New proposal for the management of low back pain with a proprioceptive approach

 Ever since the early humans learned to walk upright, they have suffered, as an unfortunate consequence of their erect posture, from low back pain. Modern understanding on this matter dictates that low back pain, in particular, is caused due to a postural instability resulting from poor "proprioception," which is a term for the perception of part of our body's own position in space. In fact, our trunk and lower legs are key to maintaining postural stability due to the presence of "proprioceptors" -- sensory receptors responding to position and movement -- in those areas.

Elderly people suffering from low back pain tend to have poorly performing proprioceptors, which is thought to affect their "proprioceptive control strategy" -- a postural control strategy in response to vibratory stimulations as proprioceptive input. Interestingly, studies have suggested that a local vibratory stimulation can, in fact, improve proprioceptive function. In previous studies by other researchers, however, its effect on postural control is still unclear. Moreover, the studies make no distinction between poor and healthy proprioceptors and do not take into account the fact that each proprioceptor has a natural vibration response frequency.

To address these issues, a team of researchers from Japan recently conducted a study in which they explored the effect of local vibratory stimulations on the proprioceptive control strategy when applied to a poor proprioceptor. Prof. Yoshifumi Morita from Nagoya Institute of Technology, Japan, who was part of the study, published in Electronics, lays down the research question: "For elderly people with low back pain, can proprioceptive function be improved? Will it cure the low back pain?"

Researchers carried out their study over a period of 3 months in which they recruited six elderly individuals, all of whom were patients with low back pain. Researchers made each participant stand on a balance board to assess their standing balance and attached fasteners with vibrators to their legs as well as both sides of their trunk. They then generated vibration signals using a PC and amplified and output them from the vibrators as mechanical vibratory stimulations. Furthermore, they allowed the frequency of stimulation to vary with time, from an initial 20 Hz (cycles/second) up to 300 Hz, to gauge the postural response as a function of the applied frequency. Finally, they compared the proprioceptive control strategy in each patient before and after applying the stimulations to an impaired proprioceptor.

Three patients showed an improvement in their proprioceptive control strategy after their impaired muscle spindles (proprioceptor detecting stretch in muscles) responded to higher frequency, an observation that suggested that low back pain could be alleviated in patients by activating impaired proprioceptors with vibratory stimulations. Furthermore, the treatment device and protocol could be used for multiple frequency ranges, allowing for the diagnosis as well as activation of a poor proprioceptor.

Given the results, the researchers look forward to conducting a clinical trial for a larger group of patients. "The clinical trial is scheduled to start in April this year and will be conducted for the next three years. We plan to verify whether the improved proprioceptive sensation can be maintained for a long time, thus relieving elderly people of low back pain," comments an excited Prof. Morita.

The team hopes that the trial's findings will soon lead to the commercialization of their device, which will allow elderly patients with low back pain to finally breathe a huge sigh of relief!

Source: ScienceDaily

Soft tissue destruction and lower back pain

 Back pain affects many people at some point in their lives, and a common cause is damage to the squishy discs or flexible, rubbery tissues of the spine. However, observing this damage at an early stage is difficult with current imaging methods. Now, researchers reporting in ACS Nano can see microscopic soft tissue destruction in animal spines by targeting denatured collagen with fluorescent molecules. 

Anywhere along the spine, from the neck to tail bone, can become uncomfortable when its soft and protective tissues, including the cartilage and jelly-like intervertebral discs, become damaged and lose their structure. Daily wear-and-tear, as well as some disorders, such as facet joint osteoarthritis or ankylosing spondylitis, can degrade and unfurl the collagen proteins that give these tissues their bounce and flexibility. Detecting compromised collagen early could help patients get relief before the pain becomes severe, but this is very difficult to do with existing medical technologies, such as X-rays and magnetic resonance imaging (MRI). Previously, Yang Li and colleagues developed a collagen hybridizing peptide (CHP) probe that specifically binds unfurled collagen molecules, which happens when they deteriorate and lose their ability to cushion vertebrae. So, Li, Kuibo Zhang, Hong Shan and colleagues wanted to test if CHP labeled with fluorescent tags could be used as an imaging method to identify collagen destruction in the body.

