Table 1.

Clinical usage of TNS

Status	Medical Condition	Stimulation Method	Population	Stimulation Parameters	Observations	Adverse Events	Reference
Clinical Usage	Migraine	Infratrochlear nerve	Healthy, common migraine, episodic CH, and inactive phase of CH	40 mA 0.8 ms PW	Significant ipsilateral pupillary miosis	None stated	Fanciullacci et al. 1989
		Subcutaneous supraorbital and occipital nerve	Patients with CM	Not stated	↓ Pain and neurological symptoms	None stated	Reed et al. 2010
		Bilateral supratrochlear and supraorbital nerves with Cefaly	Migraine with or without aura	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Migraine severity and frequency	None stated	Schoenen et al. 2013
		Cefaly—Transcutaneous Supraorbital Nerve	Chronic Migraine, 60% with medication overuse	100 Hz 16 mA 0.25 ms Pw	↓ Muscle EMG	None stated	Didier et al. 2015
				60 Hz 16 mA 0.3 ms PW
		Cefaly—Transcutaneous Supraorbital Nerve	67 episodic migraine patients	60 Hz 16 mA 0.25 ms PW 20 min per day	↓ Migraine days	Paresthesia reported	Reiderer et al. 2015
		Cefaly supraorbital and supratrochlear stimulation	24 patients with migraine without aura	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Migraine severity and frequency ↓ HIT-6 questionnaire rating	None stated	Russo et al. 2015
		3 months Cefaly—Transcutaneous Supraorbital Nerve	28 individuals Episodic Migraine	60 Hz 16 mA 0.25 ms PW 20 min daily for 3 months	↓ Migraine days ↓ Hypometabolism in OFC and rACC	None stated	Magis et al. 2017
		Cefaly eTNS	30 patients diagnosed with migraine with or without aura	100 Hz 16 mA 0.25 ms PW 60 min/day	↓ Pain intensity	None stated	Chou et al. 2017
		Cefaly	Chronic migraine	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Frequency ↓ Medication usage	None stated	Di Fiore et al. 2017
		Cefaly—Transcutaneous Supraorbital Nerve	109 Participants	100 Hz 16 mA 0.25 ms PW 1 h	↓ Pain scores	None stated	Chou et al. 2019
		Transcutaneous supraorbital nerve stimulation (Cefaly)	Migraine w/out aura	60 Hz 16 mA 0.25 ms PW 20 min/day	Strong placebo effect was noted	None stated	Vecchio et al. 2018
		Cefaly on supratrochlear and supraorbital of ophthalmic	Vestibular migraine	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Vertigo and headache ↓ Symptoms	None stated	Beh 2020
		Supraorbital and supratrochlear nerve electrostimulation	25 participants with CM	60 Hz 16 mA 0.25 ms PW 20 min/day	↑ Sleep ↓ Pain severity and frequency	Some paresthesia, unpleasant dysesthesias, mild dizziness, mild nausea, somnolence	Ordas et al. 2020
		Cefaly eTNS	Patients with CM	100 Hz 16 mA 0.25 ms PW 120 min/day	↓ Headaches	Only minor AEs, such as paresthesia	Kuruvilla et al. 2019
		Cefaly eTNS	18 patients with ocular pain with/without CM	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Ocular pain intensity ↓ Light sensitivity ↓ Wind sensitivity ↓ Burning sensation	Sedation	Mehra et al., 2021
		Cefaly eTNS	24 patients with CM	60 Hz 16 mA 0.25 ms PW 20 min/day	↓ Headache days	None stated	Trimboli et al. 2023
	pediatric ADHD	8-week NeuroSigma Monarch eTNS – bipolar V1 stimulation	Adolescents aged 7–14 with DSM IV ADHD	120 Hz 0.25 ms PW 30 s on 30 s off 7 – 9 h per night	↓ Inattentive and hyperactivity ↑ Height, weight, pulse	None stated	McGough et al. 2019
	Balance difficulties due to mTBI	Helius Medical PONS-Translingual eTNS	Adults	Not stated	↓ SOT, DGI, and 6MWT scores	2 mild and 6 moderate AEs	Tyler et al 2019
		Translingual neurostimulation	Adults with mTBI diagnosis and balance deficit	High Freq: 150 Hz 0.4—60 µs PW 5 ms interval	↑ DGI scores ↓ HDI and SQI	None stated	Ptito et al. 2021
				Low Freq: 0.08 Hz 12.5 s interval
