Ideology Is Guiding Pain Care, Not Science

By Roger Chriss, PNN Columnist

An overarching question in pain management and the opioid crisis is whether or not prescription opioids have any value in treating chronic non-cancer pain. 

Some say that the answer is a resounding “No.” Studies to date on the effectiveness of opioids are often too small, methodologically weak or too short-term to be convincing. But these same studies are often used to claim lack of efficacy, and for the same reasons they cannot do that.

At present, we don’t know if or how well opioids work for chronic pain. To establish efficacy, we’d need major studies or clinical trials that run for years, using many hundreds or even thousands of patients. Opioids would need to be compared to placebo or other treatments for various forms of chronic non-cancer pain, from inflammatory and autoimmune conditions to neuropathies and genetic disorders.

Such studies have not been done. A U.S. government website that tracks clinical studies lists 685 trials for “opioids and chronic pain,” with several terminated or withdrawn, others just now recruiting, and only a handful completed. Many of these studies look at substance use disorders, tapering or de-prescribing, or are small-scale efforts at comparing two opioids.

There are no large-scale studies of opioids for chronic non-cancer pain getting started or underway at present.

There are over 14,500 studies on “opioids and chronic pain” listed in PubMed, a database maintained by the National Institutes of Health. One of the few that looked at long-term use of opioids is the 2018 SPACE study, which found that opioids were not superior to non-opioid medications over 12 months.

But the SPACE study has important limitations: It only looked at patients with chronic back pain or osteoarthritis of the hip and knee. Researchers also put the opioid tramadol in the non-opioid group and let some patients switch from the non-opioid to the opioid arm in order to achieve good analgesia.

Another study found that only one in five patients benefited from long-term opioid therapy, with young and middle-aged women showing the least improvement in pain and function. But this was a telephone survey that relied on a pain scale to assess outcomes, with no mention of diagnoses and no randomization or placebo control.

Similar studies with more positive outcomes can be found. According to a Cochrane review, the opioid tapentadol (Nucynta) worked better than oxycodone and a placebo in treating chronic musculoskeletal pain. But the clinical significance of this finding is uncertain.

In other words, we don’t have the kinds of studies we need to figure out if opioids work for chronic pain. This means that when people claim there is no good evidence for opioids in long-term pain management, they have a point. But for the same reason, there is no good evidence against opioid efficacy, either.

Of course, there is good evidence about opioid risks. As PNN reported, an Australian study found that people on long-term opioids do sometimes engage in risky behavior such as filling a prescription early. But this study didn’t find major risks of dose escalation, diversion or overdose that are often claimed to be common.

The solution would be to do major trials. But there seems to be little incentive to do this. The opioid crisis and associated ideological debate about drug legalization have combined with lawsuits and public health policy to remove any motivation to find out more about efficacy. The results of such a study could sway outcomes in the ongoing opioid litigation or ignite new lawsuits, or could even cripple advocacy groups on either side of the opioid divide.

There are, arguably, subtle incentives not to pursue high-quality clinical trials on opioids for long-term pain management. Instead, we’re seeing lots of meta-analyses, reviews, and retrospective studies, none of which is particularly convincing because summarizing old studies with known weaknesses generally cannot answer big questions.

For the foreseeable future, we may be stuck with ideology instead of science guiding clinical pain care.

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. 

Medical Cannabis Needs Better Research

By Roger Chriss, PNN Columnist

Much of the uncertainty and reluctance about using medical cannabis stems from a lack of high-quality research. Instead of randomized controlled trials, surveys and data-mining are commonly seen, leaving clinicians and policymakers with little to work with.

That is the basis for the American Medical Association’s concerns about states legalizing medical cannabis.

“Scientifically valid and well-controlled clinical trials conducted under federal investigational new drug applications are necessary to assess the safety and effectiveness of all new drugs, including potential cannabis products for medical use,” the AMA declared in a policy statement.

