fatigue, fibromyalgia and neuropathy.

Fair Health analyzed a database of 23 billion private insurance claims from 2007 to 2016, and found that claims with a diagnosis of Lyme disease increased by 185 percent in rural areas and 40 percent in urban areas.

A recent CDC study also found the number of Lyme disease cases increasing, with nearly 40,000 confirmed and probable cases in 2015.

"Lyme disease is growing as a public health concern,” said FAIR Health President Robin Gelburd

Although Lyme disease historically has been concentrated in the Northeast and upper Midwest, the FAIR Health study suggests that it is spreading geographically. In 2007, insurance claims with diagnoses of Lyme disease were highest in New Jersey, Rhode Island, Connecticut, Massachusetts and New York.

By 2016, the top states were Rhode Island, New Jersey, Connecticut, North Carolina and New York -- with the emergence of North Carolina suggesting significant expansion to a new region.

Summer is the peak season for Lyme disease, with insurance claims more common in rural than in urban settings, according to the FAIR Health report. In the winter and early spring (December through April), claims involving Lyme disease were reported more often in urban than rural settings.

Age is also a differing factor in rural and urban environments. In rural settings, claims with Lyme disease diagnoses were more common for middle-aged and older people. Patients aged 41 years and older accounted for nearly two-thirds of the rural diagnoses. In urban populations, younger individuals with Lyme disease accounted for a higher percentage of claims.

Lyme disease is usually treated with antibiotics, but some patients experience complications that lead to Lyme disease syndrome (PTLDS), with long-term symptoms such as fatigue, muscle and joint pain and cognitive issues. Autoimmune diseases have also been associated with chronic Lyme disease.

Left untreated, Lyme disease can lead to serious chronic conditions, as Sarah Elizabeth Hirschle shared with us recently.

For patients with a Lyme disease diagnosis, FAIR Health reported the most common subsequent diagnoses were:

• Joint pain (dorsalgia, low back pain, hip and knee pain)
• Chronic fatigue  
• Soft tissue disorders (myalgia, neuralgia, fibromyalgia)
• Hypothyroidism

lyme disease rash

Early symptoms of Lyme disease include fever, chills, headaches, fatigue, muscle and joint aches, and swollen lymph nodes. A delayed rash often appears at the site of the tick bite. The rash grows in size and sometimes resembles a bulls-eye.

To see some tips from the CDC on how to avoid tick bites, click here.

The Importance of Understanding Research

By Janice Reynolds, Guest Columnist

Almost daily we are told that a study shows this or research shows that, a physician makes claims based on research, or the news media blaring “New Study Shows.” 

Even worse, more and more frequently we are seeing providers, government and the media basing their opinions or actions on poor evidence -- or many times the total lack of it.  I have a tee shirt which says: “Show me the evidence and critical thinking.”

It is time for people in pain as well as their advocates to understand research studies and hold accountable those that are cited.

Evaluating research is a little complicated and time consuming, but it is something every medical person needs to do.  More importantly, the media needs to justify their reliance on research and identify that what they are saying is true, rather than something totally lacking in validation and objectivity (which unfortunately is most often the case). 

After all, the media claim to do careful research before doing a story. Politicians should also have accountability for objective truth.

As people living in pain, our arguments and comments are more effective if we show that we know what we're talking about.  It may not change someone's mind if they are opiophobic or dislike and distrust people in pain, but it’s important to try.

I’ve made repeated requests to the Portland Press Herald to give me the citations for their claim that “studies have shown conclusively that opioids not only don’t work for chronic pain but make it worse.” I haven’t changed their minds, but it is ammunition in the battle for actual truth.

These are some of the terms the public and people in pain need to understand:

Correlation and causation: Probably the most important.  Just because something happens at the same time, does not mean one thing “causes” the other.    My husband teaches statistics at a university and the example he uses is when the number of new boat licenses increases the number of manatees being killed. This does not mean boat licenses kill manatees.  This correlation means causation thing is rampant in media stories about pain.

Anecdotes and surveys:  An anecdote is an account not necessarily true or reliable, because it is based on personal experience rather than facts or research.  For every anecdote, there are often many more which tell a totally different story. An example would be: "My son died of an opioid overdose. We have to stop these drugs from killing people." Any death is tragic, but opioids do not in themselves kill people. 

Surveys also rely on someone’s self-reporting.  The one used extensively by the media and politicians is that 3 in every 4 heroin addicts got their start taking prescription opioids. That particular survey relied on addicts to tell the truth, did not not include addicts outside of treatment, and most importunately did not include millions who have taken opioids for pain and never even touched heroin.  Surveys and anecdotes are worthless as evidence.   

Case studies:  These are things that happened to a person, group or situation at a single time and/or place; i.e. a case history.  The CDC makes use of case studies to “prove” in their seminars the correctness of their opioid guidelines.  Case studies are of interest, but are not valid evidence for the same reasons anecdotes are not.