To make the peptide probe more stable in the body, the researchers modified CHP by substituting a hydroxyl group with fluorine and then attaching a fluorescent dye to it. When healthy mice and rats were injected with the fluorescent dye-labeled CHP and imaged with near-infrared fluorescence (NIRF), the team could confirm that the fluorescing molecules accumulated on the soft tissues between the vertebrae. Then the researchers removed a portion of the animals' spines and imaged them with light sheet fluorescence microscopy. This technique produced precise 3D maps, which revealed denatured collagen. Because CHP is known to specifically target damaged collagen, the team says their imaging experiments show that even healthy animals can have a modest degree of deteriorated collagen around load-bearing joints, especially in the lower back. In additional experiments, both the NIRF images and 3D maps generated with the new method detected collagen deterioration in animal models of spinal injury before structural changes were visible in tissues on MRI scans. Finally, the researchers applied dye-labeled CHP as a stain to intervertebral disc slides from people that had undergone spinal surgeries. The fluorescence intensity of the stain rose substantially as the level of disc degeneration increased. Based on these results, the researchers say that their molecular-level technique could be developed in clinical studies for earlier diagnosis and targeted therapeutic treatments for patients with back pain.

SOurce: ScienceDaily

Back pain: Psychological treatment shown to yield strong, lasting pain relief, alter brain networks

 Rethinking what causes pain and how great of a threat it is can provide chronic pain patients with lasting relief and alter brain networks associated with pain processing, according to new University of Colorado Boulder-led research.

The study, published Sept. 29 in JAMA Psychiatry, found that two-thirds of chronic back pain patients who underwent a four-week psychological treatment called Pain Reprocessing Therapy (PRT) were pain-free or nearly pain-free post-treatment. And most maintained relief for one year.

The findings provide some of the strongest evidence yet that a psychological treatment can provide potent and durable relief for chronic pain, which afflicts one in five Americans.

"For a long time we have thought that chronic pain is due primarily to problems in the body, and most treatments to date have targeted that," said lead author Yoni Ashar, who conducted the study while earning his PhD in the Department of Psychology and Neuroscience at CU Boulder. "This treatment is based on the premise that the brain can generate pain in the absence of injury or after an injury has healed, and that people can unlearn that pain. Our study shows it works."

Misfiring neural pathways

Approximately 85% of people with chronic back pain have what is known as "primary pain," meaning tests are unable to identify a clear bodily source, such as tissue damage.

Misfiring neural pathways are at least partially to blame: Different brain regions -- including those associated with reward and fear -- activate more during episodes of chronic pain than acute pain, studies show. And among chronic pain patients, certain neural networks are sensitized to overreact to even mild stimuli.

If pain is a warning signal that something is wrong with the body, primary chronic pain, Ashar said, is "like a false alarm stuck in the 'on' position."

PRT seeks to turn off the alarm.

"The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it," said Ashar, now a postdoctoral researcher at Weill Cornell Medicine.

For the randomized controlled trial, Ashar and senior author Tor Wager, now the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College, recruited 151 men and women who had back pain for at least six months at an intensity of at least four on a scale of zero to 10.

Those in the treatment group completed an assessment followed by eight one-hour sessions of PRT, a technique developed by Los Angeles-based pain psychologist Alan Gordon. The goal: To educate the patient about the role of the brain in generating chronic pain; to help them reappraise their pain as they engage in movements they'd been afraid to do; and to help them address emotions that may exacerbate their pain.

Pain is not 'all in your head'

"This isn't suggesting that your pain is not real or that it's 'all in your head'," stressed Wager, noting that changes to neural pathways in the brain can linger long after an injury is gone, reinforced by such associations. "What it means is that if the causes are in the brain, the solutions may be there, too."

Before and after treatment, participants also underwent functional magnetic resonance imaging (fMRI) scans to measure how their brains reacted to a mild pain stimulus.