Good research would help reduce such concerns. Unfortunately, a lot of recent research involves poor methodology and problematic funding, weakening potentially useful results.

For example, a recent study published in the journal Cureus found that cannabis was a “useful adjunct and substitute for prescription opioids” for chronic pain patients and had the added benefit of improving their physical function and quality of life.

To conduct the study, researchers surveyed 550 patients being treated at three licensed medical cannabis clinics in the northeastern United States, using an anonymous online survey consisting of 11 questions about medication use, pain levels and side effects.

This is very problematic. A convenience sample is a simple method for quickly grabbing data. Its downsides are that it isn't random and is subject to a lot of selection bias. And anonymous surveys are unreliable. As a 2018 Australian study showed, claims of prescription opioid use by people using medical cannabis are often very inaccurate.

Similarly, an observational study at 21 medical clinics in Canada found that the “high rate of cannabis use for chronic pain and the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis.”

But the study was sponsored by Tilray, a Canadian cannabis firm that has provided cannabis for clinical trials and is involved in the adult recreational-use market in Canada. Drug studies sponsored by industry need to be viewed with caution, since such studies are known to produce results favorable to the sponsoring organization.

In general, studies that collect data through convenience samples or anonymously via online surveys or apps are not reliable. And studies funded by industry may be biased.

What Happened to Sue Sisley’s Study?

Good studies do get done. However, their results are not always published.

In 2019 Sue Sisley, a psychiatrist at the Scottsdale Research Institute in Phoenix, finished a study on cannabis for post-traumatic stress disorder (PTSD) that took ten years to complete, promising that “the full results of the study, including all the data, will be publicly released."

But Sisley’s research still hasn’t been published. Last year she admitted the study findings may have been compromised by the poor quality of cannabis that the DEA allows for research.

“Most scientists end up with this mishmash of different strains (including stem sticks, leaves, etc.) — all of it seems to get thrown into a grinder in an overzealous effort to standardize the study drug batches for clinical trials," Sisley said.

Research results need to be published even if they are not positive. There is a tendency to promote positive results and hide negative findings. Publication takes a lot of time and effort, and negative results may impede the flow of research dollars.

But if the benefits and risks of medical cannabis are to be better understood, we need all the results. And researchers should get full credit for their work, even if the results aren’t what advocates or enthusiasts were hoping for.

Medical cannabis needs more high-quality research. Surveys of people recruited from a medical cannabis dispensary cannot be generalized to the population at large, and studies sponsored by industry must be treated with caution. Improving medical cannabis research will go a long way toward helping people use medical cannabis safely and effectively.

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.

Sex Bias Persists in Pain Research

By Pat Anson, PNN Editor

It’s long been known that women are more likely than men to have chronic pain conditions such as fibromyalgia, rheumatoid arthritis, irritable bowel syndrome (IBS) and migraine. Women are also more likely to feel more severe, recurring and longer lasting pain.

Why then are women less likely to receive pain treatment? And why are some treatments less effective for women?

One obvious reason is that men and women have different biology and process pain differently. Another is a “blind spot” in pain research, which is more focused on studying males than females, according to a new review published in the journal Nature Reviews Neuroscience.

"The pain literature is biased such that, because of the overwhelming use of male animals in experiments, we are increasingly learning about the biology of pain in males. And wrongly concluding that this is the biology of pain. It's only the biology of pain in males," says author Jeffrey Mogil, PhD, a Professor of Psychology and Anesthesia at McGill University in Montreal.

Mogil reviewed over 1,000 research articles published in the journal Pain between 2015 and 2019, and found a distinct change in the sex of laboratory animals used in research. In 2015, for example, 80 percent of the studies only used male rodents. By 2019, half of studies were male-only.

SOURCE: Nature Reviews Neuroscience.

The trend towards using both male and female animals may sound like a promising change in research design. But when Mogil looked more closely at sex differences in pain literature, he found clear evidence that a male bias still exists in pain research.

