Harvard Scientists Discover Neuroanatomical Basis for Acupuncture Signaling Pathway

Harvard scientists discovered the neuroanatomical basis for acupuncture points that trigger a specific anti-inflammatory signaling pathway, advancing the understanding of acupuncture’s therapeutic potential.

The team, led by Harvard Medical School neurobiologists, found the specific type of neuron — “PROKR2-Cre marked sensory neurons” — that must be present for acupuncture to trigger an anti-inflammatory response via the vagal-adrenal axis, a signaling pathway in the nervous system, according to their paper published in Nature last month.

In a study conducted on mice, the researchers showed that the PROKR2-Cre marked neurons only occur in an area of the hindlimb region, explaining why the anti-inflammatory response is not present in other regions of the body.

Senior author of the paper and HMS professor of neurobiology Qiufu Ma said that this discovery will allow scientists to predict the effectiveness of anti-inflammatory acupuncture treatment at different points of the body.

“Most importantly, based on the distribution of this fiber, we can predict where [it] will be effective,” Ma said.

The team was interested in a medical problem known as cytokine storm, which is triggered by diseases such as Covid-19 and cancer. A cytokine storm occurs when our immune response releases too many pro-inflammatory cytokines — small proteins important in cell signaling — which causes “collateral damage” in our bodies, according to Ma.

Ma pointed to a previous discovery which showed that “brief electrical stimulation” of the vagal-adrenal axis — a pathway in which the vagus nerve signals the adrenal gland to release dopamine, which reduces inflammation — via acupuncture increased survival in mice suffering from cytokine storm from 20 percent to around 75 percent.

The team hopes their study can open new doors for the optimization of this anti-inflammatory, therapeutic application of acupuncture, according to co-lead author and postdoctoral fellow Shenbin Liu.

“These findings could pave the way to optimization of bioelectronic stimulation parameters (eg. stimulation intensity, location and depth) to drive distinct autonomic pathways for treating specific diseases, including severe cytokine release syndromes, the management of which remains a major medical challenge,” Liu wrote in an email.

The next step for the team is to use their findings from the animal study and bring them back to a human context, according to Ma.

Ma said that the hope is that the “major nerve organization” between mice and humans is “evolutionary conserved” so that the parameters they discovered in mice can be used as guidance in future clinical studies.

—Staff writer Justin Lee can be reached at justin.lee@thecrimson.com.