Researchers Say Brain Processes Pain Emotionally

By Pat Anson, Editor

Many chronic pain sufferers resent being told their pain is “all in your head” or that they’re being too emotional about their pain.

But tests conducted by German researchers suggest that the human brain begins to shift from sensory to emotional processing of pain after just a few minutes of painful stimuli.

Scientists at Technische Universität München (TUM) in Munich enrolled 41 people in a study to measure brain activity as they were exposed to painful heat stimulation of a hand. Participants wore a cap with 64 electrodes that measured nerve cell activity in the brain throughout the experiment. The electroencephalograms (EEGs) made it possible to pinpoint which nerve cells respond to pain.

Participants were then given painful heat stimuli to the hand for ten minutes, with the intensity of the heat varying throughout the experiment. The test subjects were asked to continuously assess the level of their pain on a scale of one to a hundred with the other hand using a slider.

"We were absolutely amazed by the results. After just a few minutes, the subjective perception of pain changed. For example, the subjects felt changes in pain when the objective stimulus remained unchanged. The sensation of pain became detached from the objective stimulus after just a few minutes," said Markus Ploner, MD, a professor for human pain research at the TUM School of Medicine.

Previous studies have shown that brief pain stimulation is predominantly processed by sensory areas of the brain that process signals from nerves in the skin. However, in the heat experiment with longer-lasting pain, the EEGs showed that emotional areas of the brain became active.

"If pain persists over a prolonged period of time, the associated brain activity shows that it changes from a pure perception process to a more emotional process. This realization is extremely interesting for the diagnosis and treatment of chronic pain where pain persists for months and years," explained Ploner.

A second experiment showed that it is not just the duration, but also the anticipation of pain that affects perception. Twenty test subjects were given different intensities of painful laser pulses on two areas of the back of the hand. The participants then verbally rated how strong they perceived the pain to be.

In a second round of testing, the subjects were again given the same stimuli, but this time with two creams applied to both hand areas. Although neither cream contained an analgesic, the subjects were told that one of the creams had a pain-relieving effect.

Researchers found the cream had a placebo effect.

"The subjects assessed the pain on the skin area with the allegedly pain-relieving cream as significantly lower than on the other area of skin," said Ploner.

In addition to feeling less pain, the EEGs showed that nerve cells triggered a different pattern of brain activity.

"Our results show how differently our brain processes the same pain stimuli. Systematically mapping and better understanding this complex neurological phenomenon of 'pain' in the brain is a big challenge, but is absolutely essential for improving therapeutic options for pain patients," added Ploner.

Counseling and Behavioral Therapy Help Vets in Chronic Pain

By Pat Anson, Editor

An innovative two-step program that combines analgesics with deep breathing, relaxation techniques and counseling significantly reduced pain levels in U.S. military veterans who suffer from chronic pain, according to a new study at a VA Medical Center.

Researchers at the Roudebush VA Medical Center in Indianapolis, the Regenstrief Institute and the Indiana University School of Medicine studied 241 veterans who returned from deployments in Iraq and Afghanistan. Findings from the ESCAPE trial -- short for Evaluation of Stepped Care for Chronic Pain – are being published in JAMA Internal Medicine.

It is a critical health issue among veterans, many of whom had multiple, often lengthy deployments. Many have significant long-term pain. We know that medications alone are only modestly successful in helping them; current pain treatments haven't made much of a dent,” said Matthew Blair, MD, the study’s lead investigator and an associate professor of medicine at Indiana University.

A recent study found that nearly half of the American soldiers deployed to Iraq and Afghanistan return home to the U.S. in chronic pain, and about one in seven were using opioid pain relievers. Although pain is a common condition, researchers say no intervention studies had been conducted on the best ways to treat chronic pain in these veterans.

“The absence of studies is concerning because chronic pain may prove even more disabling in veterans of recent conflicts than in veterans of previous eras owing to the high combat intensity,” said Bair, who served for eight years as a U.S. Army physician.

The veterans in the ESCAPE study suffered from moderate to severe chronic pain in the back, knee, neck or shoulder for at least three months. Veterans with substance or abuse problems were excluded from the study, as were those with suicidal thoughts, active psychosis or schizophrenia.