"The very ideas we come up with for experiments, are based on experiments in males and therefore they work in males and not in females,” says Mogil.

Even in studies that included both male and female rodents, Mogil found that the research was often geared toward the males’ response. In experiments that “worked out” -- meaning the scientific hypothesis being tested was found to be true -- over 72% of the male rodents had a positive response, while only about 28% of the female rodents did. That strongly suggests the research was biased even before the experiments began.

"If there were no bias in the literature and there were a number of papers where the experiment worked in one sex and not the other, it should work in females just as often as in males,” explained Mogil. “Why has this happened? Because the hypothesis that that experiment tested out was generated based on prior data from experiments on only males. So, of course, it only worked in males."

The bias in research can have lasting effects on pain treatment and may help explain why some analgesic medications are more effective when taken by men.

"This research suggests that lots of what's in the pipeline right now, if it works in anyone at all, will largely be men. Whereas the clear majority of chronic pain patients have been and continue to be women," Mogil said.

Steps have been taken to reduce bias in pain research. If they want to get government funding, researchers in the United States, Canada and several European countries are now required to evaluate both sexes in their research. Mogil is optimistic those policies will eventually make a difference, but it may take awhile to undo decades of research that focused primarily on male animals.

“Performing biomedical experiments in both sexes is not only the ethically correct thing to do but also the scientifically correct thing to do, especially if we wish to reverse the particularly unimpressive track record of clinical trial success in the past few decades,” Mogil wrote.

Fibromyalgia Researchers, It’s Time to Stop Watching the Flowers Grow!

By Donna Gregory Burch

As a fibromyalgia warrior and blogger, I read a lot of articles about new research findings. I continue to be amazed by how much time and money are wasted by researching the obvious or studying the same treatments over and over again.

After all, how many times do we need to prove meditation can reduce fibromyalgia pain? Didn’t we figure that out years ago?

I really thought I’d seen it all until an article entitled, “The Power of Flowers May Ease Fibromyalgia Symptoms,” showed up in my inbox last month.

As I read it, I literally said out loud: “Are you kidding me?”

In case you haven’t read the article, it summarizes a recent Israeli study in which 61 women with fibromyalgia completed a 12-week flower design course presented by a trained florist. At the end of the course, Tel-Aviv University researchers reported “quite amazing” improvements in the women’s fibromyalgia symptoms.

Yep, you read that right: The researchers claim arranging a few daisies and baby’s breath in a vase actually improves fibromyalgia.

Now, I don’t doubt for a minute that flower arranging is relaxing and could have a calming effect on the central nervous system. That, in turn, could lead to a reduction in pain and other fibro symptoms.

But so could watching butterflies or painting rocks.

While I think it’s wonderful researchers are looking at non-pharmaceutical treatments for fibromyalgia, studies like this completely invalidate the seriousness of our condition. These types of studies make it seem like almost anything will fix fibro, and that is just not reality.

Because of the stigma of fibromyalgia, we already struggle to prove to our doctors and loved ones that we’re really sick. What do you think the average person is going to think when they read flower arranging helps fibromyalgia? While I’m sure the researchers had good intentions, this study makes a complete mockery and joke out of an extremely painful, life-sucking condition.

In my mind, I think back to all of those doctors who tried to give me anti-depressants and anti-anxiety medications when I complained about unexplained pain, fatigue, bladder urgency, neuropathy and a long list of other symptoms. The message was clear: “It’s all in your head. You’re just a stressed out, middle-aged woman who needs to chill out.”

What happens when these same doctors read the Israeli study? I can envision them now referring their patients to the nearest community college for classes on cupcake baking and basket-weaving. As if we weren’t frustrated enough with the conventional medical system!

The truth is we don’t need more BS fibromyalgia studies like this one. We need researchers to get serious! We need them to take a deep dive into the minds and bodies of fibromyalgia patients and figure out what causes us to feel like a three-day-old warmed over microwave dinner.

