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Symbolic picture: acupuncture.
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Cambridge (USA) – In experiments, Harvard neurologists have successfully used acupuncture in the form of electroacupuncture to contain the so-called cytokine storm in mice with systemic inflammation. Acupuncture therefore activated the various signaling pathways that triggered either an inflammatory or an anti-inflammatory reaction in animals with bacterially induced systemic inflammation. According to the authors, the results represent a crucial step in defining the neuroanatomical mechanisms underlying acupuncture and provide a roadmap for using the approach to treat inflammatory diseases.
As the researchers around Qiufu Ma, professor of neurobiology at the Blavatnik Institute at the Harvard Medical School and researchers at the Dana-Farber Cancer Institute are currently in the journal „Neuron“ (DOI: 10.1016/j.neuron.2020.07.015) report, they also found that three factors determine the impact of acupuncture on response: location, intensity, and timing of treatment. Where in the body the stimulation occurred, how strong it was and when the stimulation was administered, led to dramatically different effects on markers of inflammation and the survival of the test animals.
According to the neurologists, the experiments represent a crucial step in defining the neuroanatomical mechanisms underlying acupuncture and provide a roadmap for using the approach to treat inflammatory diseases.
background
The cytokine storm phenomenon has received widespread attention as a complication of severe COVID-19, but this aberrant immune response can occur with any infection and has long been known to doctors as a hallmark of sepsis, an organ-damaging, often fatal inflammatory response to infection. It is estimated that sepsis affects 1.7 million people in the United States and 30 million people worldwide each year.
At the same time, the scientists also point out that before any therapeutic application, the observations would have to be confirmed in further research – both in animals and in humans – and the optimal parameters for acupuncture stimulation would have to be carefully defined.
“Our results are an important step in the ongoing effort to not only understand acupuncture’s neuroanatomy, but also to find ways to integrate it into the treatment arsenal of inflammatory diseases, including sepsis,” said study director Qiufu Ma.
In the study, acupuncture stimulation influenced the animals’ handling of the cytokine storm – the rapid release of large amounts of cytokines, molecules that promote inflammation.
Background: acupuncture
Acupuncture, rooted in traditional Chinese medicine, has recently become more integrated into Western medicine, particularly for the treatment of chronic pain and gastrointestinal disorders. The approach involves the mechanical stimulation of certain points on the body surface – the acupuncture points that run along so-called meridians. The stimulation supposedly triggers nerve signals and remotely influences the function of the internal organs that correspond to or are assigned to certain acupuncture points. However, the basic mechanisms that underlie the effects and effects of acupuncture are not yet fully understood. The Harvard neurologists see the new study as an important step in mapping the neuroanatomy of acupuncture.
As a neurobiologist who studies the basic mechanisms of pain, Ma has been researching the biology of acupuncture for years. Intrigued by a 2014 article that showed that the use of acupuncture in mice can reduce systemic inflammation by stimulating the vagal-adrenal axis – a signaling pathway through which the vagus nerve transmits signals to the adrenal glands – to the Trigger glands to release dopamine. Ma’s curiosity was further heightened by the work published in 2016 showing that vagus nerve stimulation tamed the activity of inflammatory molecules and reduced symptoms of rheumatoid arthritis.
In the current study, researchers used electro-acupuncture – a modern take on the traditional manual approach, which involves inserting ultra-thin needles just under the skin into different areas of the body. In electroacupuncture, very thin electrodes are used instead of needles, which are inserted into the skin and connective tissue and allow better control of the stimulation intensities.
Building on previous research pointing to the role of neurotransmitters in regulating inflammation, researchers focused on two specific cell types that are known to secrete: chromaffin cells, which are located in the adrenal glands, and noradrenergic neurons, which are located in the peripheral nervous system and directly connected to the nervous system spleen through an abundance of nerve fibers. Chromaffin cells are the body’s main producers of the stress hormones adrenaline and noradrenaline, as well as dopamine, while noradrenergic neurons release noradrenaline. In addition to their well-established functions, adrenaline, noradrenaline and dopamine appear to play a role in the inflammatory response – an observation that has been confirmed in previous research and is now confirmed in the experiments of the current study.
The team wanted to determine the exact role of these nerve cells in the inflammatory response. To do this, they used a novel genetic tool to ablate chromaffin cells or noradrenergic neurons. This allowed them to compare the response to inflammation in mice with and without these cells to see if and how they were involved in modulating the inflammation. The markedly different reaction in mice with and without such cells clearly identified these nerve cells as key regulators of inflammation.
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In a series of experiments, the researchers used low intensity electroacupuncture (0.5 milliamps) at a point on the hind legs of mice with a cytokine storm caused by a bacterial toxin. This stimulation activated the vagus adrenal axis and induced the secretion of dopamine from the adrenal chromaffin cells. Animals treated this way had lower levels of three key types of inflammation-inducing cytokines and had higher survival than control mice – 60 percent of the acupuncture-treated animals survived compared with 20 percent of the untreated animals. Interestingly, the researchers observed that the vagus-adrenal axis could be activated by electroacupuncture of the hind legs, but not by abdominal acupuncture points – a finding that shows the importance of acupoint selectivity in controlling specific anti-inflammatory pathways.
In another experiment, the team performed high-intensity electroacupuncture (3 milliamps) on the same hind leg acupuncture point and on an acupuncture point on the abdomen of mice with sepsis. This stimulation activated noradrenergic nerve fibers in the spleen. The timing of treatment was critical, the researchers observed. A high-intensity stimulation of the abdomen led to significantly different results, depending on when the treatment was carried out.
Animals treated with acupuncture just before a cytokine storm developed had lower rates of inflammation and did better during the disease that followed. This preventive measure of high-intensity stimulation increased survival from 20 to 80 percent. In contrast, animals given acupuncture after the onset of the disease and during the peak of the cytokine storm showed worse inflammation and disease.
The results show how the same stimulus can produce dramatically different results depending on the location, time and intensity: “This observation underscores the idea that acupuncture, if used improperly, can have harmful consequences, which in my opinion people don’t necessarily appreciate”, said Ma.
If this is confirmed in further work, according to Ma, the results indicate the possibility that electroacupuncture could one day be used as a versatile treatment method – from additional therapy for sepsis in the intensive care unit to the more targeted treatment of site-specific inflammations, such as in inflammatory diseases of the gastrointestinal tract.
Another possible use, Ma said, would be to modulate inflammation following cancer immunotherapy, which, while lifesaving, can sometimes trigger a cytokine storm due to overstimulation of the immune system. Acupuncture is already used as part of integrative cancer treatment to help patients cope with the side effects of chemotherapy and other cancer treatments.
FURTHER MESSAGES ON THE TOPIC
Women benefit from self-help acupressure app 5th March 2018
Ötzi reveals acupuncture and progressive herbal medicine from the Neolithic Age 27. September 2018
Study proves the biological effect of acupuncture 4th July 2017
Study on back pain shows: fewer doctor visits and lower health insurance costs after acupuncture treatment March 14, 2012
Study: acupuncture helps with unexplained symptoms March 31, 2011
25 years of acupuncture therapy for allergy sufferers: Dresden method is scientifically recognized today 18. April 2011
Study shows how and why acupuncture changes brain activity December 3, 2010
Study proves effectiveness of acupuncture against stress in rats March 16, 2013
Those: Harvard Medical School
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