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.

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."

Doctors and Pain Patients Often Disagree on Goals

By Pat Anson, Editor

If you’ve ever felt that you and your doctor are not on the same page when it comes to treating your chronic pain, you’re not alone.

A small study published in The Clinical Journal of Pain found that disagreements between primary care physicians and patients over priorities in pain management are common. Patients generally hope to reduce pain intensity and identify the pain’s cause, while physicians aim to improve physical function and reduce the side effects of opioid pain medication, such as dependency.

"We wanted to understand why discussions about pain between patients and doctors are often contentious and unproductive," said lead author Stephen Henry, MD, an assistant professor of internal medicine at University of California Davis.

"Primary care physicians treat the majority of patients with chronic pain, but they aren't always equipped to establish clear, shared treatment goals with their patients."

The study involved 87 patients receiving opioid prescriptions for chronic musculoskeletal pain and 49 internal or family medicine physicians at two UC Davis Medical Center clinics in Sacramento, California. In most cases, the patients were seeing their regular physicians. Patients receiving pain treatment as part of cancer or palliative care were excluded from the study.

Immediately following clinic visits between November 2014 and January 2016, the patients completed questionnaires to rate their experiences and rank their goals for pain management. The physicians also completed questionnaires about the level of visit difficulty, along with their own rankings of goals for the patient's pain management.

Nearly half of patients (48%) ranked reducing pain intensity as their top priority, while 22% said finding a diagnosis was most important to them. In contrast, physicians ranked improving physical function as the top priority for 41% of patients, while reducing medication side effects was most important for 26 percent of them.

Physicians also rated 41% of the visits with pain patients as "difficult" -- meaning their interactions were challenging or emotionally taxing. Primary care physicians usually rate about 15% of patient visits as difficult.

One surprise finding was that patients rated their office visits as fairly positive, even when their doctor did not. That may reflect the fact that patients tend to have positive relationships with their regular physicians, even though they don't always agree with them..

“Another possibility is that patients and physicians may not have realized that they prioritized different goals, because goals were not explicitly discussed during the visit. Some patients may assume that their treatment priority and their physicians’ treatment priority are the same, even when they are not,” Henry wrote. “Disagreements about goals may only become relevant during visits where patients and physicians disagree about treatment plans (e.g., whether to prescribe opioids).”

Henry says primary care physicians may have adapted to recommendations such as the CDC opioid guidelines, which emphasize functional goals and avoidance of long-term opioid therapy. Patients have yet to adapt to the guidelines and are still primarily interested in pain relief.

What can be done to help doctors communicate more effectively with their pain patients?

Henry recommends communication training for primary care physicians to ensure that patients are more aware of their goals. "It is critical for doctors and patients to be on the same page and not working at cross purposes," he said.

Bacteria Studies Give New Hope to IBD Patients

By Pat Anson, Editor

A new study is adding to the growing body of evidence linking gut bacteria to autoimmune and gastrointestinal diseases – research that could lead to new and more effective treatments.

Researchers at the University of Utah used animal studies to show that a certain type of yeast can aggravate symptoms of Inflammatory Bowel Disease (IBD). Their findings, published in the journal Science Translational Medicine, also suggest that allopurinol, a generic drug already on the market, could offer some relief.

IBD is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract, causing diarrhea, pain, fatigue and weight loss.

For years doctors have used the presence of yeast antibodies, specifically antibodies in the yeast Saccharomyces cerevisiae, to differentiate between Crohn’s disease and ulcerative colitis, two variations of IBD. But it was unclear the role that yeast played in relation to IBD.

“To me this was a huge hole in our understanding of the role of yeast in IBD and our health,” said June Round, PhD, an associate professor in pathology at the University of Utah School of Medicine.

Round and her research team studied two types of yeast that are common in healthy people and IBD patients. Saccharomyces cerevisiae, also called Baker’s yeast, is a prominent organism in the environment and in our food. Rhodotorula aurantiaca is also commonly found in the environment, as well as milk and fruit juice.