We need real solutions – treatments that get to the root cause of our illness – not a new hobby!

Donna Gregory Burch lives with fibromyalgia and chronic Lyme disease. Donna covers news, treatments, research and practical tips for living with fibromyalgia and Lyme on her blog, FedUpwithFatigue.com. You can also find her on Facebook and Twitter.

Donna is an award-winning journalist whose work has appeared online and in newspapers and magazines throughout Virginia, Delaware and Pennsylvania. She lives in Delaware with her husband and their many fur babies.

Is Your Pain Medication Effective or Was It Placebo Effect?

By Dr. Lynn Webster, PNN Columnist

Most of us have been prescribed a medicine at some time in our lives. And if we got better, we probably assumed it was because the medication was effective.

However, this may not have been completely true. A positive result following the use of a medication may have little to do with the drug.

If you're a M*A*S*H fan, you may have seen an episode called "Major Topper." In that show, Colonel Potter suggests they treat people in pain with a placebo because there is a morphine shortage — and it works. Did that mean their pain wasn’t real?

Placebos Work So Well They Can Fool Researchers

One of the greatest challenges in evaluating the efficacy of medical treatments is to minimize what is known as the placebo effect. The benefit provided by a treatment during clinical trials may appear to be significant. However, the treatment may fail to be approved by the FDA if the benefits for patients who receive a placebo are too similar to those who receive active treatment.

Drug approval requires that active treatment results are meaningful and differ statistically from placebo results, even though both may provide similar outcomes when compared to a baseline. 

I study drugs for their potential to be abused— what the FDA calls a Human Abuse Potential (HAP) study. People who participate in HAP studies must admit they recreationally use the class of drug which is undergoing evaluation, and must report a strong preference for the drug when compared to a placebo.

Most people would be surprised to learn that as many as 50% of the test subjects who commonly use a drug recreationally cannot adequately differentiate between the active drug and the placebo. Even more surprising is that one in five subjects report a much greater preference or “getting high" experience with the placebo than with the active drug.

There are several reasons for this. It could be that they don’t realize researchers know which drug they received and in what order. They are simply hoping to guess correctly because they want to participate in the study. Or the subjects may be anticipating an effect that they want (to get high) and that anticipation creates the effect in the reward center of their brain without even using an active drug.

This effect is not limited to drugs. As a principal investigator in a study, I surgically implanted wires at the base of the occiput (the skull) to stimulate occipital nerves in an attempt to prevent or treat migraine headaches. Although all subjects underwent the operation and were implanted with the wires, only half received active stimulation. The other half were programmed with a sham pattern of stimulation.

When the study was unblinded, we discovered that almost everyone in both groups (active and placebo) derived remarkable, but similar, relief from the therapy.

We concluded it was their expectation that an invasive procedure would be therapeutic that provided the positive outcome. Unfortunately, the positive results of both treatment and placebo meant the new procedure could not be approved on the basis of our testing.

Placebos Work Even When People Know About Them

Ted Kaptchuk, a Harvard Medical School professor of medicine, is the director of the Program in Placebo Studies at the Beth Israel Deaconess Medical Center. In a recent episode of NPR's "Hidden Brain" podcast, Kaptchuk recounts similar results when testing the placebo effect.

However, his research added a new twist. Kaptchuk wanted to see what would happen if he used "radical honesty" to determine the potential of the placebo effect. Instead of tricking patients into believing they may receive an actual treatment instead of a placebo, Kaptchuk told his subjects they would receive a placebo. In other words, no actual drug would be administered to subjects and they were all aware of that.

Surprisingly, he found that a placebo could still work. "Hidden Brain" host Shankar Vedantam also talked to Linda Bonanno, who participated in Kaptchuk's study. Bonanno explained that Kaptchuk gave her a placebo to treat her irritable bowel syndrome and it eased the agonizing pain she had been living with for years.

