“Promising evidence” that osteopathy may relieve musculoskeletal pain

New App Designed to help hairdressers Tackle Musculoskeletal Disorders

There’s “promising evidence” that osteopathy, the physical manipulation of the body’s tissues and bones, may relieve the pain associated with musculoskeletal conditions, finds a review of the available clinical evidence, published in the open access journal BMJ Open.

But there’s little or only inconclusive evidence to back its use in children, and for the treatment of migraine or irritable bowel syndrome (IBS), the findings show.

Osteopathy, which was first developed in the late 1800s in the USA, is based on the principle that the structure (anatomy) and function (physiology) of a person’s body are intertwined. It aims to repair imbalances in this relationship.

In common with other forms of complementary medicine, osteopathy has grown in popularity over the past decade, particularly for the treatment of musculoskeletal disorders. The researchers therefore wanted to assess its safety and effectiveness for different conditions. 

They trawled research databases for systematic reviews and pooled data analyses (meta analyses) of relevant randomised controlled clinical trials, published up to November 2021. 

Only trials carried out by doctors with osteopathic training or osteopaths were included.

The search uncovered nine systematic reviews or meta analyses conducted between 2013 and 2020, involving 55 primary trials and 3740 participants. 

The systematic reviews reported on the use of osteopathy in a wide range of conditions, including acute and chronic non-specific low back pain, chronic non-specific neck pain, chronic non-cancer pain, primary headache, and IBS.

The pooled data analyses reported that osteopathy is more effective than other approaches in reducing pain and improving physical function in acute/chronic non-specific lower back and neck pain and in chronic pain not associated with cancer. 

The other comparative approaches included dummy treatment (placebo), sham osteopathy, light touch therapy, no treatment, waiting list, conventional treatment, physiotherapy or other forms of complementary medicine.

But small sample size, contradictory findings, and wide variations in study design meant that the evidence on the effectiveness of osteopathy for use in children with various conditions, ranging from attention deficit hyperactivity disorder to asthma and infantile colic, and the treatment of migraine and IBS, was limited or inconclusive.

No serious side effects associated with the therapy were reported in the 7 systematic reviews that evaluated them, although only two defined how these were measured.

“This overview suggests that [osteopathy] could be effective in the management of musculoskeletal disorders, specifically with regard to [chronic non-specific low back pain] and [low back pain ] in pregnant women or [those who have just had a baby],” write the researchers. 

“In contrast, inconclusive evidence was derived from [systematic reviews] analysing osteopathy efficacy on paediatric conditions, primary headache, and IBS,” they add. 

“Nevertheless, based on the low number of studies, some of which are of moderate quality, our overview highlights the need to perform further well-conducted [systematic reviews] as well as clinical trials (which have to follow the specific guidelines for non-pharmacological treatments) to confirm and extend the possible use of [osteopathy] in some conditions as well as its safety,” they conclude.

Vegan diet eases arthritis pain, finds new study

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A low-fat vegan diet, without calorie restrictions, improves joint pain in patients with rheumatoid arthritis, according to a new study conducted by researchers at the Physicians Committee for Responsible Medicine and published in the American Journal of Lifestyle Medicine. Study participants also experienced weight loss and improved cholesterol levels.

“A plant-based diet could be the prescription to alleviate joint pain for millions of people suffering from rheumatoid arthritis,” says Neal Barnard, MD, lead author of the study and president of the Physicians Committee. “And all of the side effects, including weight loss and lower cholesterol, are only beneficial.”

Rheumatoid arthritis is a common autoimmune disease that typically causes joint pain, swelling, and eventually permanent joint damage.

At the outset of the Physicians Committee’s study, participants were asked to use a visual analog scale (VAS) to rate the severity of their worst joint pain in the preceding two weeks, from “no pain” to “pain as bad as it could possibly be.” Each participant’s Disease Activity Score-28 (DAS28) was also calculated based on tender joints, swollen joints, and C-reactive protein values, which indicate inflammation in the body. DAS28 increases with rheumatoid arthritis severity.

During the study, 44 adults previously diagnosed with rheumatoid arthritis were assigned to one of two groups for 16 weeks. The first group followed a vegan diet for four weeks, with the elimination of additional foods for three weeks, then reintroduction of the eliminated foods individually over nine weeks. No meals were provided, and participants handled their own food preparation and purchases, with guidance from the research team. The second group followed an unrestricted diet but were asked to take a daily placebo capsule, which had no effect in the study. Then the groups switched diets for 16 weeks.

During the vegan phase of the study, DAS28 decreased 2 points on average, indicating a greater reduction in joint pain, compared to a decrease of 0.3 points in the placebo phase. The average number of swollen joints decreased from 7.0 to 3.3 in the vegan phase, while that number actually increased from 4.7 to 5 in the placebo phase. For those who completed the study, VAS ratings also improved significantly in the vegan phase, compared with the placebo phase.