After treatment, 66% of patients in the treatment group were pain-free or nearly pain-free compared to 20% of the placebo group and 10% of the no-treatment group.

"The magnitude and durability of pain reductions we saw are very rarely observed in chronic pain treatment trials," Ashar said, noting that opioids have yielded only moderate and short-term relief in many trials.

And when people in the PRT group were exposed to pain in the scanner post-treatment, brain regions associated with pain processing -- including the anterior insula and anterior midcingulate -- had quieted significantly.

The authors stress that the treatment is not intended for "secondary pain" -- that rooted in acute injury or disease.

The study focused specifically on PRT for chronic back pain, so future, larger studies are needed to determine if it would yeild similar results for other types of chronic pain.

Meanwhile, other similar brain-centered techniques are already emerging among physical therapists and other clinicians who treat pain.

"This study suggests a fundamentally new way to think about both the causes of chronic back pain for many people and the tools that are available to treat that pain," said co-author Sona Dimidjian, professor of psychology and neuroscience and director of the Renee Crown Wellness Institute at CU Boulder. " It provides a potentially powerful option for people who want to live free or nearly free of pain."

Source: ScienceDaily

Breakthrough tool to show how much exoskeletons reduce back injury risk

 A study led by researchers from Vanderbilt University's Center for Rehabilitation Engineering and Assistive Technology reveals a breakthrough tool to assess the effect of exoskeletons on injury risk.

The tool, called Exo-LiFFT, is an interactive calculator that will help companies looking for ways to overcome workforces struggling with musculoskeletal injuries, missed work, and accelerated retirement amongst skilled laborers.

The study's lead author, Karl Zelik, associate professor of mechanical engineering, said this is a major leap forward to help bring relief to overburdened workers.

The study was published online this month in the Journal of Applied Ergonomics, and projected that exoskeletons have the potential to reduce workplace back injuries in material handling by 20% to 60%. This is a critical advancement because work-related injuries to overburdened workers are a major factor contributing to the current dynamics in the labor market.

"If we can identify the right places to deploy exoskeletons, then they can reduce injury risks as well as bodily discomfort, which impacts workers on the job and at home. Exoskeletons may also help improve worker recruitment and retention, which have been costly pain points for employers amidst the labor shortage," said Zelik, who also is the Chief Scientific Officer at Nashville-based workforce wearable company HeroWear.

Zelik and Ph.D. student Cameron Nurse represented Vanderbilt on the six-person research team, which also featured industrial engineers from Auburn University and an ergonomist from HeroWear. Auburn previously developed foundational ergonomic risk assessment tools, while Vanderbilt and HeroWear have been deeply involved in exoskeleton research, design and translation, as well as the development of industry exoskeleton standards with members of the ASTM International standards committee, which includes companies like Boeing.

"We've been exploring exoskeletons at Boeing for the last few years, with encouraging results to date," said Christopher Reid, Associate Technical Fellow of Human Factors and Ergonomics at Boeing. "It's incredibly important and encouraging to see academia and industry coming together to develop practical risk assessment tools that can help identify and leverage the benefits of emerging safety technologies like exoskeletons."

Overexertion is a primary source of lower back pain and injury, which accounts for 38.5% of work-related musculoskeletal disorders, according to the U.S. Bureau of Labor Statistics. Exoskeletons are now being used daily in factories, warehouses, construction sites, and other workplaces around the world to relieve physical strain on overburdened workers.

"At Toyota, we have relied heavily on new ergonomic assessment tools to support our teams in identifying processes on our manufacturing lines that would benefit from shoulder exoskeletons being deployed as personal protective equipment," said Aaron Sparks, safety project engineer at Toyota North America. "As we begin to investigate and deploy back exoskeletons, it's incredibly exciting, and a major relief, to see similar tools being developed to support with the identification and deployment."

Exo-LiFFT empowers safety professionals and researchers to quickly and easily assess the effect of exoskeletons on back injury risk without the need for costly and time-consuming experiments. This reduces biomechanical assessment time for back exoskeletons from months down to minutes, and provides an evidence-based way to estimate injury risk reduction.

