A Neuroanatomical Basis for Electroacupuncture to Drive the Vagal-adrenal Axis

Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites (for example, suppressing severe systemic inflammation). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal-adrenal anti-inflammatory axis in mice. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2-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 PROKR2-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 PROKR2-marked nerve terminals through the ST36 site is sufficient to drive the vagal-adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2 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.