The vegan diet also led to greater decreases in DAS28 in a subanalysis that excluded individuals who increased medications during the study and another subanalysis limited to participants making no medication changes.

In addition to reductions in pain and swelling, body weight decreased by about 14 pounds on average on the vegan diet, compared with a gain of about 2 pounds on the placebo diet. There were also greater reductions in total, LDL, and HDL cholesterol during the vegan phase.

Chronic low back pain linked to atrophy in pain-related brain regions


Chronic low back pain linked to atrophy in pain-related brain regions

 Chronic low back pain (CLBP) is associated with reductions in brain volume in areas involved in pain processing, reports a study in PAIN®the official publication of the International Association for the Study of Pain (IASP)The journal ispublished in the Lippincott portfolio by Wolters Kluwer.

“These findings suggest that CLBP is related to lower brain volumes of pain-related regions not only in clinical patients with severe pain but also in the general population,” according to the report by Mao Shibata, MD, PhD, and colleagues of Kyushu University, Fukuoka, Japan.

Brain atrophy in pain-related regions seems specific to CLBPAs part of an ongoing Japanese study of disease risk factors (the Hisayama Study), the researchers analyzed brain magnetic resonance imaging (MRI) scans from 1,106 participants aged 65 years or older. On a study questionnaire, 17.1% of participants reported having CLBP, defined as low back pain present for 3 months or longer.

The remaining participants reported no chronic pain or chronic pain in areas other than the low back. Older adults with CLBP had lower education levels, higher rates of high blood pressure and depression symptoms, and lower rates of regular exercise.

In analyzing the MRI scans, the researchers focused on 10 brain areas with evidence of involvement in pain processing. The presence of CLBP was linked to reduced brain volume (atrophy) in 4 of the 10 areas – the ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate cortex, and amygdala – compared to participants with no chronic pain. In addition, a “significant cluster” (the left superior frontal gyrus) with reduced brain volume  was identified in a relatively large sample size by using the QDEC (the Query, Design, Estimate, Contrast interface) approach, a method that did not prespecify brain region of interest.

The patterns remained significant after adjustment for a wide range of sociodemographic, health, and lifestyle factors. For older adults with chronic pain in other areas, regional brain volumes in pain-related areas were no different compared to subjects with no chronic pain.

Among participants with CLBP, those with more severe pain had lower brain volumes in pain-related areas, suggesting a “dose-response” effect. Some of the affected areas differed by age group – ie, participants aged 65 to 74 years versus those aged 75 years or older.

Chronic low back pain is a very common problem and the leading cause of years lived with disability. Yet approximately 90% of patients with CLBP cannot identify any clear specific cause or origin of their pain. A growing body of evidence suggests that CLBP is associated with lower brain volumes in pain-related brain areas.

The new study adds new evidence of atrophy in pain-related brain areas in a large population-based sample, with varying degrees of CLBP severity or other types of chronic pain. The researchers emphasize that the study participants had not necessarily sought any treatment for CLBP. That’s a new finding, as most previous studies have focused on patients receiving care for severe chronic pain.

The researchers acknowledge some key limitations of their study: it cannot show any cause-and-effect relationship and cannot account for unmeasured factors, such as pain medication use, that might affect brain volumes. Dr. Shibata and colleagues conclude, “Further investigations are needed to clarify the mechanism underlying the association between CLBP and regional brain atrophy.”

Tablet containing CBD shows promise in reducing pain

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CBD and pain


An orally absorbed tablet containing cannabidiol (CBD) effectively reduces pain after shoulder surgery with no safety concerns, a new study finds.   

Led by researchers in the Department of Orthopedic Surgery at NYU Langone Health, the study found that the tablet ORAVEXXTM safely managed pain after minimally invasive rotator cuff surgery, and did not produce side effects sometimes associated with CBD use, such as nausea, anxiety, and liver toxicity. The findings were presented at the American Academy of Orthopaedic Surgeon’s (AAOS) 2022 Annual Meeting in Chicago.

“There is an urgent need for viable alternatives for pain management, and our study presents this form of CBD as a promising tool after arthroscopic rotator cuff repair,” says lead investigator Michael J. Alaia, MD, associate professor in the Department of Orthopedic Surgery at NYU Langone Health. “It could be a new, inexpensive approach for delivering pain relief, and without the side effects of anti-inflammatory drugs like NSAIDs and addiction risks linked to opiates. Additionally, CBD has the benefit of pain relief without the psychotropic effects associated with THC or marijuana.”

The multicenter Phase 1/2 clinical trial randomly sorted 99 participants across two study sites (NYU Langone Health and Baptist Health/Jacksonville Orthopaedic Institute) between the ages of 18 and 75 into a placebo group and a group receiving oral-absorbed CBD. Participants were prescribed a low dose of Percocet, instructed to wean off the narcotic as soon as possible, and to take the placebo/CBD three times a day for 14 days after the surgery.  

