Quieting the storm

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A team of researchers led by neuroscientists at Harvard Medical School has successfully used acupuncture to tame systemic inflammation in mice.

In the study, published Aug. 12 in Neuron, acupuncture activated different signaling pathways that triggered either a pro-inflammatory or an anti-inflammatory response in animals with bacterially induced systemic inflammation.

Further, the team found that three factors determined how acupuncture affected response: site, intensity and timing of treatment. Where in the body the stimulation occurred, how strong it was and when the stimulation was administered yielded dramatically different effects on inflammatory markers and survival.

This represents a critical step toward defining the neuroanatomical mechanisms underlying acupuncture and offers a roadmap for harnessing the approach for the treatment of inflammatory diseases.

The scientists caution, however, that before any therapeutic use, the observations must be confirmed in further research — in animals as well as in humans — and the optimal parameters for acupuncture stimulation must be carefully defined.

“Our findings represent an important step in ongoing efforts not only to understand the neuroanatomy of acupuncture but to identify ways to incorporate it into the treatment arsenal of inflammatory diseases, including sepsis,” said study principal investigator Qiufu Ma, professor of neurobiology in the Blavatnik Institute at Harvard Medical School and a researcher at Dana-Farber Cancer Institute.

In the study, acupuncture stimulation influenced how animals coped with cytokine storm — the rapid release of large amounts of cytokines, inflammation-fueling molecules. The phenomenon has gained mainstream attention as a complication of severe COVID-19, but this aberrant immune reaction can occur in the setting of any infection and has been long known to physicians as a hallmark of sepsis, an organ-damaging, often-fatal inflammatory response to infection. Sepsis is estimated to affect 1.7 million people in the United States and 30 million people worldwide each year.

Acupuncture, rooted in traditional Chinese medicine, has recently grown more integrated into Western medicine, particularly for the treatment of chronic pain and gastrointestinal disorders. The approach involves mechanical stimulation of certain points on the body’s surface — known as acupoints. The stimulation purportedly triggers nerve signaling and remotely affects the function of internal organs corresponding to specific acupoints.

Yet, the basic mechanisms underlying acupuncture’s action and effect have not been fully elucidated.

The new study is an important step in mapping the neuroanatomy of acupuncture, the research team said.

As a neurobiologist who studies the fundamental mechanisms of pain, Ma has been curious about the biology of acupuncture for years. He was intrigued by a 2014 paper which showed that using acupuncture in mice could alleviate systemic inflammation by stimulating the vagal-adrenal axis — a signaling pathway in which the vagus nerve carries signals to the adrenal glands — to trigger the glands to release dopamine. Ma’s curiosity was further intensified by work published in 2016 showing that vagus-nerve stimulation tamed the activity of inflammatory molecules and lessened symptoms of rheumatoid arthritis.

In the current study, researchers used electroacupuncture — a modern version of the traditional manual approach that involves the insertion of ultra-thin needles just under the skin in various areas of the body. Instead of needles, electroacupuncture uses very thin electrodes inserted into the skin and into the connective tissue, offering better control of stimulation intensities.

Building on previous research pointing to neurotransmitters’ role in inflammation regulation, the researchers focused on two specific cell types known to secrete them — chromaffin cells that reside in the adrenal glands and noradrenergic neurons that are located in the peripheral nerve system and directly connected to the spleen through an abundance of nerve fibers.

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