"We have over one hundred facilities across the country where workers are lifting and moving products," said David Brodie, ergonomist lead at Cargill. "New assessment tools like Exo-LiFFT will help us identify where the best opportunities are in our operations to support workers."

Source: ScienceDaily

Can a dangerous microbe offer a new way to silence pain?

 Anthrax has a scary reputation. Widely known to cause serious lung infections in humans and unsightly, albeit painless, skin lesions in livestock and people, the anthrax bacterium has even been used as a weapon of terror.

Now the findings of a new study suggest the dreaded microbe also has unexpected beneficial potential -- one of its toxins can silence multiple types of pain in animals.

The research reveals that this specific anthrax toxin works to alter signaling in pain-sensing neurons and, when delivered in a targeted manner into neurons of the central and peripheral nervous system, can offer relief to animals in distress.

The work, led by investigators at Harvard Medical School in collaboration with industry scientists and researchers from other institutions, is published Dec. 20 in Nature Neuroscience.

Furthermore, the team combined parts of the anthrax toxin with different types of molecular cargo and delivered it into pain-sensing neurons. The technique can be used to design novel precision-targeted pain treatments that act on pain receptors but without the widespread systemic effects of current pain-relief drugs, such as opioids.

"This molecular platform of using a bacterial toxin to deliver substances into neurons and modulate their function represents a new way to target pain-mediating neurons," said study senior investigator Isaac Chiu, associate professor of immunology in the Blavatnik Institute at Harvard Medical School.

The need to expand the current therapeutic arsenal for pain management remains acute, the researchers said. Opioids remain the most effective pain medication, but they have dangerous side effects -- most notably their ability to rewire the brain's reward system, which makes them highly addictive, and their propensity to suppress breathing, which can be fatal.

"There's still a great clinical need for developing non-opioid pain therapies that are not addictive but that are effective in silencing pain," said study first author Nicole Yang, HMS research fellow in immunology in the Chiu Lab. "Our experiments show that one strategy, at least experimentally, could be to specifically target pain neurons using this bacterial toxin."

The researchers caution, however, that for now, this approach remains purely experimental and still needs to be tested and further fine-tuned in more animal studies and, eventually, in humans.

Primed to connect

Researchers in the Chiu lab have long been interested in the interplay between microbes and the nervous and immune systems. Past work led by Chiu has demonstrated that other disease-causing bacteria can also interact with neurons and alter their signaling to amplify pain. Yet only a handful of studies so far have looked at whether certain microbes could minimize or block pain. This is what Chiu and Yang set out to do.

For the current study, they started out by trying to determine how pain-sensing neurons may be different from other neurons in the human body. To do so, they first turned to gene-expression data. One of the things that caught their attention: Pain fibers had receptors for anthrax toxins, whereas other types of neurons did not. In other words, the pain fibers were structurally primed to interact with the anthrax bacterium. They wondered why.

The newly published research sheds light on that very question.

The findings demonstrate that pain silencing occurs when sensory neurons of dorsal root ganglia, nerves that relay pain signals to the spinal cord, connect with two specific proteins made by the anthrax bacterium itself. Experiments revealed that this occurs when one of the bacterial proteins, protective antigen (PA), binds to the nerve cell receptors it forms a pore that serves as a gateway for two others bacterial proteins, edema factor (EF) and lethal factor (LF), to be ferried into the nerve cell. The research further demonstrated PA and EF together, collectively known as edema toxin, alter the signaling inside nerve cells -- in effect silencing pain.

Using the quirks of microbial evolution for new therapies

In a series of experiments, the researchers found that the anthrax toxin altered signaling in human nerve cells in dishes, and it also did so in living animals.

Injecting the toxin into the lower spines of mice produced potent pain-blocking effects, preventing the animals from sensing high-temperature and mechanical stimulations. Importantly, the animals' other vital signs such as heart rate, body temperature, and motor coordination were not affected -- an observation that underscored that this technique was highly selective and precise in targeting pain fibers and blocking pain without widespread systemic effects.