In the first phase of ESCAPE, patients were given 12 weeks of pain medication, ranging from acetaminophen to opioids. Because analgesics may not relieve pain sufficiently when used alone, the veterans were educated about self-management strategies such as goal setting, problem solving, deep breathing and relaxation techniques. Patients were also encouraged to minimize bed rest, return to normal activities, and perform stretching and strengthening exercises.

Step two involved 12 weeks of cognitive behavioral therapy that included psychological counseling for both pain and depression. Nurse care managers consulted with veterans over the telephone, helping them counter negative thoughts – such as helping them understand that while they may not be able to perform the same physical activities they enjoyed before deployment, a substitute activity like swimming might be achievable and decrease their pain.

Those who received the two-step ESCAPE program saw improvement in their function and a decrease in pain severity and pain interference -- how pain interferes with their mood, physical activity, work, relationships, sleep and enjoyment of life.

“The decrease in pain severity and 30 percent improvement in pain-related disability we achieved in the ESCAPE study are clinically significant, and we found that improvement lasted for at least nine months," said Blair.

Researchers say the ESCAPE program could be duplicated to treat chronic pain at other VA medical centers and other large health care systems outside the VA. However, implementing the program in smaller community settings or in private settings may be challenging.

"This is an important, methodologically rigorous study that underscores the value of psychobehavioral treatment in chronic pain,” said Beth Darnall, PhD, a pain psychologist and author of Less Pain, Fewer Pills. “Cognitive-behavioral therapy and the use of relaxation strategies work exceedingly well within the context of a comprehensive pain management program, and when the techniques are used regularly.”

Darnall recommends the same techniques used in the VA study in her own private practice.

“It’s important for people to know that the results from psychobehavioral skills build over time.  In other words, use them daily and your results will unfold and strengthen over the course of weeks and months,” she wrote in an email to Pain News Network.

Time for a More Rational Cannabis Policy

By Lynn R. Webster, MD, Guest Columnist

Individuals who suffer from severe chronic pain are caught in a double bind. Opioids contribute to the enormous societal harms of unintentional overdose, diversion and addiction, and data on their long-term effectiveness are conflicting and inadequate. But for patients who are helped by opioids, policies and regulations to address societal harms are, in some cases, impeding access to treatment, making it difficult even to find a knowledgeable physician. The need for safer and more effective analgesics has never been greater.

Answers do not lie in pitting one serious disease (i.e., chronic pain) against another (i.e., addiction) but in seeking scientific breakthroughs that lead to serious analgesic benefits without addictive properties or risk for respiratory depression. Rigorous research of cannabinoids has the potential to unlock a medicinal benefit on a societal scale. But committing to the necessary research requires rethinking how we classify cannabinoids as a controlled substance.

Inching Toward Safer Pain Treatments

Tetrahydrocannabinol (THC) produces the “high” effect associated with marijuana. On its own, cannabidiol (CBD) displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, anti-inflammatory and neuroprotective properties, and is believed to have fewer undesirable psychoactive effects than THC. Practically speaking, harnessing the potential medicinal benefits of marijuana without these unwanted effects would be a long-awaited breakthrough for science. Despite many strictures, scientists -- largely from other countries -- are inching closer to the finish line with products that could replace opioids in some instances.

On this point, we must speak cautiously and with a clear understanding: The current literature is weak at best. For example, Sativex, an oral spray composed of CBD and delta-9-THC currently on the market in Europe, Canada and Mexico, did not meet its primary end point of statistical difference from placebo for relief of cancer pain in an initial Phase III trial. Research in this area is in a nascent stage, and the ultimate conclusions are uncertain. But conclusive evidence requires rigorous study at a far faster pace and greater volume than is currently possible. Therein lies the problem.

Sadly, research is stymied due, in large part, to a federal and state regulatory structure that hamstrings researchers from gaining access to legal supplies of THC/CBD for scientific purposes. To study cannabis in the United States, scientists must comply with the Controlled Substances Act of 1970, which classifies cannabinoids as a Schedule I drug. Scheduling is controlled by the Drug Enforcement Administration (DEA), and Schedule I drugs are deemed to have no medicinal value and a high potential for abuse. 

