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

Maybe it sounds hyperbolic, but this article is a true breakthrough.

As patients and readers of the blog know, I’ve been focused on the relationship between autonomic balance/stress response and acupuncture for a long time.  I measure Heart Rate Variability (HRV), a measure of autonomic balance in the clinic routinely.  I have always been interested in Immunology because of my severe allergies (which acupuncture subsequently cured).   It turns out, as I lay out in my most recent chapter of my writing project,  researchers have recently shown that there is a reflex called the Neuro-Endocrine-Immune response.  This reflex is caused by injury which triggers pain fibers which communicate with the spinal cord and brain stem which then stimulate the vagus nerve to feed back on the injured area and control inflammatory response.  It is a key part of homeostasis to keep the body from overreacting to an injury.

Basically, this article shows that one of the most used points in acupuncture,  Susanli or Stomach 36 is close to the deep peroneal nerve which has certain markers on it, PROKR2Cre-marked sensory neurons.  As it turns out, these type of neurons respond to low intensity electro acupuncture by activating hind brain vagal efferent fibers.  Other types of sensory fibers, say on the abdomen, do NOT activate the vagal fibers.

This is huge in a number of ways.

1. Because of the NEI, discussed above, I had always thought that maybe a lot of acupuncture needling had a general effect on causing a “rest and digest” response.  Though I always use time honored acupuncture points, I thought that there was benefit from needling in general.
2. This study shows that all points are NOT created equal. That there are different responses to different points.
3. There also seems to be specificity of the type of stimulation.  High frequency does not cause a vagal enhancement, where low frequency does at Susanli.  This is similar to transcutaneous vagal auricular stim (TAVNS) where you need to make sure no pain fibers are triggered only touch fibers.  In the case of Susanli, mild stimulation is best, though for different reasons.
4. It is unclear if it would be possible to measure this same vagal enhancement with HRV.  But you can be sure I will try.

Liu_et_al-2021-specific acupoints Nature

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

Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1–6 (for example, suppressing severe systemic inflammation6–9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1–6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal–adrenal anti-inflammatory axis in mice10,11. The neuroanatomical basis of this somatotopic organization is, however, unknown. 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. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2Cre-marked nerve terminals through the ST36 site is sufficient to drive the vagal–adrenal axis but not sympathetic reflexes. 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.