Clinical Trials/ Testing	Drug Resistant Epilepsy	Unspecified	2 patients	120 Hz 8 – 25 mA 20 – 30 s on 20 – 30 s off 24 h	↓ Seizures	None stated	DeGiorgio et al. 2003
		NeuroSigma Monarch eTNS – bipolar stimulation at ophthalmic and supratrochlear nerves	Patients with 2 or more partial onset seizures per month	120 Hz 0.25 ms PW	↓ In seizure frequency Mood improvement	Anxiety, headache, and skin irritation	DeGiorgio et al. 2013
			Patients with DRE	120 Hz 7/30 s  > 8 h/day	↑ Quality of life	No severe adverse events	Slaght et al. 2017
			Patients with DRE, use of at least 1 AED	Not stated	↑ Sleep, mood, and energy ↓ Seizures	None stated	Olivie et al. 2019
			Patients with DRE	120 Hz  < 10 mA 0.25 ms PW 30 s on 30 s off At least 8 h/day	↑ Quality of life ↓ Seizure rates	No severe adverse events	Gil-Lopez et al. 2020
		Unspecified	Patient with DRE which progressed to RSE	None stated	Improved mental status ↓ Seizures	No severe AE	Moseley et al. 2014
		APEX set for neuromodulation	Patients with DRE	120 Hz 0.25 ms PW 5 s on 5 s off	↓ Seizures	No severe AE	Zare et al. 2014
		Winner stimulator	29 subjects with DRE	120 Hz 1 – 20 mA 0.25 ms PW 30 s on 30 s off 20 min	↑ Absolute power of alpha band in the parietal-occipital areas	None stated	Ginatempo et al. 2019
	Depression	8 weeks external trigeminal nerve stimulation (NeuroSigma predecessor)	Pharmacological resistant major depression	Not stated	↓ HDRS and BDI scores	None stated	Schrader et al 2011
		NeuroSigma Monarch eTNS	Adults with nonpsychotic unipolar MDD	120 Hz 4 – 6 mA 0.25 ms PW 30 s on 30 s off	↑ Quality of life ↓ Depression test scores	No severe adverse events	Cook et al 2013
			Patients diagnosed with MDD	120 Hz 0 – 100 mA 0.25 ms PW Cycle of 30 s	↓ Depression test scores	No severe adverse events	Shiozawa et al 2014a, b
		10 Days Ibramed Neurodyn eTNS- V1 TENS stimulation	Patients between 18 and 69 with severe MDD	120 Hz 0 – 100 mA 0.25 ms PW Cycle of 30 s	↓ Depressive symptoms	None stated	Generoso et al 2019
	Fibromyalgia	10 days of bilateral supraorbital stimulation	Patient with fibromyalgia	120 Hz 0.25 ms PW 30 min	↓ Pain ↓ Depressive symptoms	None stated	Shiozawa et al. 2014a, b
	Social Anxiety Disorder (SAD)	10 days supraorbital electrostimulation	Patient with SAD	120 Hz 0.25 ms PW 30 min continuous	↓ Avoidance behaviors ↓ SPIN and LSAS scores	None stated	Trevizol et al. 2015
	PTSD	Bilateral trigeminal nerve electrostimulation	5 patients with PTSD and MDD	120 Hz 0.25 ms PW 30 min/day	↓ PTSD and depressive symptoms	No serious AE reported	Trevizol et al 2015
		NeuroSigma Monarch eTNS	Adults with both PTSD and MDD, 18–75 in age	120 Hz 4 – 6 mA 0.25 ms PW 30 s on 30 s off 8 h each night	↓ PCL score	None stated	Cook et al 2016
	Cognitive/ Sensory Dysfunction Secondary to Other Pathologies	Portable Neuromodulation Stimulator (PoNS™)	14 MS patients	Not stated	↑ SOT scores ↑ BOLD in bilateral premotor areas	None stated	Leonard et al. 2017
		EA/TNS for 15 acupoints (some on trigeminal facial nerves)	Females 18–65 with breast cancer, either undergoing or finished chemo less than 2 weeks ago	2 Hz 6 V, 48 mA 0.1 ms PW 30 min	↓ Diarrhea, tenseness, worriness, irritation, headache, and tinnitus	None stated	Zhang et al. 2020
	Persistent Vegetative State	Ophthalmic nerve and maxillary nerve	Patients in PVS	40 Hz 18 – 20 mA 0.2 ms PW 30 s/min 6 h/day	Spontaneous eye opening and exclamatory articulated speech after 4 weeks of TNS ↑ GCS scores	None stated	Fan et al. 2019
		Suborbital foramen and bilateral superior orbital fissures	Patients with Disorders of Consciousness	40 Hz 18 – 20 mA 200 ms PW 30 s/min	Signs of recovery	None stated	Dong et al. 2022