Data mining: This is the process of collecting, searching through, and analyzing a database to discover patterns or relationships. In our case, it usually means they have gone through death certificates, insurance records and the like.  Once again, this is not a source of evidence as there is no way to verify the validity of the data, as well as other confounding factors.  Data mining is the CDC’s favorite method and it has been shown to be highly inaccurate. It does not have a place in medicine, except to develop insights and lead to actual research.

Statistics: These by themselves do not mean much. Researchers need to use the appropriate statistical analyses before publishing them.  Medical providers, media and politicians need to acknowledge what analysis method was used and what the outcomes were.

Qualitative vs quantitative: Qualitative research gathers information that is not in numerical form. For example, diary accounts, questionnaires, case studies and anecdotal accounts are used to gain an understanding of underlying reasons, opinions and motivations. Qualitative data is typically descriptive data and as such is harder to analyze than quantitative data. It can never be “proof.”

Quantitative research looks at numbers, it is the “hard” science. Quantitative research is used to quantify the problem by way of generating numerical data that can be transformed into useable statistics that can be evaluated.

Objectivity: Objectivity means being aware and honest about how one's beliefs, values and biases affect the research process. This also applies to the reviewing, reporting, and selection of research.  The media especially lacks objectivity in their reporting of all issues related to people in pain and the “opioid addiction epidemic”.

Method:  How the study was done; meta-analysis, random controlled trials, non-random controlled trials, survey, cohort or case controlled study, or even expert opinion. The latter is only acceptable when no other research exists on the subject.

Sampling: The number of participants and who they were. A small number has a lower strength of evidence.  My favorite example of a “who” was a study done which claimed to show analgesics caused people to be homicidal.  Their sampling took place in a prison where all the participants were murderers!  Doesn’t take a rocket scientist to figure out this was biased.

Strength of evidence: This is probably the most important term when it comes to research.  There are many different tables used (easy to Google) that show a hierarchy of what is strong evidence, what is weak and what is non-existent.  Even the CDC recognized the evidence for their opioid guidelines was weak to non-existent. Most studies on the opioid epidemic or people in pain are inherently weak because the evidence is so poor.  

Proof:  Research seldom ever provides “proof.”  If multiple studies come up with the same results, then some might call it proof; however it is safer to say “likely.”  When talking about pain, medications, interventions or even addiction, the word “proof” should be off the docket.

Critical thinking: Critical thinking is the identification and evaluation of evidence to guide decision making. Another definition is making reasoned judgments that are logical and well thought out, a way of thinking in which you don't simply accept all arguments and conclusions you are exposed to, but rather question such arguments and conclusions. 

Those who are prejudiced and biased against people in pain or opiophobic rarely use any critical thinking skills at all.  In fact, after a comment I had made on a newspaper article, someone assassinated my character by saying my head was filled with mashed potatoes and I lacked any critical thinking skills whatsoever.  There was more and it was pretty funny.  This unfortunately is characteristic of the media, politicians and general public. No matter what we say or how truthful our comments, they will not hear. 

Evidence based: This means looking at best available clinical evidence from methodical research.  The word term is thrown around lightly and unless you have the actual “evidence” to back it up, it is meaningless. 

Several years ago, I was part of the original Pain PEP (Putting Evidence into Practice) team for the Oncology Nursing Society. We studied pharmaceutical interventions for nociceptor and neuropathic pain in the adult cancer patients. It took us two years to evaluate recent guidelines and research studies, and to write our guidelines based on the strength of the evidence. If you say something is “evidence based,” be prepared to show it.

One last comment on the issue of research and pain management: There are integral difficulties in pain research as people vary in their reaction to pain, the cause of their pain, and how they respond to treatment. Any research that uses the term “chronic pain” is already working with a false premise because there are so many different types of pain that are persistent.  Any research that looks at a “class” of medication such as opioids or antidepressants is also employing a false basis as well.

Pain management is an art and a science, and any attempts to standardize it will only harm people in pain.  

Janice Reynolds is a retired nurse who specialized in pain management, oncology, and palliative care. She has lectured across the country at medical conferences on different aspects of pain and pain management, and is co-author of several articles in peer reviewed journals. 

Janice has lived with persistent post craniotomy pain since 2009.  She is active with The Pain Community and writes several blogs for them, including a regular one on cooking with pain. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Proove Biosciences Linked to Fraud Investigation

By Pat Anson, Editor

A genetic testing company in southern California has been linked to a nationwide crackdown on healthcare fraud that resulted in criminal charges being filed against hundreds of doctors, nurses and medical professionals.

Among the defendants are three individuals affiliated with Physicians Primary Care of Jeffersonville, Indiana, who are accused of unlawfully dispensing oxycodone, hydrocodone and other opioid medications to patients without a legitimate medical need.