Because of this, a researcher must pass through a gauntlet of onerous and time-intensive requirements to gain access to cannabinoids. The requirements to secure a license with the DEA, to register with the FDA, and to comply with a long checklist of rules from the National Institute on Drug Abuse to obtain research-grade cannabis all conspire to make the process protracted and costly.

Yet the patchwork of public policy on marijuana is anything but consistent: 23 states and the District of Columbia have now legalized marijuana use in some form. Furthermore, public opinion is evolving to erase some of the historical stigma surrounding marijuana use.

Marathon runners have recently been using marijuana-infused balms and edible marijuana to treat pain and swelling. In a climate where it is now possible to ask in the pages of “Men’s Fitness,” “Does pot make you a better athlete?” the current classification of marijuana under Schedule I doesn’t make sense. Why define a substance as having no medical value when the evidence and the laws of many states now say otherwise? Reclassifying cannabinoids to Schedule II could help expand research opportunities and determine appropriate indications.

More importantly, rescheduling cannabinoids will not necessarily open the floodgates to irresponsible use. The American Society of Addiction Medicine warns that marijuana is not benign but a psychoactive drug with risks for abuse and addiction and subject to a risk–benefit profile discussion with patients in clinical settings. Rightly, Schedule II drugs are recognized as having a high potential for abuse and dependence and are heavily regulated. Thus, rescheduling would still recognize risks associated with cannabinoids in recreational use, while accepting that the potential medicinal benefits could help people suffering from a variety of diseases, including chronic pain. Given that opioids have significant risks as a medical treatment, including life-threatening respiratory depression, and have fueled a nationwide prescription drug abuse crisis, research to explore new pathways to analgesia-like cannabis would point us in a new and, we hope, better direction.

We cannot afford to wait. With more than 100 million Americans suffering from chronic pain annually—affecting more people than diabetes, heart disease, stroke and cancer combined, according to the Institute of Medicine—public policymakers must recognize and reschedule this potentially therapeutic modality.

Lynn R. Webster, MD, is Past President of the American Academy of Pain Medicine, and vice president of scientific affairs at PRA Health Sciences. He is a Pain Medicine News editorial board member and author of a forthcoming book, “The Painful Truth.” His blog can be found at lynnwebstermd.com. He lives in Salt Lake City. Follow him on Twitter @LynnRWebsterMD, Facebook and LinkedIn.

This column is republished with permission of Pain Medicine News.

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

Gene Therapy Lessens Pain of Diabetic Neuropathy (VIDEO)

By Pat Anson, Editor

An experimental gene therapy reduces pain and other symptoms by over 50 percent in patients with diabetic peripheral neuropathy, according to a new study at Northwestern University.

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.  Diabetic peripheral neuropathy (DPN) causes nerves to send out abnormal signals. Patients feel pain or loss of feeling in their toes, feet, legs, hands and arms. It may also include a persistent burning, tingling or prickling sensation. The condition can lead to injuries, chronic foot ulcers and even amputations.

Keith Wenckowski, who has type-one diabetes, says it felt “like walking on glass” when he walked barefoot in sand.   

Wenckowski and 83 other participants in the Northwestern study received two low doses of a non-viral gene therapy called VM202. They went to a clinic twice in a two-week period for a series of injections into their calf muscles and lower legs. Some received injections of a saline placebo, others a low dose of the therapy and others a higher dose.

"Those who received the therapy reported more than a 50 percent reduction in their symptoms and virtually no side effects," said Dr. Jack Kessler, lead author of the study. "Not only did it improve their pain, it also improved their ability to perceive a very, very light touch."

After three months, patients in the low-dose group experienced a significant reduction in pain compared to the placebo group. The effect persisted at six and nine months in the low-dose group.

"I can now go to a beach and walk on the sand without feeling like I am walking on glass," says Wenckowski, more than a year after receiving the therapy. "I am hoping the effects I am feeling do not cease."

VM202 contains the human hepatocyte growth factor (HGF) gene. Growth factor is a naturally occurring protein in the body that acts on nerve cell to keep them alive, healthy and functioning. Future studies will investigate if the therapy can actually regenerate damaged nerves and reverse the neuropathy.

