"Nature" is heavy: the neural mechanism of electro-acupuncture and moxibustion is in the top issue again!

Acupuncture, the mysterious eastern power
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Not only are we old Chinese doctors engaged in acupuncture, in fact, acupuncture is also very popular abroad in recent years, especially in the relief of pain-related diseases, and very good progress has been made
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However, although the effect of acupuncture has been verified to a certain extent, since modern anatomy has not been able to explain the existence of acupuncture points and meridians, it is not clear how acupuncture works
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Last year, Professor Ma Qiufu of Harvard Medical School published a paper in Neuron with scientists from Fudan University and the Institute of Acupuncture and Moxibustion of China Academy of Chinese Medical Sciences, revealing that acupuncture at different acupoints can activate different nerve pathways
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Today, the results of the same scientific research team were published in Nature[1].
This time, scientists even found specific PROKR2+ neurons related to acupuncture Zusanli, which provided a neuroanatomical basis for the existence of acupuncture points
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By analyzing specific neurons, we can also find acupuncture points with similar therapeutic effects
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In a paper published last year, the researchers discovered an interesting phenomenon
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Using electric acupuncture to stimulate Zusanli (ST36) and Tianshu (ST25) in mice, the mice produced completely different reactions
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Acupuncture Zusanli can activate the vagus nerve-adrenergic nerve and produce a significant anti-inflammatory effect
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So what is the difference between these two acupuncture points? Zusanli is located about two centimeters below the knee (of course the human body), that is, on the hind limbs, and Tianshu is located on the abdomen
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Researchers speculate that during acupuncture at Zusanli, the activation of the vagus nerve-adrenergic nerve is driven by a sensory-related circuit specific to the hind limbs
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Following this idea to explore, the researchers found the most critical neuron group, the dorsal root ganglion (DRG) neuron that expresses PROKR2
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PROKR2 neurons mainly exist in the deep fascia tissues related to the limbs, such as periosteum, joint ligaments and myofascial membranes, and do not regulate skin tissues and abdominal fascia tissues
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The researchers at Tianshu acupoint located in the abdomen and Zusanli located in the hind limbs successfully ablated PROKR2 neurons in the mouse DRG specifically without disturbing the neurons in the spinal cord and brain
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In normal mice, stimulation of Zusanli with 0.
5mA electric acupuncture can significantly activate the vagus nerve and induce the release of norepinephrine, epinephrine and dopamine from adrenal chromaffin cells
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But in PROKR2 ablation mice, this phenomenon is almost completely invisible
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After ablation of PROKR2 neurons, the therapeutic effect of acupuncture Zusanli disappeared
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In previous studies, researchers used electro-acupuncture at Zusanli to treat lipopolysaccharide (LPS)-induced systemic inflammation in mice
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In this experiment, stimulating Zusanli with 0.
5mA electric acupuncture can significantly reduce the levels of TNF and IL-6 in mice by 50%, and the survival rate of mice has also increased by 40%
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But in PROKR2 ablation mice, the therapeutic effect completely disappeared
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Acupuncture Zusanli significantly improves the survival of mice (left) after PROKR2 ablation, the effect disappears (right).
Interestingly, using a high current of 3mA to stimulate Zusanli can produce a therapeutic effect without the PROKR2 neurons
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Combined with the findings of other studies, perhaps high current intensity can induce other anti-inflammatory effects that do not depend on the vagus nerve
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The researchers also used optogenetics to further verify that the direct activation of PROKR2 neurons can fully drive the vagus nerve-adrenergic nerve axis, the mouse LPS-induced TNF and IL-6 are reduced by 50%, and the survival rate is increased by 50%.
%
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Obviously, PROKR2 neurons are the key to anti-inflammatory acupuncture
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Optogenetic activation of PROKR2 can reduce pro-inflammatory factors and improve the survival of mice.
So as long as PROKR2 neurons are present, other acupoints can also produce similar effects? PROKR2 neurons are concentrated near the fascia of the extremities and less in the back of the lower extremities
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Correspondingly, the gastrocnemius muscle on the back of the calf and the semitendinosus muscle on the back of the thigh are rarely distributed with traditional acupuncture points
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It seems reliable
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So the researchers used 0.
5mA electric acupuncture to stimulate the mouse hand Sanli (LI10), near it there are PROKR2 neurons that regulate the periosteum of the radius
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Sure enough, this also played a role in reducing TNF and IL-6
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In a review published in the same period of Nature[2], Luis Ulloa from Duke University analyzed that there are two mechanisms for the anti-inflammatory effect of stimulating the vagus nerve
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First, stimulate the adrenal glands to release dopamine and norepinephrine and other catecholamines to release into the blood; second, induce the spleen to produce norepinephrine and activate lymphocytes to secrete acetylcholine, which can inhibit the formation of splenic macrophages
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Compared with the systemic effects of many traditional drug treatments, catecholamines have a very short half-life (1-4 minutes), which can exert more precise therapeutic effects locally and avoid non-specific systemic effects
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Through electroacupuncture and moxibustion to selectively stimulate specific neural networks, it is possible to achieve precise local anti-inflammation.
For many people with chronic inflammatory diseases, it is a kind of anti-inflammation without suppressing the entire immune system to such an extent that Potential treatments that increase the risk of infection
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Reference materials: [1] https:// https:// Author of this article| Dai Siyu