		Bilateral maxillary and mandibular nerve	Patients with DOC after suffering TBI	40/28 Hz 8 mA 40 min	↑ CRS-R scores	None stated	Wu et al. 2022
		Bilateral supraorbital foramen and infraorbital foramen	Patients in PVS	40 Hz 10 – 15 mA 0.2 ms PW 30 s/min 3 h/day	↑ Recovery ↑ Total GCS and CRS-S scores ↓ Hypometabolic areas	None stated	Ma et al. 2023
	Subarachnoid Hemorrhage	Supratrochlear and supraorbital transcutaneous electrical stimulation	Patients with SAH	20 Hz 14 days Continuous	No significant effects on vasospasm-related DCI, functional outcome, and health-related quality of life	None stated	Rigoard et al. 2023
	Parkinson’s Disease	Gaseous CO2	Healthy adults and Patients with olfactory dysfunction due to PD	Unilateral nasal exposure 200 ms 145 mL/s	Trigeminal olfactory event related potentials were the same between healthy and PD individuals	None stated	Barz et al. 1997
		Eucalyptol	Healthy adults and Patients with olfactory dysfunction due to PD	Unilateral nasal exposure	Trigeminal sensitivity was the same in healthy and PD individuals	None stated	Tremblay et al., 2017
	Healthy	nuroStym device at the right forehead and cheek	Healthy adults	350 Hz 3.5 mA 10% DC 20 min	Slight decrease in creatine concentrations in the DLPFC region	None stated	Ritland et al. 2023
		Minimally Invasive Electroacupuncture, Supraorbital nerve	Healthy adults	100 Hz 0.1—0.2 mA 0.25 ms PW 5 cycles of 1 min on 1 min off for 15 min	↑ CBF in the prefrontal cortex ↑ Oxygenated Hb in PFC ↓ Deoxy Hb in R-PFC ↓ HR w/ EA	None stated	Suzuki et al. 2020
		Ophthalmic nerve	Healthy adults	120 Hz 30 s/min 30 min continuous	↓ Mean olfactory detection threshold ↓ Sleepiness	None stated	Badran et al. 2022
		Ophthalmic nerve	Healthy adults	3 kHz 50 ms PW 30 s/min 20 min	No significant effect on learning	None stated	Arias et al. 2022
		Opthalmic nerve + Transcranial Magnetic Stimulation	Healthy adults	120 Hz 1.8–6.8 mA 0.25 ms PW 40 min	↔ Cortical excitability	None stated	Axelson et al. 2014
		Infraorbital nerve	17 Healthy adults	120 Hz 1 – 20 mA 0.25 ms PW 30 s on 30 s off for 20 min	↓ R2 area  ↔ R1 area  ↔ R2 recovery cycle  ↔ Intracortical excitability	None stated	Mercante et al. 2015
		Infraorbital nerve	20 Healthy adults	120 Hz 1 – 20 mA 0.25 ms PW 30 s on 30 s off for 20 min	R2 blink response inhibited up to 60-min after TNS	None stated	Pilurzi et al. 2016
		Infraorbital nerve	18 Healthy adults	120 Hz 1 – 20 mA 0.25 ms PW 30 s on 30 s off for 20 min	↓ Beta-frequency intra- and interhemispheric coherences ↑ EEG frequency total power ↓ Interhemispheric gamma coherence	None stated	Ginatempo et al. 2018
		Infraorbital nerve	15 Healthy adults	120 Hz 6 – 18 mA 0.25 ms PW 30 s on 30 s off for 20 min	↓ Hand-blink reflex magnitude	None stated	Mercante et al. 2020
		Supraorbital nerve	Healthy adults	400 Hz Variable intensity	Blink potentiation for > 1 h	None stated	Mao and Evinger, 2001
		Infraorbital nerve	Healthy adults	120 Hz 1 – 20 mA 0.25 ms PW 30 s on 30 s off for 20 min	No significant increases in measured ERP components	None stated	Mercante et al. 2023
		Trigeminal stimulation with gaseous CO2	12 normosmic and 11 anosmic	Not stated	Activation of cerebellum and premotor cortex, PFC, anterior cingulum, cingulate gyrus, insula	None stated	Iannilli et al 2007
		CO2 trigeminal stimulation	19 healthy	N/A	Activation of insula, middle frontal gyrus, and supplemental motor area, midbrain, DOFC, frontal operculum, superior temporal gyrus, medial frontal gyrus, and anterior caudate nucleus	None stated	Hummel et al 2005
		Facial cooling	Healthy adults	N/A	↓ HR	None stated	Janczak et al. 2022
		Facial cooling	Healthy adults	N/A	↑ CBV ↓ HR ↑ BP ↑ Coronary circulation	None stated	Prodel et al 2023