Scientists gave each type of yeast to laboratory mice that had been treated with chemicals to induce IBD-like symptoms. The symptoms worsened in mice fed S. cerevisiae, but not in those fed R aurantiaca.

“The mice fed S. cerevisiae experienced significant weight loss, diarrhea, bloody stool, just like a person with IBD,” said Tyson Chiaro, graduate student in Round’s lab.

Further study revealed that the mice fed S. cerevisiae had a higher concentration of nitrogen-rich compounds, called purines, than the mice fed R. aurantiaca. Unlike other yeasts, S. cerevisiae cannot break down purines that accumulate in the intestinal tract and produce uric acid. Uric acid exacerbates inflammation, which may worsen IBD symptoms.

When the mice were treated with allopurinol, a medication used to block the production of uric acid in gout patients, the drug significantly reduced their intestinal inflammation.

“Our work suggests that if we can block the mechanism leading to the production of uric acid, perhaps with allopurinol, IBD patients with a high concentration of S. cerevisiae antibodies may have a new treatment option to reduce inflammation, which could allow the intestine time to heal,” said Round.

E. Coli linked to IBD and spondyloarthritis

Another recent study has helped researchers identify E. coli bacteria found in people with Crohn's disease that can trigger inflammation associated with spondyloarthritis, a painful arthritic condition that affects the spine and joints.

Researchers used fecal samples from IBD patients to identify bacteria in the gut that were coated with antibodies called immunoglobulin-A (IgA) that fight infection. Using flow cytometry, in which fluorescent probes are used to detect IgA-coated bacteria, the researchers found the E. coli bacteria were abundant in fecal samples from patients with both Crohn's disease and spondyloarthritis.

"Our findings may allow us to develop diagnostic tools to stratify Crohn's patients with spondyloarthritis symptoms as well as patients at risk," said senior author Dr. Randy Longman, an assistant professor of medicine and director of the Jill Roberts Institute Longman Lab at Weill Cornell Medicine.

Longman and his research team found that patients with Crohn's disease and spondyloarthritis had high levels of Th17 cells, which help fight inflammation. The finding may help physicians select therapies that target inflammation in both the bowels and the joints.

"We knew there was smoke but we didn't know where the fire was," said Dr. Kenneth Simpson, a professor of small animal medicine at Cornell's College of Veterinary Medicine. "If we can block the ability of bacteria to induce inflammation, we may be able to kick Crohn's disease and spondyloarthritis into remission."

The study findings are also published in Science Translational Medicine

What Cavemen Used for Pain Relief

By Pat Anson, Editor

Neanderthals may be a lot smarter than we give them credit for. Especially when it comes to finding pain relief.

Ancient DNA extracted from the dental plaque of Neanderthals has revealed new insights into their behavior and diet, including their use of plant-based medicine to treat pain and illness.

An international team of researchers compared dental plaque from the jawbones of four Neanderthals found at ancient cave sites in Belgium (Spy Cave) and Spain (El Sidrón Cave). The four samples range from 42,000 to around 50,000 years old and are the oldest dental plaque ever to be genetically analyzed.

“Dental plaque traps microorganisms that lived in the mouth and pathogens found in the respiratory and gastrointestinal tract, as well as bits of food stuck in the teeth – preserving the DNA for thousands of years,” says Dr. Laura Weyrich, a research fellow at the University of Adelaide’s Australian Centre for Ancient DNA (ACAD), who was lead author of the groundbreaking study reported in the journal Nature.

RESEARCHERS IN EL SIDRON CAVE

“Genetic analysis of that DNA ‘locked-up’ in plaque, represents a unique window into Neanderthal lifestyle – revealing new details of what they ate, what their health was like and how the environment impacted their behavior.”

