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  • Writer's picturePhoebus Tian

New Mechanism for How Acupuncture Works Revealed

Updated: Mar 16

Clinical studies have shown that acupuncture has some modulatory effect on systemic inflammation. (Kwon 2012) One of the core mechanisms of acupuncture in treating disease is the remote regulation of body functions by stimulating specific areas of the body (acupoints). The meridians are considered a critical transmission vehicle for achieving this remote effect. Although modern anatomical studies have not yet clarified the existence of a meridian-specific structural basis, they have revealed that the remote effects of acupuncture can be achieved through somatosensory-autonomic reflexes.

In the late-1990s and early-2000s, Kevin Tracey and his team found that electrical stimulation of the cervical vagus nerve inhibited lipopolysaccharide (LPS)-induced inflammatory responses, revealed the connection between the nervous and immune systems.

How does the nervous system affect inflammation?

Inflammation is a normal response to injury and infection, but too much can damage tissue. You can see this in many diseases. As a result, the mammalian nervous system has evolved mechanisms to control inflammation. This includes signals from the vagus nerve to the brain to produce anti-inflammatory neurotransmitters.

What is the vagus nerve?

The vagus nerve is one of the twelve cerebral nerves that extend from the brain to the body, like a complex network of roots. These nerve networks act as communication between the brain and the many systems and organs of the body. Almost everything that people find relaxing (such as meditation and deep breathing) is associated with increased vagal nerve activity and parasympathetic nervous system activity.

In a new study published in Nature on 14th October, Professor Ma Qiufu from Harvard University and his team demonstrated the success of electroacupuncture stimulation of the ST36 point in animals to treat sepsis (septicaemia). It revealed that low-intensity acupuncture stimulation of mouse acupoints (足三里ST36) activated the vagal-adrenal anti-inflammatory pathway, while acupuncture stimulation of abdominal acupoints (天枢ST25) failed to induce this anti-inflammatory pathway. (Liu 2021)

This study achieves a historic breakthrough in acupuncture research, revealing a class of PROKR2-Cre-labelled DRG sensory neurons that are essential for low-intensity acupuncture stimulation to activate the vagal-adrenal anti-inflammatory pathway.

"Most Western medicine treats pain by hoping to suppress it by blocking nerve pathways. But we have a myriad of nerve pathways in our bodies, and a very large number of factors can activate each one. For many years, despite all the breakthroughs and achievements in animal experiments, we have not made any new drugs to treat pain." Professor Ma said. Inspired by the philosophy behind Chinese medicine of "treating the root cause of disease", Professor Ma and his team focused on inflammation, a significant cause of pain.

The researchers used a mouse model of inflammation in which the animals were injected with lipopolysaccharides to simulate a highly lethal systemic inflammatory disease that can be triggered by severe bacterial or viral infections: sepsis.

Electroacupuncture at different points can be predicted based on the somatic distribution characteristics of such nerves, thus providing a modern neuroanatomical basis for the relative acupuncture points.

The researchers accurately verified the structural basis of the anti-inflammatory effect induced by low-intensity electroacupuncture. It's based on the tissue innervation pattern of PROKR2-Cre-labelled sensory nerve fibres. In contrast to the dense projections in the fascial tissue near the tibia of the lower limb, the muscle tissue of the posterior lower limb, including the gastrocnemius of the lower leg and the semitendinosus of the thigh region, was poorly innervated by PROKR2-Cre sensory fibres. Low-intensity electroacupuncture on these sites failed to inhibit the LPS-induced inflammatory response significantly. There aren't many traditional acupuncture points on the gastrocnemius and semitendinosus muscles, where PROKR2-Cre nerve fibres are rarely found.

They also found that PROKR2-Cre-labelled sensory neurons also densely innervated deep fascial tissues of the forelimb, in this case, the LI 10 area of the hand, and they found that acupuncture stimulation of this point also significantly inhibited the LPS-induced inflammatory response. According to Master Nagano, this area is also called "Immune Point" in Japanese acupuncture.

The study suggests that choosing the correct points is essential for acupuncture stimulation to induce vagal-adrenal anti-inflammatory pathways. This relative specificity of acupuncture points is related to the distribution of PROKR2 nerve fibres. In addition, acupuncture intensity and depth(acupuncture techniques) are all important elements that influence the role of acupoints. These findings enrich the modern science of body surface stimulation therapies such as acupuncture and provide an essential scientific basis for the clinical optimisation of acupuncture stimulation parameters to induce different autonomic reflexes and thus treat specific diseases.

Acupuncture points have a bidirectional nature

In another study published on 12th August 2020 in Neuron (Liu 2020), Professor Qiufu Ma's research team found there is a bidirectional nature of the acupuncture modulatory effect: if high-intensity electroacupuncture stimulation is given to an abdominal acupoint (ST25) before the onset of LPS-induced systemic inflammation, it can exert a β2-norepinephrine receptor-mediated anti-inflammatory effect by activating peripheral NPY+ sympathetic neurons; whereas, after LPS-induced inflammation, application of the same abdominal acupoint and stimulation intensity exhibits a significant pro-inflammatory effect. In contrast, low-intensity acupuncture at ST36 inhibited the inflammatory response by activating the "vagus nerve-adrenal NPY+ medullary cell" pathway, both before and after LPS-induced inflammation.

"Our study reveals that electroacupuncture has a neuroanatomical rationale, but the safety and effectiveness of this treatment in humans needs to be further validated through clinical trials," said Professor Ma.


Kwon S, Lee B, Yeom M, Sur BJ, Kim M, Kim ST, Park HJ, Lee H, Hahm DH. Modulatory effects of acupuncture on murine depression-like behaviour following chronic systemic inflammation. Brain Res. 2012 7th September;1472:149-60. doi: 10.1016/j.brainres.2012.07.009. Epub 2012 13th July. PMID: 22796291.

Liu, S., Wang, Z., Su, Y. et al. A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis. Nature (2021).

Liu S, Wang ZF, Su YS, Ray RS, Jing XH, Wang YQ, Ma Q. Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture. Neuron. 2020 Nov 11;108(3):436-450.e7. doi: 10.1016/j.neuron.2020.07.015. Epub 2020 12th August. PMID: 32791039; PMCID: PMC7666081.

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