The charges also allege that Jeffrey Campbell, MD, and nurse practitioners Mark Dyer and Dawn Antle "caused Proove Bioscience, Inc., a genetic lab company, to falsely and fraudulently bill various health care programs for genetic tests administered to Physicians Primary Care patients that were not medically necessary and never interpreted."

Proove Biosciences is not formally charged in the grand jury indictment, which was unsealed yesterday in the U.S. District Court of Kentucky in Louisville. In an emailed statement to PNN, Proove's founder and CEO said the company cooperated with authorities and terminated its contract with Dr. Campbell when it first learned of the investigation in 2014.

"Since then, Proove has cooperated with both the FBI and US Attorney’s office on this case," said Brian Meshkin. "With regards to tests being 'medically necessary', Proove received written and signed determinations of medical necessity supporting the tests ordered and billed to insurance carriers just like every other laboratory which requires such a determination on a test requisition form. Thus Proove operated appropriately and consistent with usual and customary practices."

As PNN has reported, Proove’s headquarters in Irvine, California was raided by FBI agents last month, along with doctors affiliated with Proove in California, Florida and Kentucky. At the time, the FBI would only say the raids were part of a healthcare fraud investigation.

STAT News reported in February that the FBI and the Inspector General for the Department of Health and Human Services (HHS) were investigating possible criminal activity at Proove. Former and current employees interviewed by the FBI said agents were focused on illegal kickbacks to doctors who encouraged patients to take Proove’s DNA tests. Physicians reportedly could make $144,000 a year in kickbacks that were called “research fees.”

"Proove has been subject to a handful of inaccurate stories,” Proove said in a statement last month.  “We can no longer ignore these false stories based on unreliable sources, and filled with erroneous accusations... spread by a few disgruntled former employees and consultants.”

In all, 412 defendants have been charged nationwide in what the Justice Department calls its “largest ever health care fraud enforcement action.” Most of the charges, according to prosecutors, involve the illegal distribution of painkillers and $1.3 billion in various billing schemes that targeted Medicare, Medicaid and TRICARE, a health insurance program for veterans and their families.    

Attorney General Jeff Sessions said nearly 300 health care providers were being suspended or banned from participating in federal health programs.

“Too many trusted medical professionals like doctors, nurses, and pharmacists have chosen to violate their oaths and put greed ahead of their patients,” said Sessions. “Amazingly, some have made their practices into multi-million dollar criminal enterprises. They seem oblivious to the disastrous consequences of their greed. Their actions not only enrich themselves often at the expense of taxpayers but also feed addictions and cause addictions to start.”

Proove’s ‘Peer Reviewed’ Studies

Proove Biosciences promotes itself as a “leader in personalized pain medicine” and claims its genetic tests have been proven effective in clinical studies at identifying medications that can best treat pain and other health conditions. Critics say most Proove studies are not peer-reviewed and one genetic expert told STAT News the studies were “hogwash.”

Last month Proove claimed in a press release that 91% of patients in a peer-reviewed study reported pain relief after treatment changes prompted by its genetic tests. The press release said the study -- conducted by Katrina Lewis, MD, a member of Proove's medical advisory board who works at Benefis Pain Management Center in Great Falls, Montana – was “accepted for publication by the Journal of Addiction Research & Therapy.”

Not only has the study still not been published, but the journal’s publisher has been accused by the Federal Trade Commission (FTC) of deceiving researchers and readers about the true nature of its publications and peer review process.

According to the FTC complaint filed last August, OMICS International has created hundreds of "open access" online medical journals that publish articles with little or no peer review.

Researchers are also charged significant fees to get their articles published by OMICS, a "pay to play" policy that some consider unethical because it diminishes the quality of academic journals and the peer review process.

According to its website, OMICS publishes a dizzying array of over 700 online medical and scientific journals, ranging from the Journal of Hepatitis to the Journal of Yoga and Physical Therapy, "the official journal of Yoga Federation of Russia and the Hong Kong Yoga Association." 

“In reality, many of Defendants’ online publications do not adopt the rigorous peer review practices that are standard in the scholarly journal publishing industry,” the FTC complaint says. “In numerous instances, individuals who have agreed to serve as peer reviewers for Defendants either never receive any manuscripts to review or discover that, when they access the online manuscript review system to review their assigned articles, the articles have already been approved for publication. In addition, in numerous instances, consumers receive no edits or, at most, only stylistic edits before Defendants publish the work.” 

"As for the Journal of Addiction Research & Therapy, Proove can only speak to its experience with this particular journal and cannot comment on the allegations by the FTC," said CEO Meshkin. "Specifically for papers submitted to this journal, our R&D team and academic collaborators engaged in documented, extensive peer-review, received suggested edits and provided responses to the suggested edits to the manuscripts submitted for review and publication. Thus, Proove would certainly consider the publications accepted from Proove-affiliated authors in that journal to be 'peer-reviewed'." 