The researchers found that Neanderthals from Spy Cave were mostly meat eaters who consumed wooly rhinoceros and wild sheep, and supplemented their diet with wild mushrooms.

“Those from El Sidrón Cave on the other hand showed no evidence for meat consumption, but appeared instead to have a largely vegetarian diet, comprising pine nuts, moss, mushrooms and tree bark – showing quite different lifestyles between the two groups,” said professor Alan Cooper, Director of ACAD.

The analysis of one Neanderthal found at El Sidrón revealed another surprise. He probably had pain from a dental abscess on his jawbone, and also had signs of an intestinal parasite that causes acute diarrhea.

“Clearly he was quite sick. He was eating poplar, which contains the pain killer salicylic acid, and we could also detect a natural antibiotic mold not seen in the other specimens,” said Cooper. “Apparently, Neanderthals possessed a good knowledge of medicinal plants and their various anti-inflammatory and pain-relieving properties, and seem to be self-medicating.”

Salicylic acid is the active ingredient in aspirin; while certain types of mold – such as Penicillium – help the body fight off infections.

JAWBONE OF NEANDERTHAL FOUND IN EL SIDRON CAVE

“The use of antibiotics would be very surprising, as this is more than 40,000 years before we developed penicillin. Certainly our findings contrast markedly with the rather simplistic view of our ancient relatives in popular imagination,” says Cooper.

The researchers also found that Neanderthals and modern humans shared several disease-causing microbes, including the bacteria that cause dental cavities and gum disease.

Types of bacteria were closely associated with the amount of meat in the diet, with the Spanish Neanderthals grouping with ancient human ancestors in Africa. In contrast, the Belgian Neanderthal bacteria were similar to early hunter gatherers, and quite close to modern humans and early farmers.

“Not only can we now access direct evidence of what our ancestors were eating, but differences in diet and lifestyle also seem to be reflected in the commensal bacteria that lived in the mouths of both Neanderthals and modern humans,” said Professor Keith Dobney of the University of Liverpool.

“Major changes in what we eat have, however, significantly altered the balance of these microbial communities over thousands of years, which in turn continue to have fundamental consequences for our own health and well-being. This extraordinary window on the past is providing us with new ways to explore and understand our evolutionary history through the microorganisms that lived in us and with us.”

Why Women Feel Chronic Pain More Than Men

By Pat Anson, Editor

A new study may help explain why women are more likely to have chronic pain and are more sensitive to painful sensations than men.

It’s because their brains work differently.

In experiments on laboratory animals, researchers at Georgia State University found that immune cells in female rats are more active in regions of the brain involved in pain processing. Their study, published in the Journal of Neuroscience, found that when microglia cells in the brain were blocked, the female rats responded better to opioid pain medication and matched the levels of pain relief normally seen in males.

Women suffer from a higher incidence of chronic pain conditions such as fibromyalgia and osteoarthritis. And studies have found that they often have to take more morphine than men to get the same level of analgesia.

“Indeed, both clinical and preclinical studies report that females require almost twice as much morphine as males to produce comparable pain relief,” says Hillary Doyle, a graduate student in the Neuroscience Institute of Georgia State. “Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia.”

In healthy people, microglia cells survey the brain, looking for signs of infection or pathogens like bacteria. Morphine is perceived as a pathogen and activates the cells, causing the release of inflammatory chemicals such as cytokines. Researchers say this causes "a neuroinflammatory response that directly opposes the analgesic effects of morphine."

To test their theory, researchers gave male and female rats naloxone, a drug that reverses the effects of an opioid overdose, and found that it inhibits the microglia activation triggered by morphine.

“The results of the study have important implications for the treatment of pain, and suggests that microglia may be an important drug target to improve opioid pain relief in women,” said Dr. Anne Murphy, PhD, co-author of the study and associate professor in the Neuroscience Institute at Georgia State.

Murphy says her team’s finding may also help explain why women are significantly more likely to experience chronic pain conditions than men.

