Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture

Neuron. 2020 Nov 11;108(3):436-450.e7. doi: 10.1016/j.neuron.2020.07.015. Epub 2020 Aug 12.


The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY+ noradrenergic neurons and/or adrenal chromaffin cells. Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- and intensity-dependent manners. Low-intensity ES at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY+ adrenal chromaffin cells. High-intensity ES at the abdomen activates NPY+ splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease-state-dependent changes in AR profiles. The revelation of somatotopic organization and intensity dependency in driving distinct autonomic pathways could form a road map for optimizing stimulation parameters to improve both efficacy and safety in using acupuncture as a therapeutic modality.

Keywords: ST25 and ST36 acupoints; adrenal chromaffin cells; adrenergic receptors; electroacupuncture; neuropeptide Y; somatosensory autonomic pathways; spleen; sympathetic neurons; systemic inflammation; vagal-adrenal axis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electroacupuncture*
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Neuropeptide Y / metabolism*
  • Sympathetic Nervous System / physiology*


  • Neuropeptide Y