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The study was conducted by researchers from Tel Aviv University’s Sackler Faculty of Medicine, led by Prof. Shai Efrati, MD, from the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center, and Prof. Jacob Ablin, MD, from the Tel Aviv Sourasky Medical Center. The results of the study were published in the journal PLOS One.  

"At the end of the treatment, two out of five patients in the hyperbaric treatment group showed such a significant improvement that they no longer met the criteria for fibromyalgia. In the drug treatment group, this did not happen to any patient." Prof. Shai Efrati

"Fibromyalgia is a chronic pain syndrome, from which between 2% - 8% of the population suffers," explains Prof. Shai Efrati. "Until 15-20 years ago, there were doctors who believed that it was a psychosomatic illness and recommended that patients with chronic pain seek mental health care. Today we know that it is a biological illness, which damages the brain's processing of the signals received from the body. When this processing is malfunctioning, you feel pain without any real damage in related locations."

"Fibromyalgia can be induced by variable triggers - from certain infections, as we have recently seen in post-COVID patients, through post-traumatic stress syndrome to head injuries. We wanted to test whether the new protocols of hyperbaric medicine can provide better results than pharmacological medicine, for patients in whom the fibromyalgia was induced by traumatic brain injury."

Prof. Shai Efrati

Dramatic Results

Hyperbaric medicine is a form of treatment in which the patients stay in special chambers where the pressure is higher than the atmospheric pressure at sea level, and where the patients breathe 100% oxygen. Hyperbaric medicine is considered safe, used in many places including Israel, and is already used to treat a long list of medical conditions.

In recent years, scientific evidence has been accumulating that certain, newly developed, dedicated hyperbaric treatment protocols can lead to the growth of new blood vessels and neurons in the brain.

"Overall, existing treatments are not good enough. [Fibromyalgia] is a chronic disease that significantly affects the quality of life, including young people, and hyperbaric medicine meets an acute need of these patients." Prof. Jacob Ablin

In their current study, the researchers from Tel Aviv University recruited 64 Israelis aged 18 and older who suffered from fibromyalgia as a result of a head injury, and randomly divided them into two groups: one group was exposed to 100% pure oxygen at a pressure of two atmospheres for 90 minutes (with fluctuations in oxygen during the treatment every 20 minutes), five days a week, for three months. The second group received the conventional pharmacological treatment (i.e., the drugs pregabalin, which is known under the trade name "Lyrica", and duloxetine, which is better known as "Cymbalta").

"The results were dramatic," says Prof. Efrati. "At the end of the treatment, two out of five patients in the hyperbaric treatment group showed such a significant improvement that they no longer met the criteria for fibromyalgia. In the drug treatment group, this did not happen to any patient. Furthermore, the average improvement in the pain threshold tests was 12 times better in the hyperbaric group compared to the medication group. And in terms of quality-of-life indicators, as reported by the patients, we saw significant improvements in all the indicators among the patients who received hyperbaric treatment."

Meets Acute Need

"Today's accepted treatment for fibromyalgia includes pharmacologic and non-pharmacologic components," says Prof. Ablin. "with respect to the pharmacologic approach, these drugs are not very effective and therefore the emphasis is on the non-pharmacological side, that is, on external correction of pain processing within the nervous system. Currently used recommendations includes aerobic activity, hydrotherapy, cognitive-behavioral therapy and movement-based therapies such as Tai Chi. In addition, quite a few patients request treatment with medical cannabis, and for some it helps."

"In the group that received hyperbaric treatment, you could see the repair of the brain tissue, while in the control group there was only an attempt to relieve the pain - without treating the damaged tissue - and of course the medication group experienced the side effects associated with drug treatment." Prof. Shai Efrati

"Overall, existing treatments are not good enough. [Fibromyalgia] is a chronic disease that significantly affects the quality of life, including young people, and hyperbaric medicine meets an acute need of these patients. Of course, these are preliminary studies, and we must follow and see what effect the medical protocol has on the patients after one, two and three years - and if it is necessary to maintain the positive results with further exposure to hyperbaric sessions."

Looking to Cure

According to Prof. Efrati, the importance of the research is in healing the damaged brain tissue - and not in treating its superficial symptoms: "In the group that received hyperbaric treatment, you could see the repair of the brain tissue, while in the control group there was only an attempt to relieve the pain - without treating the damaged tissue - and of course the medication group experienced the side effects associated with drug treatment. This is a difference in approach: to cure instead of just treating the symptoms."

