Trigeminal Nerve Stimulation for Disorders of Consciousness: A Narrative Review of Potential Mechanisms, Clinical Evidence, and Future Perspectives.
5 affiliations
- 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- 2School of Instrumentation Science and Opto-Electronics Engineering, Beijing Information Science and Technology University, Beijing, China.
- 3Department of Neurosurgery, The People's Hospital of Liaoning Province, Liaoning, China.
- 4Department of Neurosurgery, Aviation General Hospital, Beijing, China.
- 5Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Abstract
Background
Disorders of consciousness (DoC), including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS), present a major clinical challenge due to limited therapeutic options. Trigeminal nerve stimulation (TNS) has recently emerged as a promising neuromodulatory intervention.Mechanisms and current evidence
The trigeminal nuclei send efferent fibers to the thalamus and the ascending reticular system, which then broadly innervate multiple brain areas via the ascending reticular activating system (ARAS) through both direct and indirect pathways. Capitalizing on the trigeminal nerve's distinctive anatomy, TNS has been hypothesized to potentially promote consciousness recovery in preclinical models by activating specific pathways, modulating the release of key neurotransmitters (e.g., hypocretin, dopamine, and norepinephrine), and influencing cerebral hemodynamics. Furthermore, randomized controlled trials (RCTs) involving both external TNS (eTNS) and acoustic-electric TNS have highlighted a possible direction for its application as a novel therapy for DoC; the findings appear to suggest potential clinical relevance, although current evidence remains constrained by small samples, patient heterogeneity, variable stimulation protocols, and limited long-term follow-up.Challenges
The clinical translation of TNS, however, faces pressing obstacles, including uncertainty regarding optimal stimulation targets and parameters, insufficient long-term safety and efficacy data, incompletely elucidated mechanisms of action, and a lack of suitable preclinical models.Conclusions
TNS may represent a promising therapeutic approach for DoC, but further high-quality studies are needed to establish its mechanisms, safety, efficacy, and optimal stimulation strategies.
Related
- Effects of single-modality sensory stimulation on brain function in patients with prolonged disorders of consciousness: a near-infrared spectroscopy-based study
- Deep brain stimulation and spinal cord stimulation for chronic disorders of consciousness: a decade of clinical evidence, mechanistic insights, and critical appraisal.
- Effects of auditory sensory stimulation on consciousness and physiological parameters among individuals with disorders of consciousness: a systematic review and meta-analysis
- EEG-defined differences in functional networks following beta-band transcranial alternating current stimulation in patients with disorders of consciousness: a pilot study.
- Transcutaneous auricular vagus nerve stimulation in perioperative neurocognitive disorders: clinical evidence and mechanistic perspectives
BibTeX
@article{niu2026trigeminal,
title = {{Trigeminal Nerve Stimulation for Disorders of Consciousness: A Narrative Review of Potential Mechanisms, Clinical Evidence, and Future Perspectives.}},
author = {Haodong Niu and Yilin Zhang and Nan Wang and Xiaoke Chai and Yiyi Zhai and Zhiyao Zheng and Yangxi Xu and Yitong Jia and Kefei Wan and Sipeng Zhu and Tianqing Cao and Qiheng He and Minghao Liu and Zhuoyang Li and Yichen Wang and Haitao Huang and Juanning Si and Yi Yang and Jizong Zhao},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71148},
url = {https://europepmc.org/article/MED/42902880},
note = {CC BY},
}
RIS
TY - JOUR
TI - Trigeminal Nerve Stimulation for Disorders of Consciousness: A Narrative Review of Potential Mechanisms, Clinical Evidence, and Future Perspectives.
AU - Haodong Niu
AU - Yilin Zhang
AU - Nan Wang
AU - Xiaoke Chai
AU - Yiyi Zhai
AU - Zhiyao Zheng
AU - Yangxi Xu
AU - Yitong Jia
AU - Kefei Wan
AU - Sipeng Zhu
AU - Tianqing Cao
AU - Qiheng He
AU - Minghao Liu
AU - Zhuoyang Li
AU - Yichen Wang
AU - Haitao Huang
AU - Juanning Si
AU - Yi Yang
AU - Jizong Zhao
PY - 2026
DA - 2026/10/01
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71148
UR - https://europepmc.org/article/MED/42902880
AB - Background Disorders of consciousness (DoC), including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS), present a major clinical challenge due to limited therapeutic options. Trigeminal nerve stimulation (TNS) has recently emerged as a promising neuromodulatory intervention.Mechanisms and current evidence The trigeminal nuclei send efferent fibers to the thalamus and the ascending reticular system, which then broadly innervate multiple brain areas via the ascending reticular activating system (ARAS) through both direct and indirect pathways. Capitalizing on the trigeminal nerve's distinctive anatomy, TNS has been hypothesized to potentially promote consciousness recovery in preclinical models by activating specific pathways, modulating the release of key neurotransmitters (e.g., hypocretin, dopamine, and norepinephrine), and influencing cerebral hemodynamics. Furthermore, randomized controlled trials (RCTs) involving both external TNS (eTNS) and acoustic-electric TNS have highlighted a possible direction for its application as a novel therapy for DoC; the findings appear to suggest potential clinical relevance, although current evidence remains constrained by small samples, patient heterogeneity, variable stimulation protocols, and limited long-term follow-up.Challenges The clinical translation of TNS, however, faces pressing obstacles, including uncertainty regarding optimal stimulation targets and parameters, insufficient long-term safety and efficacy data, incompletely elucidated mechanisms of action, and a lack of suitable preclinical models.Conclusions TNS may represent a promising therapeutic approach for DoC, but further high-quality studies are needed to establish its mechanisms, safety, efficacy, and optimal stimulation strategies.
SN - 1755-5930
SN - 1755-5949
ER -