On the first day after surgery, patients receiving CBD experienced on average 23 percent less pain as measured by the Visual Analog Scale (VAS) pain score compared to patients receiving the placebo, highlighting that in patients with moderate pain, CBD may render a significant benefit. On both the first and second days after surgery, patients receiving CBD reported 22 to 25 percent greater satisfaction with pain control compared to those receiving placebo. Further analysis also showed that patients receiving 50 mg of CBD reported lower pain and higher satisfaction with pain control compared to patients receiving placebo. No major side effects were reported.

While the results are promising, Dr. Alaia cautioned consumers against seeking out commercialized CBD products. “Our study is examining a well-designed, carefully scrutinized product under an investigational new drug application sanctioned by the FDA. This is currently still experimental medicine and is not yet available for prescription,” he added.

ORAVEXX™, the buccally absorbed tablet used in this study, is designed and manufactured by Orcosa Inc., a life sciences company. It is a non-addictive, fast-absorbing CBD composition designed to treat pain.

Moving forward, NYU Langone Health has launched a second study looking at whether ORAVEXX™ can specifically treat chronic pain in patients with osteoarthritis. Multiple Phase 2 studies also are planned to evaluate the drug’s efficacy for other acute and chronic pain management issues and assess the role of CBD on inflammation.

New potentially painkilling compound found in deep-water cone snails

New potentially painkilling compound found in | EurekAlert!


Scientists already know that the venom of cone snails, which prowl the ocean floor for a fish dinner, contains compounds that can be adapted as pharmaceuticals to treat chronic pain, diabetes and other human maladies. But the cone snails’ venom has more secrets yet to be revealed. In a new study published in Science Advances, researchers report that a group of cone snails produces a venom compound similar to the hormone somatostatin.

While they continue to learn more about this venom compound and its possible pharmaceutical applications, the results show the wide variety of drug leads that venomous animals produce,  designed and refined over millions of years.

“We have to broaden the scope of what we expect that these venomous animals make, assuming that they could really be making anything,” says Helena Safavi-Hemami, an adjunct assistant professor at the University of Utah and associate professor at the University of Copenhagen.  “We should look very broadly and keep an open eye for completely new compounds.”

“Cone snail venom is like a natural library of compounds,” adds Iris Bea Ramiro of the University of Copenhagen. “It is just a matter of finding what is in that library.”

Find the full study here. This research was funded by the U.S. Department of Defense, a Villum Young Investigator Grant, the Department of Science and Technology—Philippine Council for Health Research and Development, USAID and the Benning Society.

Beginning in Bohol

The story begins in the Philippines, on the island of Bohol where Ramiro grew up. Although she and most Boholanos didn’t encounter cone snails often except for finding shells on the beach, fishermen knew how to find and catch the venomous snails, which are often sold to shell collectors and are sometimes eaten. One fisherman told Ramiro that his parents warned him to avoid eating a bean-like organ in the snail.

“The bean-like structure is actually a bulb that is connected to the gland where venom is produced,” Ramiro says.

Some cone snails are fish hunters. Some of those use a “taser-and-tether” hunting strategy, shooting a barbed hook into a fish and delivering a jolt of venom that chemically electrocutes and paralyzes the fish. Others use a net hunting strategy, releasing a cloud of venom into the water with compounds that leave the fish sensory-deprived and disoriented.

Of the estimated eight groups of fish hunting cone snails, though, only half have been extensively studied. Among the least-studied lineages are the Asprella cone snails. They’re not shallow-water snails, like some others. They like deeper waters, at depths of 200-800 feet (60-250 m), and have been less accessible to scientists.

As a graduate student at the University of the Philippines, Ramiro began studying Conus rolani, a species of Asprella snail. “No one in our lab was working on it at that time,” she says. “I was just looking to identify any small peptide (chain of amino acids) from the venom of C. rolani that had unusual or interesting activity in mice.”

She found one. A small peptide from the venom caused mice to act sluggishly or unresponsive. But it was slow-acting, hardly the expected effect since other cone snails produced venoms that acted almost immediately. It had a few similarities to the hormone somatostatin (more on that later) but not enough to say conclusively that the venom peptide and the human hormone were functionally related.

While exploring how and why the venom worked, Ramiro made a visit to the University of Utah, a hub of cone snail research.

Cone snails at the U

Far from the glittering waters of the Pacific, U researchers have been studying cone snails and their venom since 1970, when Baldomero “Toto” Olivera arrived in Salt Lake City, bringing the cone snail research he’d begun in his native Philippines.

