Table 2 Preclinical usage of TNS in healthy conditions

Electrical, Distal Trigeminal Ganglion

15 isolated canine brains

50 Hz

10 V

1 ms PW

20 ms train

↑ CBF; ↓CVR

↑ Cerebral oxygen consumption

Lang and Zimmer 1974

Electrical, Trigeminal Ganglion

Adult cats

10 Hz

0.5 mA

0.25 ms PW

↑ CBF in the frontal and parietal cortex

Neurally controlled cortical vasodilation

Goadsby and Duckworth 1987

Male Wistar rats

5 Hz

10 V

1 ms PW

30 s continuous

Small increase in MAP and HR

Escott et al. 1995

Cats

0.5 – 20 Hz

0.25 mA

0.25 ms PW

30 s continuous

↓ CVR in the parietal cortex

↓ BP

Goadsby et al. 1997

Male Sprague–Dawley rats

1 mA

200 ms cycle

5 ms width

30 min continuous

↑ Plasma and cortical CGRP, PACAP, VIP, NPY, nociceptin

Guo et al. 2021

Invasive Electrical, Right Nasociliary Nerve

Adult Sprague–Dawley rats

3 – 60 Hz

5 V

0.5 ms PW

90 s continuous

↑ CBF as a function of frequency in the parietal cortex

Suzuki et al. 1990

Non- Invasive Electrical, Nasociliary Nerve

New Zealand albino rabbits of both sexes

10 Hz

5 V

0.5 ms PW

90 s continuous

↑ CBF as a function of voltage (1-5 V) in the premotor cortex

Gurelik et al. 2004

Percutaneous Electrical, Infraorbital Nerve

Male Sprague–Dawley rats

2 Hz

1.2 mA

1 ms PW

4 min continuous

↑ CBF in the barrel cortex

Pronounced increase in K1 and K2 of the H₂¹⁵O, which correlates to ↑ CBF

Weber et al. 2003

15 male Sprague–Dawley rats

0.25—12 Hz

2 mA

0.1 ms PW

↑ CBF as a function of frequency (up to 3 Hz) in the barrel cortex

Activation of somatosensory barrel field cortex above .5 Hz

Blood oxygen response reached maximum at 1 Hz and/or 1.3 mA

↓ BP above 3 mA

Just et al. 2010

Male Sprague–Dawley rats

50 Hz

0.25 – 5 V

.75 ms PW

Rectangular biphasic pulses

↓ HR; ↑ MAP; ↓SPO₂; ↑ rCBF; ↓ CVR; ↑ P_brO₂

↓RR; Brainstem Fos activation

Shah et al. 2020

Male Sprague–Dawley rats

133 Hz

0.25 – 3 V

1 ms PW

Rectangular biphasic pulses

60 s continuous

↑ CBF; ↓ CVR; ↑ MAP; ↑ CGRP; ↑ CPP

Li et al. 2021a, b

Infraorbital nerve, electrical acupuncture

12-week old Sprague–Dawley Rats

2/100 Hz

3 mA

6 s continuous for 40 min

↑ BBB permeability

↓ Occludin

↑ Calcium wave events with ↑ intensity

Gong et al. 2022

Peripheral trigeminal nerve stimulation

Adult female Wistar rats

5 Hz

0.05 mA

1 ms PW

10 s continuous

1 Hz

1—6 mA

0.1 ms PW

Both Settings:

↑ CBF

↑ Blood mean velocity

Li et al. 2009

Maxillary and mandibular branches

Adult female and male rats

0.05—1.5 mA

0.2 ms PW

Pseudorandom intervals of 3-4 s apart with different combinations

Both the Ion and SoN can be accessed through a single incision, and both can be accessed, interfaced, and engaged in rats

Dingle et al. 2019

Invasive Electrical, cut end of Lingual Nerve

Adult cats

10 Hz

30 V

2 ms PW

20 s continuous

 ↔ CBF; ↑ CCA BF

Sato et al. 1997

Adult male Wistar rats

1 – 30 Hz

1 – 30 V

2 ms PW

20 s continuous

↑ ICABF and LBF

Ishii et al. 2014