The pain did not return until Kaptchuk stopped "prescribing" the placebo. For Bonanno, what seemed to help the most was the trusting relationship she had with Kaptchuk. The warmth and caring of her health care provider may have been enough to mitigate her pain.

As we know, pain isn't just a physical experience. It is a complex emotional experience that has psychological, social and spiritual elements. If a doctor's empathy, warmth, listening and caring can ease a patient's pain, that shouldn’t call into question whether the patient's pain was real. It simply makes the case that a trusting relationship with a healthcare provider is as important for successful treatment as the medication or procedure itself.  

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

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.

Government Grown Cannabis May Be Harming Research

By Roger Chriss, PNN Columnist

Physician researcher Sue Sisley, MD, has filed suit against the federal government over the quality of cannabis provided for her study on post-traumatic stress disorder. Sisley claims that the cannabis supplied by the DEA-sanctioned facility at the University of Mississippi is “suboptimal.”

Sisley told Green Entrepreneur that the DEA provided "standardized green powder that is just cannabis ground up.” She also said that the plants were moldy and contained sticks and seeds. 

Sisley is not the first researcher to say government cannabis intended for research is not the same as the cannabis available in dispensaries. This of course poses a key question: What is research cannabis?

Cannabis is a plant. Specifically, cannabis is the genus of a plant that includes the species C. sativa, C. indica, and C. ruderalis. There is still dispute if C. ruderalis should be included with C. sativa, or if all three species should be considered a single species, C. sativa. 

There is no precise pharmacological definition of medical cannabis. There is no agreed-upon level of THC, CBD, or other cannabinoids, and no accepted terpene profile. In dispensaries, cannabis comes in a large variety of strains used in a wide range of products. 

There is poor consistency among strains. Leafly recently attempted to measure the reliability of cannabis strains and found that even the most reliable ones were far from consistent at the levels necessary for clinical research.

Moreover, cannabis is a moving target. Because it is a commercial product often intended for nonmedical use, it is subject to a variety of market forces involving its various psychogenic effects. And new strains are introduced regularly. 

Further, cannabis products are consumed in many different ways, such as smoking, vaporizing, ingesting and through the skin . The bioavailability of cannabis varies significantly by route of consumption because of different absorption levels and metabolism. So whatever research cannabis is used would have to be specified by strain, amount and route of administration. 

For research purposes, that requires precise information. But as Genetic Engineering & Biotechnology News reported, medical cannabis comes in so many forms and has so many different uses that it presents a "unique challenge to cannabis testing laboratories." No existing test provides a good model on how to proceed.

In other words, there is no clear definition of research cannabis and there is no practical way to reliably test commercial strains with a consistency adequate for clinical studies. 

This means the definition of research cannabis is arbitrary. Researchers and advocates keep adjusting the definition or questioning the quality to explain away poor outcomes. According to Microscopes and Machines, when Dr. Sisley's PTSD study concluded, she unblinded the data and quickly came to realize the quality of cannabis provided by the University of Mississippi "had negatively affected the study’s efficacy data.”

But we cannot define research cannabis as the form of cannabis that only gives the results we were hoping for. This would be circular and self-justifying. It would also be self-defeating since we’d never know what, if anything, cannabis has to offer. 

Cannabis is a plant, not a laboratory-synthesized chemical being turned into a USP-grade pharmaceutical. As Jonathan Stea wrote in Scientific American,“it is best to conceptualize cannabis as a chemical soup with over 500 ingredients that can be served in countless different ways.”

This means that researchers will need to define their cannabis before starting a study. And the U.S. government will need to provide such cannabis. Fortunately, the National Institutes of Health is responding by producing more varieties of cannabis.

A more favorable legal landscape would also help. There may not be any “research cannabis” per se, but cannabis is certainly worth researching. 

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.

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.

Insufficient Evidence: How Opioid Deniers Spin Studies

By Roger Chriss, Columnist

Opioid medications are coming under fire again as being ineffective for chronic pain management.