In March, OMICS published in the Journal of Addiction Research & Therapy a study by Proove which found that one of the company’s genetic tests could identify patients at high-risk of developing opioid use disorder. Proove said in a news release the study had been peer reviewed. 

In April, a second Proove study was published in Pharmacogenomics and Personalized Medicine, an online journal published by Dove Medical Press, another so-called predatory publisher that charges high fees to researchers to get their studies into medical journals.

"This is the first of many peer-reviewed publications over the next several months demonstrating the validity of Proove Opioid Risk (test), building on the existing published evidence," Dr. Svetlana Kantorovich, Proove's Research and Development director said in a news release.

Can Human Touch Relieve Pain?

By Pat Anson, Editor

Holding hands with a loved one is a simple and effective way to relieve some of their pain, according to the results of a novel study.

The key is to take advantage of an evolutionary trait that helped humans become social beings.

“Skin to skin touch is important for pain reduction, which may explain people’s preference for social touch. Moreover, touch activates reward circuits in the brain. Indeed, skin-to-skin touch has been shown to activate the reward system, which results in pain reduction both in animals and in humans,” wrote lead author Pavel Goldstein, a pain researcher in the Cognitive and Affective Neuroscience Lab at CU Boulder.

“It seems that this phenomenon has evolutionary roots. For example, non-human primates devote much more time to grooming than they actually need for hygiene reasons, resulting in endogenous opioid release, as well as pain and stress reduction.”

The new study, published in the journal Scientific Reports, is the first to explore interpersonal synchronization in the context of pain and touch.

Scientists have long known that people subconsciously sync their footsteps with the person they're walking with or adjust their posture to mirror a friend's during conversation. Studies have also shown that when romantic couples are simply in each other's presence, their cardiorespiratory and brainwave patterns sync up.

Goldstein came up with the idea of testing how synchronization affects pain after witnessing the birth of his daughter.

"My wife was in pain, and all I could think was, 'What can I do to help her?' I reached for her hand and it seemed to help," he recalls. "I wanted to test it out in the lab: Can one really decrease pain with touch, and if so, how?"

Goldstein recruited 22 healthy heterosexual couples, age 23 to 32, and put them through a series of tests aimed at mimicking that delivery-room scenario.

Men were assigned the role of observer, while the women were subjected to mild heat pain in the forearm for two minutes. As instruments measured their heart and breathing rates, the couples were put in three different scenarios: together but not touching; together holding hands; or sitting in separate rooms.

The couples’ heart and breathing rates synced physiologically while just sitting together. But when a woman was subjected to pain and her partner couldn't touch her, that synchronization ended. When he was allowed to hold her hand, their rates fell into sync again and her pain decreased.

"It appears that pain totally interrupts this interpersonal synchronization between couples," Goldstein said. "Touch brings it back.

“It is possible that the target of pain communicates back the analgesic effect of touch to the observer. Thus, the use of touch may improve the quality of non-verbal physiological communication between partners, especially when one of them feels pain, enabling the toucher to better project his empathy to the female partner and consequently have an analgesic effect.”

Goldstein's previous research found that the more empathy a man showed for a woman, the more her pain subsided during touch. The more physiologically synchronized they were, the less pain she felt. It's not clear yet whether the decrease in pain increased the synchronicity, or vice versa.

"It could be that touch is a tool for communicating empathy, resulting in an analgesic, or pain-killing, effect," said Goldstein.

Further research is needed to figure out how a partner's touch eases pain. Goldstein suspects interpersonal synchronization may play a role, by affecting a region of the brain that is associated with pain perception, empathy, and heart and respiratory function.

The study did not explore whether the same effect would occur with same-sex couples, or what happens when the man is the subject of pain. Goldstein hopes the research will help lend scientific credence to the notion that touch can ease pain.

The Consequences of Untreated Pain

By Roger Chriss, Columnist

Pain is an alarm signal requiring attention. Whether the pain lasts minutes or months, it demands a response. To ignore pain is to invite serious consequences, from burned skin or an infected wound to a damaged joint or dysfunctional nerve. It is for this reason that healthcare professionals ask patients where it hurts.

Recent research found the consequences of untreated pain go farther and deeper than are generally recognized:

• JAMA Internal Medicine reported that older people with chronic pain experience faster declines in memory and are more likely to develop dementia.
• Pain Medicine reported that osteoarthritis and related joint pain were strongly associated with memory loss.
• Arthritis Care & Research reported that pain severe enough to interfere with daily life was associated with an increased risk of mortality.

In the latter study, people who were “often troubled with pain” had a 29% increased risk of dying, and those who reported “quite a bit” or “extreme’ pain” had 38% and 88% increased risk of mortality, according to Medical Dialogues.

These results are new, but they are far from unique. For years researchers have been finding that chronic pain conditions have major long-term medical consequences.