"We assessed the improvement of the participants in the hyperbaric group more than a week after the last hyperbaric session. More follow-up studies are needed to see the duration of the beneficial effect of the treatment and if and for whom additional treatment will be needed. Our goal as doctors is not only to treat the symptoms but, to the extent possible, also to treat the source of the problem, thus improving the quality of life of fibromyalgia patients."

"It is important to emphasize that the dedicated hyperbaric oxygen treatment protocol found to be effective is only available in medical centers that have licensed hyperbaric chambers. Be careful of so-called 'private chambers', since these cannot provide the therapeutic protocol found to be effective, and they are not regulated or approved for medical use," cautions Prof. Efrati.

The model describes a phenomenon which the team of researchers refer to as "border induced selection," and was developed under the leadership of PhD student Gil Loewenthal in the laboratory of Prof. Tal Pupko from the Shmunis School of Biomedicine and Cancer Research at the The George S. Wise Faculty of Life Sciences and in collaboration with Prof. Itay Mayrose, also from TAU's Faculty of Life Sciences. The study was published in the journal Open Biology.

Throughout evolution, the size of the genome in living creatures in nature changes. For example, some salamander species have a genome ten times larger than the human genome. "The rate of deletions and short insertions, dubbed 'indels', is usually measured by examining pseudogenes," explains Prof. Pupko. "Pseudogenes are genes that have lost their function, and in which there are frequent mutations, including deletions and insertions of DNA segments."

In previous studies that characterized the indels, it was found that the rate of deletions is greater than the rate of additions in a variety of creatures including bacteria, insects, and even mammals such as humans.

Prof. Tal Pupko

Reverse Bias for Short Segments

The question the researchers sought to answer is how the genomes are not deleted when the probability of DNA deletion events is significantly greater than DNA addition events: "We have provided a different view to the dynamics of evolution at the DNA level," says Loewenthal. "When measuring the rate of indels there will be more deletions, but the measurements are carried out in pseudogenes which are quite long sequences. We assert that in shorter neutral segments, deletions would likely remove adjacent functional segments which are essential for the functioning of the organism, and they will therefore be rejected [through 'border-induced selection']. Accordingly, we assert that when the segment is short, there will be a reverse bias – there will be more insertions than deletions - and therefore short neutral segments are usually retained."

"In our study, we simulated the dynamics of indels, while taking into account the effect of 'border-induced selection,' and compared the simulation results to the distribution of human intron lengths (introns are DNA segments in the middle of a protein-coding gene, which themselves do not code for a protein). A good match was obtained between the results of the simulations and the distribution of lengths observed in nature, and we were able to explain peculiar phenomena in the length distribution of introns, such as the large variation in intron lengths, as well as the complex shape of the distribution which does not look like a standard bell curve."

The study was conducted by Prof. Shai Meiri of TAU's School of Zoology, The George S. Wise Faculty of Life Sciences, and of The Steinhardt Museum of Natural History Museum, as well as researchers from Finland, the USA, Belgium, Madagascar, Hong Kong, and Israel. The paper was published in Molecular Phylogenetics and Evolution.

"Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes," explains Prof Meiri.

"For years, they were considered members of the largest snake family, the Colubridae, but multiple DNA tests conducted over the last decade contradicted this classification. Since then, snake researchers around the world have tried to discover which family these snakes belong to – to no avail. In this study we joined the scientific effort."

The researchers used micro-CT technology – high-resolution magnetic imaging, to examine the snake's morphology, focusing specifically on the skull. In addition, they applied methods of deep genomic sequencing – examining about 4,500 ultra-conserved elements, namely regions in the genome that take millions of years to exhibit any change.

Prof. Meiri explains that "in addition to the DNA of Micrelaps, we sampled DNA from various snake groups to which they might have belonged. This way, we discovered some unique genomic elements in Micrelaps, which were not found in any of the other groups."

Prof. Shai Meiri

"Even through these snakes have been known for decades, they were mistakenly included in other families for many years." Prof. Shai Meiri

Family Relocation

According to the researchers their findings indicate that Micrelaps diverged from the rest of the evolutionary tree of snakes about 50 million years ago. Since then, these snakes have evolved independently, as a distinct and separate family.

Apparently, this is a very small family, including only three species: two in Kenya and Tanzania in East Africa, and one in Israel and nearby regions (northern Jordan and the Palestinian Authority, southern Syria, and southern Lebanon). The geographic dispersion suggests that these snakes probably originated in Africa, and then, at some point in their history, some of them made their way north through the Great Rift Valley.

"In this study we were able to associate a new snake family – the Micrelapidae. Even through these snakes have been known for decades, they were mistakenly included in other families for many years. Since most animals have already been classified into well-defined families, such a discovery of a new family is quite a rare occurrence in modern science," concludes Prof. Meiri.