Furthermore, injecting mice with the anthrax toxin alleviated symptoms of two other types of pain: pain caused by inflammation and pain caused by nerve cell damage, often seen in the aftermath of traumatic injury and certain viral infections such as herpes zoster, or shingles, or as a complication of diabetes and cancer treatment.

Additionally, the researchers observed that as the pain diminished, the treated nerve cells remained physiologically intact -- a finding that indicates the pain-blocking effects were not due to injury of the nerve cells but rather stemmed from the altered signaling inside them.

In a final step, the team designed a carrier vehicle from anthrax proteins and used it to deliver other pain-blocking substances into nerve cells. One of these substances was botulinum toxin, yet another potentially lethal bacterium known for its ability to alter nerve signaling. That approach, too, blocked pain in mice. The experiments demonstrate this could be a novel delivery system for targeting pain.

"We took parts of the anthrax toxin and fused them to the protein cargo that we wanted it to deliver," Yang said. "In the future, one could think of different kinds of proteins to deliver targeted treatments."

The scientists caution that as the work progresses, the safety of the toxin treatment must be monitored carefully, especially given that the anthrax protein has been implicated in disrupting the integrity of the blood-brain barrier during infection.

The new findings raise another interesting question: Evolutionarily speaking, why would a microbe silence pain?

Chiu thinks that one explanation -- a highly speculative one, he added -- may be that microbes have developed ways to interact with their host in order to facilitate their own spread and survival. In the case of anthrax, that adaptive mechanism may be through altered signaling that blocks the host's ability to sense pain and therefore the microbe's presence. This hypothesis could help explain why the black skin lesions that the anthrax bacterium sometimes forms are notably painless, Chiu added.

Source: ScienceDaily

Scientists discover a new type of heart cell

 Disturbances in a newly discovered type of heart cell may underlie certain congenital heart abnormalities and a broader array of autonomic nervous system conditions.

• The cells, called cardiac nexus glia, were shown to play an important role in both heart rate and heart rhythm.
• Previously, scientists believed that nexus glia only occurred in the central nervous system.

Glial cells are present throughout the nervous system and are critical for normal development and function.

Experts categorize these cells according to their primary function in the nervous system. Subtypes include ensheathing glia, microglia, and astroglia.

The nervous system comprises the central nervous system (CNS), the peripheral nervous system (PNS), and the autonomic nervous system (ANS). The latter two work together to control nonbrain organ systems and functions, including muscle movement, digestion, “fight-or-flight” responses, breathing, circulation, and heart rate.

Now, researchers have discovered a new type of glial cell in the heart that is crucial for both development and function and may explain certain congenital abnormalities and other cardiac diseases.

Researcher Cody Smith, Ph.D., associate professor in the Department of Biological Sciences at the University of Notre Dame, IN, and colleagues reported their findings in PLOS Biology. They also outline its function and location.

Utilizing tissue from zebrafish, mice, and humans, Dr. Smith pinpointed a region of the heart called the outflow tract (OT) that harbored cells in his search for astroglial-like cells.

The novel discovery of these cardiac nexus glia was consistent across species. Interestingly, this region of the OT affects heart health.

Developmentally, neuronal cells in the CNS typically precede those in the PNS and ANS, so Dr. Smith and his team sought the origin of these astroglial cell populations before they make their way into the heart. Using the zebrafish model, he confirmed the source of these glial cells was the neural crest located in the hindbrain.

Within 24 hours of fertilization of the zebrafish embryos, the glial cells began migrating into the heart. By day 4, they had populated the OT. There, a portion of the cells then differentiated into cardiac nexus glia while another portion differentiated into cardiomyocytes and smooth muscles cells.

Dr. Smith’s team later confirmed the presence of these astroglia in both mouse and human cardiac tissue. Contrary to previous research, it was the astroglia that preceded neuronal development — this was difficult to explain given that the axonal branching of neurons only occurs in the absence of glia.