In 2011, Pain Medicine reported that chronic pain “negatively impacts multiple aspects of patient health, including sleep, cognitive processes and brain function, mood/mental health, cardiovascular health, sexual function, and overall quality of life.”

In 2016, a study in the Journal of Pain Research reviewed the research literature and found that chronic pain “has significant consequences for patients, as well as for their families, and their social and professional environment, causing deterioration in the quality of life of patients and those close to them.”

However, awareness of the consequences of persistent pain conditions does not necessarily translate to effective care. As I wrote in a recent column, under treatment of pain is common, and the CDC opioid prescribing guidelines and groups like Physicians for Responsible Opioid Prescribing (PROP) are making things worse by demonizing opioids.

“The role of opioid analgesics has been distorted to the point where the word ‘oxycodone’ uttered in front of a patient in my palliative medicine clinic is met with raised eyebrows,” wrote Susan Glod, MD, in a recent op/ed on “The Other Victims of the Opioid Epidemic” published in The New England Journal of Medicine

Fear of a drug makes for bad medicine. Although opioid therapy includes possible cognitive side effects, so do anticholinergic muscle relaxants, which have been shown to increase the risk of dementia. Similar risks exist for many other treatment modalities.

Thus, effective management of chronic pain conditions requires expert care. The best results are often obtained in pain management programs that combine drug therapy with physical therapy or other modalities tailored to the individual patient’s needs.

Persistent pain is a danger sign that a major and potentially life-threatening toll is being exacted on the human body and mind. We do not have the luxury of ignoring or undertreating chronic pain conditions. Good pain management is one of the best ways to improve long-term outcomes and quality of life.

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.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Women Who ‘Catastrophize’ More Likely to Get Opioids

By Pat Anson, Editor

Women who complain or focus negatively on their pain – a psychological condition known as catastrophizing -- not only feel chronic pain more intensely, they are more likely than men to be prescribed opioids for the same condition, according to a new study.

"Our research underscores how psychological factors such as negative thoughts or emotions have the capacity to influence how we experience pain and the likelihood that someone will be taking prescribed opioids," said Beth Darnall, PhD, a clinical associate professor at Stanford University School of Medicine and senior author of the study published in the journal Anesthesiology.

"The findings suggest that pain intensity and catastrophizing contribute to different patterns of opioid prescribing for male and female patients, highlighting a potential need for examination and intervention in future studies."

Previous studies have found that pain catastrophizing can have a powerful influence on a patient’s sensory perception, and may magnify the intensity of chronic pain by as much as 20 percent.

In their retrospective study, Darnall and her colleagues analyzed clinical data from nearly 1,800 adult chronic pain patients at a large outpatient pain treatment center. Most of the patients said they were prescribed at least one opioid medication.

For women, pain catastrophizing was strongly associated with having an opioid prescription, even when there were relatively low levels of pain. Pain intensity was a stronger predictor of opioid prescriptions in men.

"Our findings show that even relatively low levels of negative cognitive and emotional responses to pain may have a great impact on opioid prescribing in women," said lead author Yasamin Sharifzadeh, a medical student at Virginia Commonwealth University.

It was Sharifzadeh who first sought to study the relationship between pain catastrophizing and opioid prescriptions as a third-year undergraduate student at Stanford, where the research was conducted. She says more research is needed to understand sex differences in pain so clinicians can develop better treatments for both men and women.

“If physicians are aware of these gender-specific differences, they can tailor their treatment,” she said. “When treating chronic pain patients — especially women — they should analyze pain in its psychological aspect as well as its physical aspect.”

Previous studies have found that women are more likely to have chronic pain, be prescribed prescription pain relievers, be given higher doses, and to use them for longer periods. Women may also become dependent on medication more quickly than men, according to the CDC.

Chronic Pain Raises Risk of Dementia

By Pat Anson, Editor

Chronic pain has long been associated with a variety of health problems, including depression, anxiety, insomnia, high blood pressure and an impaired immune system. Now there’s something else to worry about.

A large new study by researchers at UC San Francisco has found that older people with chronic pain experience faster declines in memory and are more likely to develop dementia, an indication that chronic pain could cause changes in the brain. The study, published in JAMA Internal Medicine, appears to be the first to make this association.

UCSF researchers analyzed data from over 10,000 participants aged 60 and over who were enrolled an ongoing national study of older Americans. Patients were surveyed about their pain and cognition in 1998 and 2000.

Those who said they were persistently troubled by moderate or severe pain declined 9.2 percent faster in tests of their memory and cognitive ability over the next 10 years than those who said they were not troubled by pain.

The patients who complained about persistent pain also had a 7.7 percent greater chance of developing dementia.