Charles Pattavina, MD, president of the Maine Medical Association, told the Portland Press Herald that "there is no clinical indication for opioid medication for the treatment of chronic pain."

And Stanford psychiatrist Anna Lembke, MD, said in Vox that “if opioids worked long-term, I would have no problem with patients taking them.”

But sweeping generalizations like these oversimplify a complex situation. Chronic pain is a highly heterogeneous feature of a wide variety of diseases and disorders. And opioids are a broad class of pain medications that come in different doses and are administered by different routes.

Thus, a claim that opioids do not work for chronic pain is too simplistic. Medical researchers investigate carefully posed questions about specific drugs and conditions using the statistical method known as hypothesis testing.

Researchers cannot and do not investigate if “opioids” work for “chronic pain.” Good research is more narrowly focused, such as these clinical studies:

“Tapentadol extended release for the management of chronic neck pain”

“Effectiveness and Safety of Once-Daily Extended-Release Hydrocodone in Individuals Previously Receiving Immediate-Release Oxycodone for Chronic Pain”

“Oxycodone for neuropathic pain in adults”

The results are equally specific. In the first example above, the authors conclude that “our results suggest that tapentadol ER, started at 100 mg/day, is effective and well tolerated in patients with moderate-to-severe chronic neck pain, including opioid-naïve subjects.” Similarly precise statements are found in any such article.

Sometimes researchers will perform a meta-analysis or review in which they assemble a collection of existing research articles and, after a statistical analysis, attempt to draw broader conclusions. Examples include:

“Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects”

“Opioids for chronic pain: new evidence, new strategies, safe prescribing”

“The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop”

The last article above is often cited by opioid deniers, even though it concludes that “evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function.”

"Evidence is insufficient” means that no determination can be made one way or the other about opioid medications. It does not prove that opioids are ineffective for chronic pain.

This leads to the final defense of opioid deniers: Demand an impossibly high standard of evidence. Specifically, they want the “gold standard” of clinical research: a double-blind, placebo-controlled, randomized trial of a specific drug for a particular condition.

To satisfy this standard, we would have to test every opioid medication against every medical condition causing chronic pain in a variety of different groups of people. This would mean thousands of trials, each performed multiple times, before any meaningful conclusions could be drawn about opioid medications in general. The time and costs involved would be prohibitive in the extreme.

So instead we use observational data and statistical methods to derive reasonable conclusions, as found in the articles above. This approach is widely used in many areas of medical research. In pain research, it has clarified how certain opioid medications can be used to address various chronic pain conditions.

To be clear, opioid therapy can help manage a variety of forms of chronic pain. Not all pain, and not for all patients. And always under the care and guidance of medical professionals.

The goal of opioid therapy is to improve quality of life, and available evidence strongly supports that it does so.

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.

Trump Budget Cuts Would Further Limit Pain Research

By Pat Anson, Editor

The Trump administration has proposed another $1.2 billion in budget cuts for the National Institutes of Health (NIH), which experts say could hamper already anemic efforts at developing new treatments for chronic pain.  Most of the reductions at NIH would come from research grant funding.

Only about 1 percent of the NIH budget is designated for pain research, even though more Americans suffer from pain than heart disease, diabetes and cancer combined.

The proposed $1.2 billion reduction in this year’s NIH budget is in addition to the $5.8 billion cut the Trump Administration has already proposed for the agency in 2018.

The $7 billion in savings will be used to help pay for an enhanced border wall with Mexico and increased military spending.

The White House Office of Management and Budget says the NIH budget for 2018 “eliminates programs that are duplicative or have limited impact on public health” and would “help focus resources on the highest priority research and training activities.”

"I will be the first one down lobbying against this," said Ann Romney, who suffers from multiple sclerosis and is the wife of former GOP presidential nominee Mitt Romney.

