Researchers pinpoint how electroacupuncture targets inflammation

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"... In a 2014 study, researchers reported that electroacupuncture, a modern version of traditional acupuncture that uses electrical stimulation, could reduce cytokine storm in mice by activating the vagal-adrenal axis — a pathway wherein the vagus nerve signals the adrenal glands to release dopamine. ...
In a study published in 2020, Ma and his team discovered that this electroacupuncture effect was region specific: It was effective when given in the hindlimb region, but did not have an effect when administered in the abdominal region. ...

n their new study, the researchers conducted a series of experiments in mice to investigate this hypothesis. First, they identified a small subset of sensory neurons marked by expression of the PROKR2Cre receptor. They determined that these neurons were three to four times more numerous in the deep fascia tissue of the hindlimb than in the fascia of the abdomen.

Then the team created mice that were missing these sensory neurons. They found that electroacupuncture in the hindlimb did not activate the vagal-adrenal axis in these mice. In another experiment, the team used light-based stimulation to directly target these sensory neurons in the deep fascia of the hindlimb.

This stimulation activated the vagal-adrenal axis in a manner similar to electroacupuncture. “Basically, the activation of these neurons is both necessary and sufficient to activate this vagal-adrenal axis,” Ma said."

From the abstract:

"Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1,2,3,4,5,6 (for example, suppressing severe systemic inflammation6,7,8,9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1,2,3,4,5,6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal–adrenal anti-inflammatory axis in mice ...
Here we show that PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal–adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2Cre-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. ...
Furthermore, the distribution patterns of PROKR2Cre nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways."

Researchers pinpoint how acupuncture targets inflammation – Harvard Gazette Researchers discover neurons needed for acupuncture’s anti-inflammatory response

A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis (no public access)