“A persistent report of moderate to severe pain, which may reflect chronic pain, is associated with accelerated cognitive decline and increased dementia probability in a large population-representative data set of elders,” wrote first author Elizabeth Whitlock, MD, a postdoctoral fellow in the UCSF Department of Anesthesia and Perioperative Care.

“Clinicians should be aware of this association, which persisted after extensive statistical adjustment for confounding health and demographic factors. Patients reporting ongoing pain may be at higher risk for current and incident cognitive impairment and physical debility.”

Whitlock says the additional loss of memory in participants who reported persistent pain suggests that they will have a harder time with daily living tasks, such as managing their medications and finances.

"Elderly people need to maintain their cognition to stay independent," she said. "Up to one in three older people suffer from chronic pain, so understanding the relationship between pain and cognitive decline is an important first step toward finding ways to help this population."

The data that the researchers analyzed did not include information about opioid use, so researchers could not tell which of their participants were taking opioid painkillers. While opioid use could be the cause of the cognitive changes, so could the pain itself. For example, a recent study of chronic pain sufferers found that those who took non-steroidal anti-inflammatory drugs (NSAIDs) had nearly the same increased dementia risk as those taking opioids.

"This means we have to consider the potential direct effects of chronic pain on cognition," Whitlock said.

People who suffer from chronic pain tend to have diminished attention and impaired memory, and Whitlock says when pain is severe it could divert enough attention to interfere with the consolidation of memory. Another possibility is that the emotional stress of being in pain activates stress-hormone pathways in the body that have been implicated in cognitive decline. If either is the case, she said, then effectively treating the pain could protect cognition.

"This is something I really feel we can do something about as clinicians," Whitlock said. "It's part of taking care of the whole patient."

How Chronic Pain Changes Nerve Signals

By Pat Anson, Editor

Swedish researchers have developed a surprising new theory about what causes chronic nerve pain and why it is so difficult to treat.  

It has long been assumed that some sensory neurons only transmit pleasant tactile sensations, while others specialize in transmitting pain. But scientists at Karolinska Institutet have discovered that neurons that normally allow us to feel a caress or soft touch can switch roles and start signaling pain after nerve damage.

The researchers identified a small RNA molecule (microRNA) in neuron cells that regulates how touch is perceived. Levels of the molecule drop after neurons are damaged, which raises levels of a specific ion channel that makes the nerves sensitive to pain.

"Our study shows that touch-sensitive nerves switch function and start producing pain, which can explain how hypersensitivity arises," says Professor Patrik Ernfors at Karolinska Institutet's Department of Medical Biochemistry and Biophysics.

"What's interesting about our study is that we can show that the RNA molecule controls the regulation of 80 per cent of the genes that are known to be involved in nerve pain. My hope, therefore, is that microRNA-based drugs will one day be a possibility."

The research was primarily conducted on mice but also verified in tests on human tissue, where low microRNA levels could be linked to high levels of the ion channel and vice versa, suggesting that the mechanism is the same in humans. Researchers believe the study findings, published in the journal Science, could lead to more effective pain treatments   

"It's vital that we understand the mechanisms that lead to chronic nerve pain so that we can discover new methods of treatment," says Ernfors. "The pharmaceutical companies have concentrated heavily on substances that target ion channels and receptors in pain neurons, but our results show that they might have been focusing on the wrong type of neuron."

Neuropathy and chronic nerve pain are common conditions, but the drugs available to treat them have limited efficacy. One widely used medication that blocks ion channels -- gabapentin (Neurontin) – is only effective in about half of the patients who take it, according to Ernfors.

Research Uncovers Why Some Pain Meds Don’t Work

By Pat Anson, Editor

An international team of researchers may have discovered why some pain medications are inneffective: they target receptors on the surface of nerve cells that have moved out of reach.

Their findings, published in the journal Science Translational Medicine, may lead to the development of a new class of pain medication that is more potent and less prone to side effects than opioids and non-steroidal anti-inflammatory drugs (NSAIDs).

"Opioids and NSAIDs do not work for everyone and have unacceptable side effects, particularly when used over a long period of time," said Nigel Bunnett, PhD, a professor of surgery and pharmacology at Columbia University Medical Center.

"However, previous efforts to develop more effective analgesics have been stalled by our limited understanding of the mechanisms that allow nerves to sense and transmit pain signals."

Many pain medications work by targeting protein receptors on the surface of nerve cells that transmit pain signals. One receptor – known as the neurokinin 1 receptor (NK1R) -- causes pain and inflammation when activated.

In a series of laboratory experiments on rodents, Bunnett and his colleagues discovered that NK1R, when stimulated by pain, quickly moves from the cell surface to inside the cell membrane, where it continues to function outside the reach of pain medication. Researchers found that when they added a lipid (fat molecule) to painkillers that can cross the cell membrane, they effectively blocked NK1R and provided potent and durable pain relief to the rodents.