Decades of study have provided an abundance of information about how venom compounds interact with the bodies of prey fish, including how the venoms interact with receptors in the body and overwhelm natural biochemical processes. Olivera and his colleagues investigated whether those effects could be employed as pharmaceuticals in humans. One effort yielded a pain medication, Prialt. Another, in which Safavi played a leading role at the U as an assistant professor, investigated how insulin analogs produced by cone snails might be adapted as a fast-acting insulin for people with diabetes.

“Somehow cone snails take some of their hormones and turn them into weapons,” Safavi says. So she and other researchers helped Ramiro compare the peptide she’d found, now called Consomatin Ro1, to known human proteins.

Frank Whitby, a research associate professor in the Department of Biochemistry, used X-ray crystallography to determine the structure of Consomatin Ro1. “This was an important contribution because it showed that Consomatin Ro1 does not resemble somatostatin but rather resembles a drug analog of somatostatin called octreotide,” says Christopher Hill, distinguished professor of biochemistry.

Meanwhile the research team also worked with local fishermen off Cebu, an island near Bohol, to bring Asprella specimens to the lab to observe their behavior and learn more about their biochemistry.

It took a year, Ramiro says, to confirm that the peptide that she’d originally isolated from the C. rolanisnail activates two of the five human receptors for somatostatin “with unique selectivity,” she says.

“Then,” Safavi says, “we really wanted to understand what it’s doing and how it could be better than somatostatin.”

Snails and snakes 

Somatostatin is a hormone that, in humans and many other vertebrates, is generally an inhibitor—kind of a wet blanket. It’s the main inhibitor of growth hormone, and can be used to treat the excessive growth disorder acromegaly. It also inhibits hormones in the pancreas and signals of pain and inflammation.

“So it’s this hormone that has many, many different functions in the human body,” Safavi says, “But it’s always blocking something. And because of that, it had been an interesting hormone for drug development for some time.”

How can a hormone like somatostatin work as a weaponized venom, especially when it acts slowly? The best way to understand that, the researchers say, is to look to another predator with a slow-acting venom: the rattlesnake.

Rattlesnakes, vipers and cobras have developed a hunting strategy to protect themselves against dangerous prey that could possibly fight back. The snakes strike, injecting their venom, and then retreat. They then wait and follow their prey until the venom takes its full effect and the prey is dead or nearly dead and safe to approach and eat.

Observations of cone snails in tanks showed similarities to the rattlesnakes’ strike-and-release hunting strategy. After injecting venom, the snails would wait, sometimes up to three hours, before delivering a second injection and waiting again.

“And only when the prey is really incapacitated and unable to swim, they come and eat it,” Safavi says. “If you don’t catch the prey immediately, you have the advantage of just waiting until the prey can no longer move. That’s particularly important if the prey can fight back.”

How does a venom component that mimics somatostatin help with that strategy? It’s still unclear. The study showed that Consomatin Ro1 can block pain in mice with efficiency similar to morphine, and it may be used to block pain so that prey doesn’t know it’s been struck, Safavi says. Different species of fish hunters may use these toxins for different purposes.

Tiny drug designers

As a somatostatin analog, Safavi says, Consomatin Ro1 is structured “as if it was designed by drug makers.” The molecule is short, stable and efficient in the receptors it targets.

That’s likely a reflection of the process of evolution. Cone snails likely began using their own somatostatin in venom and then, through generations of trial and error, refined the compound for maximum effectiveness. That’s an advantage for us, since the biology of fish and humans is similar enough that a compound that’s highly effective in fish will likely be effective in humans.

It’s yet to be seen whether Consomatin Ro1 is more effective than somatostatin analog drugs already on the market that treat growth disorders or tumors.

“The advantage with the cone snails, though, is that there are so many species,” Safavi says. “And we know that many of these species make somatostatin, so the chances of finding the best analog might be pretty high.”

Future directions

Next, the research team wants to investigate the origin of Consomatin Ro1 in snails, as well as better understand the potential of the compound as an anti-inflammatory or pain reliever. They’ll also look to see if modifications to the compound could make it even more useful.

The results show how venomous animals can turn a hormone into a weapon and suggest that the range of biochemical tools in venom might be broader than previously thought.

“There’s evidence that viruses also turn hormones into weapons,” Safavi says. “We can spend a lot of time trying to design good hormone drugs, or we could try to look at nature more often. And I think if we did the latter, we might be more successful or we might be faster in our drug development efforts.” Safavi will continue this work when she returns to the U as an associate professor of biochemistry in summer 2022.

“This gives insight to the development of next-generation therapeutics,” says Hill. “More generally, this is a great example of how evolution in the natural world has already developed drug-like natural products that have great potential to improve human health.”

“Discovering new peptides from the cone snails is fun and exciting but it could be a long and difficult journey,” Ramiro says, adding that the integration of various disciplines including biology, biochemistry and pharmacology have made this study successful. “There is still so much we can find, discover and learn from the cone snails and their venom.”