Neuron
Volume 108, Issue 3, 11 November 2020, Pages 436-450.e7
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Article
Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture

https://doi.org/10.1016/j.neuron.2020.07.015Get rights and content
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Highlights

  • Intersectional genetic manipulation of NPY+ sympathetic cells

  • Electroacupuncture stimulation (ES) drives distinct sympathetic pathways

  • ES operates in somatotopy- and intensity-dependent manners

  • NPY+ noradrenergic neurons bidirectionally modulate systemic inflammation

Summary

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

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

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