"From these experiments, we have demonstrated that designing NK1R inhibitors that are capable of reaching the endosomal network within nerve cells may provide much longer-lasting pain relief than currently available analgesics," said Bunnett. "We think that modification of many existing compounds, as we did with NK1R inhibitors, may have the potential to enhance the effectiveness of many different classes of medications."

The next step for researchers is to see if the same results can be found in humans. If proven, it could mean that current pain medications could be redesigned to make them more effective.

"This is a proof-of-concept study that shows that we can re-engineer current pain drugs and make them more effective. The challenge is now to translate the technology into human clinical trials. This is a complex and challenging path – but the ultimate benefits to patients with nerve pain are potentially highly significant," said Dr. Meritxell Canals of Monash Institute of Pharmaceutical Sciences at Monash University in Australia.

The study was supported by grants from Australia’s National Health and Medical Research Council, the Australian Research Council, and Takeda Pharmaceuticals.

Study Finds ‘Nocebo Effect’ of Statins Cause Pain

By Pat Anson, Editor

An industry funded study is adding more fuel to a sometimes heated debate over statins – and whether the cholesterol-lowering drugs cause muscle pain and weakness.

Research involving nearly 10,000 patients published in The Lancet medical journal suggests that people taking Lipitor – the brand name for the statin atorvastatin -- are more likely to report muscle aches and other side effects, but only if they knew there were taking the drug.

This is what is called the “nocebo effect” – the opposite of the placebo effect – where people complain of side effects because they expect to have them.

"Just as the placebo effect can be very strong, so too can the nocebo effect. This is not a case of people making up symptoms, or that the symptoms are 'all in their heads'. Patients can experience very real pain as a result of the nocebo effect and the expectation that drugs will cause harm,” said lead author Peter Sever of the National Heart and Lung Institute at Imperial College London.

“What our study shows is that it's precisely the expectation of harm that is likely causing the increase in muscle pain and weakness, rather than the drugs themselves causing them."

Sever said complaints about the side effects overstate how common the problems are and discourage people from taking statins, resulting in "thousands of fatal and disabling heart attacks and strokes, which would otherwise have been avoided."

“These results will help assure both physicians and patients that most AEs (adverse effects) associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects,” he said.

The study was funded by Servier Research Group, Leo Laboratories and Pfizer – the maker of Lipitor. Five of the eight co-authors reported potential conflicts of interest, including payments from Pfizer and other drug makers that manufacture statins.  

Only about 2 percent of the patients taking Lipitor in The Lancet study reported having muscle pain, a finding that is substantially at odds with previous research.

For example, in a study at the Cleveland Clinic last year, 42 percent of patients taking Lipitor reported muscle pain and weakness. Other studies have found muscle pain in 5% to 29% of statin users.

The Food and Drug Administration considered the problem serious enough that in 2014 it required warning labels on statins, cautioning that some statins can cause a muscle injury called myopathy, which is characterized by muscle pain or weakness. In rare instances, the FDA says statins can also cause liver injury, diabetes and memory loss.

Another study this week, published in JAMA Internal Medicine, linked statin use to back pain conditions such as spondylosis and intervertebral disc disorders. The study involved over 13,000 military veterans and their families.

“To our knowledge, this study is the first to report greater odds of back disorders among statin users compared with the odds of nonusers in a population with equal access to and the same cost of health care,” said Una Makris, MD,  of the VA North Texas Health Care System in Dallas. “Our results provide additional motivation to further investigate the overall influence of statin therapy on musculoskeletal health, specifically if prescribed for primary prevention in physically active individuals.”

Study Finds Alcohol Risky but Effective Pain Reliever

By Pat Anson, Editor

The dangers of alcohol are well known – from drunk driving to health, work and social problems. But with opioid painkillers becoming harder to obtain, some chronic pain sufferers are turning to alcohol to dull their pain.

And now there’s research to back them up.

In an analysis of 18 studies published in the Journal of Pain, British researchers found “robust evidence” that a few drinks can be an effective pain reliever.

“Findings suggest that alcohol is an effective analgesic that delivers clinically-relevant reductions in ratings of pain intensity, which could explain alcohol misuse in those with persistent pain despite its potential consequences for long-term health,” wrote lead author Trevor Thompson, PhD, University of Greenwich.

Thompson and his colleagues say a blood-alcohol content of .08% -- which meets the legal definition of drunk driving in many U.S. states – produces a “moderate to large reduction in pain intensity” and a small elevation in pain threshold.

“It can be compared to opioid drugs such as codeine and the effect is more powerful than paracetamol (acetaminophen),” Thompson told The Sun newspaper.  “If we can make a drug without the harmful side effects then we could have something that is potentially better than what is out there at the moment.”

Despite the risks involved, some pain sufferers are turning to alcohol as a last resort and mixing it with pain relievers – a potentially lethal combination.