Astroglia and heart function

To test their hypothesis that these cardiac nexus glia regulate heart-related autonomic functions, Dr. Smith and his team removed or ablated the cells across species. On average, the ablated samples had increased heart rates of more than 20 beats per minute. This rhythmic increase in heart rate is known as ventricular tachycardia.

Since ventricular tachycardia occurs due to an imbalance of ionic activity in the OT, the scientists wanted to know whether the absence of cardiac nexus glia in this region was the primary cause.

To do this, they ablated cardiac nexus glia in other regions, notably the atrium — the upper chamber of the heart. There was no effect on heart rate, confirming the importance of cardiac nexus glia in the OT region.

Furthermore, they uncovered significant downstream effects of this cardiac nexus glia disruption on the sympathetic and parasympathetic branches of the ANS. Chemical manipulation of cardiac nexus glia caused a major increase in the duration of ventricular fibrillation — an irregular heartbeat — indicating a reactive role of the sympathetic nervous system in dysrhythmia.

Dr. Smith noted that 30% of congenital heart abnormalities have direct ties to OT dysfunction. However, whether this is specifically due to an aberrance of cardiac nexus glia in the developmental process remains unclear.

Source: Medical News Today

Cholesterol research: Does industry funding skew results?

 

• There is much debate about the role of dietary cholesterol in people’s health.
• An increasing number of studies into dietary cholesterol have funding from the food industry.
• A new review identifies an association between studies with food industry funding and more favorable interpretations of the role of egg cholesterol in human health.

In a systematic review, researchers looked at how authors of industry- and non-industry-funded studies interpret the results of research on egg consumption and blood cholesterol levels.

The study, which appears in the American Journal of Lifestyle Medicine, found that the authors behind studies funded by industry were more likely to interpret results regarding the relationship between egg consumption and cholesterol favorably — and often not in line with what the data suggested.

Cholesterol controversy

In the past, scientists have recommended that people consume under 300 milligrams (mg) of cholesterol each day to maintain good cardiovascular health.

However, more recent research has not found a significant relationship between dietary cholesterol and the risk of cardiovascular disease.

As a consequence, recent guidelines from the American Heart Association (AHA) and the American College of Cardiology have not specified a target for daily dietary cholesterol intake.

Nonetheless, there has been “intense debate” regarding the role that consuming eggs might play in increasing blood cholesterol levels. On the one hand, eggs are a major source of dietary cholesterol. On the other, they are a cheap, nutritious, and widely available food item.

Systematic review

In the recent study, the researchers wanted to understand how funding sources for research into egg consumption and blood cholesterol levels have changed over time.

They also wanted to know whether or not the source of funding for studies — that is, either industry or non-industry — made a difference in how researchers interpreted the results.

The researchers searched databases for articles involving adults that studied egg or egg yolk consumption and total or low-density lipoprotein cholesterol.

They identified 211 studies published between 1950 and 2019 that met these inclusion criteria.

Misinterpretation?

The researchers found that industry-funded research into egg consumption and cholesterol increased from 0% of cholesterol studies in the 1950s to 60% of these studies in the 2010s.

The majority of the studies found that egg consumption did increase blood cholesterol concentrations.

However, the authors of the review found that 49% of the studies funded by industry did not accurately interpret their findings, being more likely to suggest a neutral or positive relationship between egg consumption and blood cholesterol concentrations. This compares with 13% of the studies not funded by industry.

Medical News Today spoke with corresponding study author Dr. Neal Barnard, an adjunct professor of medicine at the George Washington University School of Medicine. Dr. Barnard is also the president of the Physicians Committee for Responsible Medicine (PCRM).

He said: “The egg industry has a huge financial interest in making eggs seem healthy. So, industry-funded researchers have tried to downplay eggs’ cholesterol-raising effect. They have not really succeeded, though: Even their own studies show that eggs raise cholesterol.”

Dr. Barnard said that industry funding was not necessarily the problem — rather, the problem is when pressures from industry result in interpretations that do not reflect the findings.

Source: Medical News Today