"Nothing comes from nothing. If you don't have that funding, there will be nothing," she told Yahoo News. "There will be no new treatments, there will be no new drug therapies. Progress in medicine will come to a halt."

Pain Research Already Limited

The lack of spending on pain research -- by both the government and the healthcare industry – was a problem long before the Trump administration came out with its budget plans.

In 2012, researchers at Johns Hopkins University estimated that chronic pain costs the U.S. economy up to $635 billion a year in healthcare costs and lost productivity. Yet the NIH spent only $358 million on pain research that year, according to journalist Judy Foreman in her book, “A Nation in Pain.”

“It is a huge burden with very little actual research going into it. And still a lot of unmet medical need,” said Gabriel Baertschi, CEO of Grünenthal, a German pharmaceutical company. “The odds of succeeding in pain research are lower than in other areas. It’s much more complex than other diseases in a sense that if you hit one target you are not necessarily resolving pain. Pain is multi-dimensional. That explains why from a research point of view you don’t always succeed.”

Grünenthal is a research-oriented company that focuses on finding new treatments for conditions such as bladder pain and Complex Regional Pain Syndrome (CRPS). Recently the FDA designated an experimental drug being developed by Grünenthal as a potential breakthrough therapy for CRPS. The company is now in advanced stages of clinical trials.

Because it’s smaller and privately owned, Baertschi says Grünenthal can afford to explore new treatments for rare diseases that “Big Pharma” companies are not interested in developing.

“Most of the companies that were active in pain have closed their pain research centers,” he told PNN in an interview last month. “I think a lot of companies are pulling out because the cost of developing pain drugs has been immense. If you look at the latest generation of pain drugs, it has cost billions of dollars.

“That has scared off companies and I think companies are more focused on areas where the returns are better from a pricing point of view. Because quite frankly, if you look at oncology you can get (drug) prices that are far better than for pain.”

Insurers Refuse to Pay for New Treatments

Another problem is insurance coverage. A few years ago the U.S. Food and Drug Administration pressured drug makers to develop abuse deterrent technology for opioids to reduce the risk of abuse and addiction. Some companies spent hundreds of millions of dollars developing abuse deterrent opioids that insurers now refuse to pay for because they are more expensive.

“Payers are a huge barrier to innovative therapies because they block coverage. Without insurance coverage there is little incentive to invest,” said Lynn Webster, MD, a leading expert and researcher in pain management, who is vice president of Scientific Affairs at PRA Health Sciences. 

“In the past 30 years there haven't been more than 3 new chemical entities approved by the FDA. One reason is that we don't understand enough about the different mechanisms generating pain,” Webster explained. “I see our current approach is similar to how cancer research was conducted 60 years ago.  Back then most cancers were treated with the same monotherapies.  Once research delved into the multi-mechanistic contributions to cancer, therapeutic advances were possible. We need to do the same for pain. And insurance has to pay for the innovations.”

“Pain is unfortunately penalized by society. People feel there is enough treatment available,” said Grünenthal’s Baertschi. “There are a lot of very good pain therapies out there. But there are quite a few areas, especially niche areas and specific pain types, that are not being treated adequately and that’s where we focus our research.”

One analyst said it is unlikely Congress will go along with the proposed cuts in the NIH budget because it funds politically popular programs.

"At worst, we believe NIH (funding) will remain flat in a continuing resolution if there is a government spending standoff," wrote Cowen analyst Doug Schenkel in a note to investors. "Although NIH funding hasn't kept up with inflation, the only time there were cuts to the agency in the past decade was when Congress' hand was forced by sequestration."

A Coalition to Save NIH Funding has also been formed to lobby against the budget cuts.

"We were dismayed to learn that the NIH is vulnerable to deep funding cuts," said Carrie Jones of JPA Health Communications, which is managing the coalition. "Each day America benefits from the innovation and scientific discoveries made at the NIH. We won't sit idly by and watch critical research be stifled."