A recent study at UCLA and UC Irvine found that microglial cells in both female and male rats can be activated by chronic pain.  The researchers found that brain inflammation in rodents caused by chronic nerve pain led to accelerated growth of microglia. The cells triggered chemical signals in the brain that restricted the release of dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers.

Early Detection and Diet May Help Prevent Osteoporosis

By Pat Anson, Editor

The key to good bone health – and preventing fractures later in life – may lie in anti-inflammatory diets and earlier detection of bone loss, according to two new studies.

Researchers at the University of Michigan are studying new ways to identify women at risk of osteoporosis, a loss in bone density that raises the risk of fractures and disability. Breaking a bone in your spine or hip doubles your chances of developing chronic widespread body pain, especially if you are older.

"It's been considered a silent disease," says Karl Jepsen, PhD, associate chair of research and professor of orthopaedic surgery at Michigan Medicine. "One of the biggest challenges when you're looking at age-related bone fragility is to identify people who will fracture."

Jepsen is the lead author of a study published in the Journal of Bone and Mineral Research, which followed nearly 200 women for 14 years as they transitioned through menopause.

"Current identification for bone fragility takes place when the patient is around 65 years of age," Jepsen explains.

"We were hopeful that this study would give us an opportunity to identify those patients as early as 30 years before they fracture based on their bone traits. That means we would have an opportunity to intervene before the fracture happens, instead of after the fact."

Jepsen and his colleagues started following the women in 1996. Participants who enrolled had to be between 42 and 52 years of age and had at least one menstrual period in the previous three months. The women had bone density scans and other tests annually to measure changes in their bone mineral density.

Researchers found that the women experienced a wide variation in bone mineral content and bone area within the hip as they went through menopause, a finding that was unexpected.

"Our results were opposite to all expectations of how we assumed this would work," Jepsen says. "We found some women appeared to have hip bones that were increasing in strength during the menopausal transition while others seemed to be losing strength."

Jepsen said his study demonstrates that bone changes can be tracked individually in women during menopause, when treatment can begin earlier to prevent bone loss. Hormones and bisphosphonate drugs are currently used to help strengthen bones.

“Our goal is to use simple bone traits to identify those women that may benefit from early intervention when it comes to bone fragility, instead of the current strategy, which treats individuals after they have lost appreciable bone mass and strength," he said.

Anti-Inflammatory Diet Improves Bone Health

Anti-inflammatory diets -- which tend to be high in vegetables, fruits, fish and whole grains -- could boost bone health and prevent fractures, according to a study at The Ohio State University.

Researchers analyzed dietary data from over 160,000 women enrolled in the landmark Women's Health Initiative by assigning inflammation scores based on 32 foods that the women reported consuming. Researchers also looked at bone-mineral-density data from over 10,000 women and collected fracture data for the entire study group.

They found a correlation between high-inflammatory diets and fractures in post-menopausal younger than 63. Women with the least-inflammatory diets also lost less bone mineral density.

"This suggests that as women age, healthy diets are impacting their bones," said Tonya Orchard, an assistant professor of human nutrition at Ohio State's Food Innovation Center. "These women with healthier diets didn't lose bone as quickly as those with high-inflammation diets, and this is important because after menopause women see a drastic loss in bone density that contributes to fractures,"

The study, which appears in the Journal of Bone and Mineral Research, was observational -- meaning it does not definitively link diet to bone health. But it adds to a growing body of evidence that inflammation can increase osteoporosis risk.

"By looking at the full diet rather than individual nutrients, these data provide a foundation for studying how components of the diet might interact to provide benefit and better inform women's health and lifestyle choices," said Rebecca Jackson, the study's senior author and director of Ohio State's Center for Clinical and Translational Science.

Previous studies have connected high levels of inflammatory markers in the blood to bone loss and fractures in older women and men. The new findings suggest that women's bone health could benefit when they choose a diet higher in beneficial fats, plants and whole grains.