The Mechanism of Acupuncture - fascinating study

Recently published in Nature

The role of acupuncture in downregulation of pain and inflammation. An encouraging study published in Nature Magazine.

“A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis”

Liu, S., Wang, Z., Su, Y. et al. A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis. Nature 598, 641–645 (2021).

 By Aram Kopyan


New research is continuously shedding light on the effectiveness of acupuncture, yet there are still many questions as to the specific mechanisms involved in its efficacy. Recent research, which I will attempt to summarise may have discovered one such key mechanism. This will be a brief analysis and I urge the reader to review the original materials which contributed to this overview. The specific research deals with the pain and inflammatory mediating pathways that were identified which may have a specific role in the efficacy of acupuncture in downregulating inflammation and mediating pain. 


In order to understand the methods and significance of the experimental research discussed here it is important to establish some basic understanding of the various biological and neurological components involved in pain and inflammatory processes. “Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues.” (Liu et al. 2021) [1]. In other words, the neurons involved in the transmission and transduction of stimulatory signals including pain, terminate at various receptors. “Nociceptors, mechanoreceptors, thermoreceptors, and pruriceptors” (Basbaum et al., 2009, Delmas et al., 2011, Marmigère and Ernfors, 2007).

From the various proteins involved in the regulation of physiological processes within the living organism, several have been identified (Catecholamines) also known as chemokines, of which two specific proteins have been linked to the Prokineticin receptor 1 and 2 (PROKR1 and PROKR2) which are expressed in regions of the nervous system associated with pain and in cells participating in immuno-inflammatory responses. (Negri and Lattanzi 2012) [2]

Theoretical concept of the efficacy of acupuncture has been based on the idea that by stimulating (either manually or through electrical or optical means) a point, the physician can affect physiological and biological change in the homeostatic mechanisms of the body in general, and in specific locations. The theory is based on the as yet to be identified hypothetical meridian networks documented in various classic texts. Researchers have been attempting to explain the effects of acupuncture by means of the somatosensory autonomous reflexes. 

It is believed that stimulation of the receptors of specific sensitive neurons in certain areas of the body may be activating the reflex circuits of the autonomic nervous system (specifically Cranial Nerve X Vagus Nerve). In pursuing this line of experimentation, researchers at Harvard Medical School in collaboration with researchers from Fudan University and China Academy of Medical Sciences studied genetically modified line of mice to better isolate the role of PROKR2-Cre neurons. “Neurons were identified in the spinal ganglia, and more of them were found at the level of the extremities than at the level of the thoracic segments. In addition, these neurons could not be found in the sympathetic and intestinal ganglia and adrenal glands, while in the nodular ganglia they were found in minimal numbers (p <0.001). (Liu et al. 2021) [1] As shown in the illustration below, the researchers were able to demonstrate the anti-inflammatory effect of acupuncture (electroacupuncture) by utilizing these specific PROKR2-Cre neurons. Stimulation of the acupuncture point initiated a reflex chain through the ascending pathways to the nuclei of the Cranial Nerve X (vagus nerve) and activating the vagal-adrenal axis through descending pathways to initiate release of downregulatory catecholamines (epinephrine and norepinephrine), with anti-inflammatory effect. Researchers noted that “ST36 site can cause release of noradrenaline, adrenaline and dopamine from adrenal chromaffin cells that is dependent on the vagal nerve. And that electroacupuncture at ST36 causes “a 50% reduction in TNF and IL-6 induction and a 40% increase in survival rates compared with sham ES [electroacupuncture stimulation].” [1]


Further studies also illuminated the possibility that the stimulation of the acupuncture point may produce similar results when using light. “Optical stimulation of ST36 increased serum noradrenaline, adrenaline, and dopamine levels and suppressed proinflammatory cytokines. [1]


Experimental research though far from clinically proven means, serves an important role in identifying and spurring further development of methodologies and improving our understanding of Acupuncture and its role in health care. This discovery is another important milestone in establishing the mechanisms of acupuncture in pain and inflammatory regulation and further validates various clinical, observational and meta studies of its efficacy. It is an encouraging development to see prestigious scientific entities contributing to furthering of our understanding of a 5000-year-old medicine. 

[1] Liu, Shenbin, et al. “A Neuroanatomical Basis for Electroacupuncture to Drive the Vagal–Adrenal Axis.” Nature, no. 7882, Springer Science and Business Media LLC, Oct. 2021, pp. 641–45. Crossref, doi:10.1038/s41586-021-04001-4.

[2] Negri, Lucia, and Roberta Lattanzi. “Bv8/PK2 and Prokineticin Receptors: A Druggable Pronociceptive System.” Current Opinion in Pharmacology, no. 1, Elsevier BV, Feb. 2012, pp. 62–66. Crossref, doi:10.1016/j.coph.2011.10.023.


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