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.”