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. 2023 Dec 13;9:30. doi: 10.1186/s42234-023-00128-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — The effects, therapeutic targets, and unique properties of TNS. The effects of TNS can be separated into 3 main categories: effects on the CNS, the ANS, and the peripheral vasculature. Based on these effects, and particularly the effects on the CNS, many current therapeutic targets are focused on neurological, psychological, neuromuscular, and cerebrovascular pathologies. Already, some are approved for clinical usage, and others are in clinical testing. TNS is also currently under preclinical trials for acute/traumatic conditions, such as TBI, stroke, and hemorrhagic shock. Its multitudinous effects may allow it to be used therapeutically for the treatment of retinopathy, spinal cord injury, inflammatory dysfunctions, chronic cerebral hypoperfusion, and drug addiction. Setting it apart from other forms of bioelectronic medicine, TNS is able to cause direct cerebrovasodilation, increase hypocretin expression, and induce peripheral vasoconstriction. It is also the only one so far tried for balance difficulties due to mTBI. Uniquely, TNS also has diagnostic potentials in regard to Parkinson’s disease and hemorrhagic shock severity, which broadens its potential applications. (This figure was generated using BioRender.com) (ADHD: attention deficit and hyperactivity disorder; BBB: blood–brain barrier; CNS: central nervous system; CSD: cortical spreading depolarization; HS: hemorrhagic shock; IBD: irritable bowel disease; mTBI: mild traumatic brain injury; PNS: parasympathetic nervous system; PTSD: post-traumatic stress disorder; PVS: persistent vegetative state; SAD: social anxiety disorder; SAH: subarachnoid hemorrhage; SNS: sympathetic nervous system TBI: traumatic brain injury; TNS: trigeminal nerve stimulation)