Patients with the most extreme form of the DPN feel intense pain with a slight graze or touch. The pain can interfere with daily activities, sleep, mood and can diminish quality of life. Many drugs used to treat DPN, such as Neurontin and Lyrica, either don’t work or have unpleasant side effects.

"We are hoping that the treatment will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and therefore reduce the pain," said Senda Ajroud-Driss, MD, an attending physician at Northwestern Memorial Hospital and an author of the study.

"We found that the patients who received the low dose had a better reduction in pain than the people who received the high dose or the placebo. Side effects were limited to injection site reaction."

The results of this Phase II, double-blind, placebo-controlled study are being published in the journal Annals of Clinical and Translation Neurology.A future, much larger Phase III study will soon be underway.

"Right now there is no medication that can reverse neuropathy," Kessler said. "Our goal is to develop a treatment. If we can show with more patients that this is a very real phenomenon, then we can show we have not only improved the symptoms of the disease, namely the pain, but we have actually improved function."

Spider Venom Could Take the Sting Out of Chronic Pain

By Pat Anson, Editor

Black widow spiders are well known for their dangerous, painful and sometimes even lethal bites. The venom of a female black widow is 15 times as toxic as a rattlesnake’s.

But that venom also contains an ingredient that could be developed into a new class of potent painkilllers.

Researchers in Australia have identified seven compounds in the venom of spiders that block the body's ability to send signals to the brain through what is called the pain pathway – also known as Nav 1.7 channels.

"A compound that blocks Nav 1.7 channels is of particular interest for us. Previous research shows indifference to pain among people who lack Nav 1.7 channels due to a naturally-occurring genetic mutation - so blocking these channels has the potential of turning off pain in people with normal pain pathways," said study leader Glenn King, PhD, of The University of Queensland's Institute for Molecular Bioscience.

King and his colleagues built a system that can rapidly analyze the protein molecules in spider venoms. They studied the venom of over 200 spider species and found that 40% of the venoms contained at least one compound that blocked human Nav 1.7 channels. Of the seven promising compounds identified so far, one is particularly potent and has a chemical structure that suggests it has a high level of chemical, thermal, and biological stability, which would be essential for administering in a new medicine.

"Untapping this natural source of new medicines brings a distinct hope of accelerating the development of a new class of painkillers that can help people who suffer from chronic pain that cannot be treated with current treatment options," said researcher Julie Kaae Klint, PhD.

Researchers have only scratched the surface. There are over 45,000 species of spiders, many of which kill their prey with venoms that contain hundreds - or even thousands - of protein molecules that block nerve activity.

"A conservative estimate indicates that there are nine million spider-venom peptides, and only 0.01% of this vast pharmacological landscape has been explored so far," says Klint.

The study is published in the British Journal of Pharmacology.

Researchers are also studying the potential of venom in cone snails for its potential for blocking pain signals in humans. German scientists at the Pharmaceutical Institute of the University of Bonn say one advantage of the peptides found in snail venom is that they decompose quickly and are unlikely to cause dependency.

A pharmaceutical drug derived from cone snail neurotoxins has already been developed and marketed under the brand name Prialt. The drug is injected in spinal cord fluid to treat severe pain caused by failed back surgery, injury, AIDS, and cancer.

Mornings Worst for Lower Back Pain

By Pat Anson, Editor

People who suffer from lower back pain are significantly more likely to feel their first aches and pains after waking up in the morning, according to researchers in Australia.

Their study, which was published in the journal Arthritis Care & Research, found a variety of physical and psychosocial triggers that increase the risk of low back pain. People engaged in manual tasks involving awkward positions are eight times more likely to suffer from back pain, while people who are distracted or fatigued during activities were about four times more likely.

"Understanding which risk factors contribute to back pain and controlling exposure to these risks is an important first step in prevention," explains Manuela Ferreira, PhD, an associate professor at Sydney Medical School at The University of Sydney in New South Wales, Australia. "Our study is the first to examine brief exposure to a range of modifiable triggers for an acute episode of low back pain."

Researchers recruited nearly 1,000 participants from 300 primary care clinics in Sydney, Australia, who had acute low back pain. They were asked to self-report on a dozen physical or psychosocial factors in the 96 hours prior to the onset of their back pain.