“My doctor took me off all opioids last year and put me on Effexor, Naproxen, and extended relief Tylenol. It barely touches my pain so I am also drinking each night to help dull the pain,” one patient told us.

“The doctor tried gabapentin but I ended up with an overnight stay in the hospital due to a bad reaction to the medication,” another patient said. “I'm now using alcohol nightly to help me sleep along with high amounts of Naproxen and Tylenol daily.”

“I suffer extreme back and neck pain. Since they no longer prescribed painkillers I started drinking and find it is helpful. I take also thousand mg of arthritis Tylenol every day,” wrote another patient.  “It's either suicide or drinking. Frankly I'd prefer death. Too bad they can't give painkillers anymore.”

How much is too much?

According to the Mayo Clinic, moderate alcohol consumption for healthy adults means up to one drink a day for women of all ages and men older than age 65, and up to two drinks a day for men age 65 and younger.

The Media’s Addiction to Opioids

By Roger Chriss, Columnist

A recent and very brief CDC report described 59 pneumonia deaths in Minnesota between 2006 and 2015 that involved opioids. The gist of the study was that “opioid users are at increased risk for pneumonia” and therefore the deaths should have been reported as opioid related overdoses, even though the autopsy reports list pneumonia as the cause of death.

Vox said the study suggests “the opioid epidemic may be even deadlier than we think,” while the Daily Mail warned it was “just the tip of the iceberg” and that “we may have grossly underestimated the scale of the opioid epidemic.”

JAMA Surgery also recently published a study, which found that about 6 percent of surgery patients continued to use opioids more than three months after their surgery.

U.S. News cited the study to proclaim that “Many Opioid Addictions Surface After Surgery,” while MedicalXpress said it was proof that someone could go “from opioid-free to long-term user, in one operation.”

Both the CDC report and the JAMA Surgery study were grossly misrepresented. Fear sells, and the opioid crisis has become a favorite source of fear-mongering in the media.

The CDC report is a one page, four-paragraph document released by the agency’s Epidemic intelligence Service (EIS). It never mentions the words “addiction” or “epidemic,” yet it leaps to one very big conclusion.

“The total burden of opioid-associated deaths was underestimated in Minnesota,” the report says. “The contributions of opioid toxicity, infectious disease, or their interactions to death are challenging to disentangle; understanding these interactions might inform future opioid-related mortality prevention efforts.”

The JAMA Surgery article is a retrospective study which found an association between post-operative use of opioid medications for pain management and patient history of smoking and alcohol use. The study looked at opioid abuse only as an exclusion criteria for the patient population; it was not a study about addiction in any form. The JAMA article concludes by saying that “new persistent opioid use represents a common but previously underappreciated surgical complication that warrants increased awareness.”

In other words, we have intriguing results that should be investigated further, with the ultimate goal of improving public health and welfare. Unfortunately, all that is lost in the alarmist media coverage that mischaracterizes the findings, over-interprets the data, and extrapolates consequences to reach what at best are highly premature conclusions.

In its coverage of the CDC report, CNN quoted EIS officer Victoria Hall, DVM, as saying that the Minnesota data represents “an iceberg of an epidemic.” 

Keep in mind that Hall is not an epidemiologist, an infectious disease specialist or an expert on icebergs. She is a veterinarian by training and a recent graduate of Mississippi State University's College of Veterinary Medicine. Hall has been working for the CDC less than a year, according to her LinkedIn profile.

In a CDC media briefing, Hall refers to only one specific case in Minnesota: a middle-aged man dying of pneumonia, who was on opioid therapy for chronic back pain. This case is not mentioned in the CDC EIS report. His death may be an important hint of a new facet of the opioid crisis, or it may be an anomalous outcome. More work is needed to figure out what is really going on. For now, it bears remembering that the plural of anecdote is not data.

VICTORIA HALL, DVM

Similarly, U.S. News reported on the JAMA Surgery article by stating that, “Some surgery patients prescribed opioids for post-operative pain relief may face a high risk for developing a long-term opioid addiction, new research warns.” This report also appeared on Philly.com  and on WebMD , spreading the misinformation about addiction risks, which were never even mentioned in the article.

In other words, there was a huge and speculative leap from the data in the CDC report about 59 opioid-related pneumonia deaths over a decade-long period all the way to a stealth epidemic sweeping the nation. And an equally large jump from an association between the duration of post-surgical opioid use and patient social history to a new source of opioid addiction.

The sensible response is to call for further research. For the CDC, this means collecting data from all 50 states about otherwise unexplained deaths and seeing if opioids are involved in any of them, then following up with analysis on possible under-reporting. For the world of surgery, this means performing prospective trials to see if the reported association holds up, and then investigating if such use increases the odds of a patient developing opioid use disorder.

For now, we just don’t have the data to figure out what is going on. And as Sherlock Holmes says: “It is a capital mistake to theorize before one has data.”

Roger Chriss suffers from 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.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.