The risk of a new episode of low back pain varied significantly depending on a range of triggers. Moderate to vigorous physical activity nearly tripled the risk of low back pain, while being distracted during an activity made participants 25 times more likely to have back pain.

Researchers recruited nearly 1,000 participants from 300 primary care clinics in Sydney, Australia, who had acute low back pain. They were asked to self-report on a dozen physical or psychosocial factors in the 96 hours prior to the onset of their back pain.

The risk of a new episode of low back pain varied significantly depending on a range of triggers. Moderate to vigorous physical activity nearly tripled the risk of low back pain, while being distracted during an activity made participants 25 times more likely to have back pain.

One finding not reported previously was that back pain risk was highest between 7:00 a.m. and noon. Ferreira believes that may be because people are not fully alert and discs in the spine may be more susceptible to damage in the morning.

One surprise finding is that growing older appears to moderate the risk of back pain caused by lifting heavy loads. The risk was 13.6 times higher for people at age 20. At age 40 it was 6.0 and at 60 years of age the risk was only 2.7 times higher.

Alcohol and sex appeared to have no association lower back pain.

"Understanding which modifiable risk factors lead to low back pain is an important step toward controlling a condition that affects so many worldwide," said Ferreira. "Our findings enhance knowledge of low back pain triggers and will assist the development of new prevention programs that can reduce suffering from this potentially disabling condition."

Lower back pain is the leading cause of disability worldwide, with nearly 10% of the world's population experiencing back pain at some point in their lives. Low back pain has a greater impact on global health than malaria, diabetes, or lung cancer; yet little progress has been made to identify effective prevention strategies.

Lower back pain is not usually linked to a serious disease. It can be triggered by everyday activities, including bad posture, bending awkwardly, lifting incorrectly or standing for long periods of time.

Study Finds Acupuncture Has Placebo Effect

By Pat Anson, Editor

When it comes to acupuncture, perception apparently does matter.

British researchers found in a new study that people with back pain who believe acupuncture will not help or do little to relieve their symptoms will gain less benefit from treatment than people who believe it works.

And people who feel they can manage their back pain have less disability as a result of acupuncture treatment.

“They experienced less disability over the course of treatment when they came to see their back pain as more controllable, when they felt they had better understanding of their back pain, when they felt better able to cope with it, were less emotional about it, and when they felt their back pain was going to have less of an impact on their lives," said Felicity Bishop, PhD, an Arthritis Research UK career development fellow.

Bishop and her colleagues at the University of Southampton wanted to find out why some people with back pain gain more benefit from acupuncture than others. They recruited 485 people with back pain and asked them to complete questionnaires before they saw an acupuncturist; as well as two weeks, three months and six months after starting treatment. The questions measured psychological factors, clinical and demographic characteristics, and back-related disability.

The study, which was funded by Arthritis Research UK, is being published in The Journal of Clinical Pain.

"The analysis showed that psychological factors were consistently associated with back-related disability," said Bishop, who believes acupuncturists should consider helping patients think more positively about their back pain as part of their treatment.

"People who started out with very low expectations of acupuncture -- who thought it probably would not help them -- were more likely to report less benefit as treatment went on,” she said.

Previous research has shown that many factors -- other than the insertion of needles – can play a role in the effectiveness of acupuncture, such as the relationship that the patient develops with the acupuncturist and the patient's belief about acupuncture.

"This study emphasises the influence of the placebo effect on pain. The process whereby the brain's processing of different emotions in relation to their treatment can influence outcome is a really important area for research,” said Dr. Stephen Simpson, director of research at Arthritis Research UK.

Acupuncture, which was originally developed as part of traditional Chinese medicine, is one of the most widely practiced forms of alternative medicine. As many as 3 million Americans receive acupuncture treatments, most often for relief of chronic pain.

While there is little consensus in the medical community about acupuncture’s value, a study in the Archives of Internal Medicine found that relief offered by acupuncture is real and should be considered a viable form of treatment .

Focusing on patients who reported chronic back and neck pain, osteoarthritis, chronic headache and shoulder pain, researchers at Memorial Sloan-Kettering Cancer Center in New York conducted a meta-analysis (a study of studies) of 29 studies involving nearly 18,000 adults.

“Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo,” the study concluded. “However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.