Table 1.
Summary of the systematic literature review on antiinflammatory effects of VNS treatment in animal models and human trials.
| Ref | Sex | VNS site | Design | F (Hz) | A (V) | I (mA) | Pulse (ms) | Duration (min) | Effect | Persistence | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice | [11] | F | LCV | C | 20 | 0.8 | 0.5 | 0.5 |
|
A | |
| [12] | LCV | C | 5 | 1 | 2 | 20 (10 b/a LPS) |
|
C$$ | |||
| M | A | 5 | 1 | 2 | 2 (1 b/a LPS) | ||||||
| 5 | 1 | 2 | 0.5 (5 a/ LPS) | ||||||||
| 30 | 1 | 0.5 | 0.5 (5 a/ LPS) | ||||||||
| [13] | M | RCV | A | 1 | 2 | ? | 10 b/ |
|
A | ||
| [14] | |||||||||||
| [15] | M | RCV | A | 2 | Intermittently for 10 |
|
A | ||||
| [16] | M | RCV | A | 2 | 10 |
|
A | ||||
| [17] | M | RCV | A | 5 | 15 or 20 |
|
A | ||||
| [18] | M | LCV | C | 5 | 0.05 | 1 | 10 |
|
C$$$ | ||
| Rats | [6] | M | R/LCV | A | 1 | 5 | 2 | 20 (10 b/ and 10 a/ LPS) |
|
A | |
| [19] | M | LCV | A | 2 | 2 | 0.3 | 10 q45 b/ LPS |
|
A | ||
| [8] | M | LCV | A | 5 | 5 | 2 | 3 | = | A | ||
| [20] | M | LCV | A | 1 | 5 | 2 | 20 (10 b/ and 10 a/ LPS) |
|
A | ||
| [21] | M & F | LCV | C | 20 | 0.25 | 500 | 0.5 q5 for 3 h per d from d 1 to d 6 |
|
A | ||
| [22] | M | LCV | A | 1 | 5 | 2 | 20 a/ LPS |
|
A | ||
| [23] | M | R heart | A | 5 | 2–6 | 1 | 15 b/ and 120/a |
|
A | ||
| [24] | M | RCV | A | 8–10 | 2.5 | 0.5 | 40 |
|
A | ||
| [25] | M | R/LCV | A | 1 | 5 | 2 | 15 b/ and a/ 6 h |
|
C$ | ||
| [26] | M | R/LCV | A | 1 | 5 | 2 | 20 a/ LPS |
|
A | ||
| [27] | M | LCV | A | 5 | 10 | 2 | 20 a/ |
|
C | ||
| [28] | M | RCV | A | 5 | 15 | 2 | 20 |
|
A | ||
| [29] | M | RCV | A | 1 | 5 | 2 | Either 20 starting 5 b/ LPS or 2 (1 b/ and 1 a/ LPS) |
|
A | ||
| [30] | - | LCV | A | 10 | 0.0005 | 1s | 0.3 b/ 45 a/LPS |
|
A | ||
| [31] | M | LCV | A | 2 | 2 | 0.3 | 10 q45, starting right b/ LPS, until 4.5 h a/ LPS |
|
A | ||
| [32] | M | RCV | A | 20 | 0.5 | 0.5 | 0.5 train q5 for 30 |
|
C | ||
| [33] | - | LCV | A | 10 | 0.5 | 1000 | 0.02 with 500 μs bipolar stimul q0.3 for 10; repeat 10 a/ LPS for 45 b/ break of 3 h |
|
A | ||
| [34] | M | RCV | A | 5 | 5 | 10 |
§
|
C | |||
| [35] | F | LCV | C | 20 | 1 | 10 | 3 h at same time every other day, beginning 1 wk after operation for 12 wks |
|
A | ||
| [36] | M | RCV# | A | 25 | 7.2 | 1 | 2 q10 for 60 |
|
A | ||
| [37] | M | RCV | A | 10 | 1.0–7.0 | N/A | 2 | N/A |
|
A | |
| Pigs | [38] | M | R/LCV | A | 3 | 1 | 0.2 | n/a | |||
| Dogs | [39] | M and F | RCV | C | 20 | 0.75–2.5 | 0.5 | 14 s on 12 s off continuously for 8 wks |
|
A | |
| [40] | F | RCV | A | 1 or 2 | 0.02–50 | 0.3 | 0.006 | n/a | |||
| Humans | [41] | M and F | LCV | C | 1–145 | - | 0.25–4 in 0.25 steps | 130–1000 | 7–270 s in 30 s steps |
|
C |
| [9] | M and F | LCV | C | 30 | 0.75–1.75 | 500 | 0.5 on 5 s off for 3 months | = | A | ||
| [10] | M | LCV* | A | 20 | 0–10 | 1 | Continuously for 30 | = | C | ||
| [42] | M and F | LCV | A** | 20 | 1 | 0.5 | 0.5 |
|
A | ||
| C*** §§ | 10 | 0.25–2 | 0.25 | 1 |
|
C§§ |
Abbreviations: F, frequency, Hz; A, amplitude, volt; I, intensity, milliampere; Pulse, duration of a VNS pulse; Duration, duration of VNS stimulation treatment; A, acute effect <24 h (on inflammation); C, chronic >24 h (on the experimental endpoint);
, R of inflammation due to VNS; =, no effect; RCV, right cervical vagus; LCV, left cervical vagus
Catheter inserted in the left internal jugular vein at spinal level 5-C7, adjacent to the vagus nerve
Epilepsy cohort
Rheumatoid arthritis cohort
Skin overlying the right cervical vagus nerve
Improvement of renal function at three days, return to control at five days
Reduced (except in α7nAChR knockout mice)
Acute design for epilepsy cohort; chronic design for rheumatoid arthritis cohort
48 h but not 72 h
VNS 10 min b/ischemia resulted in no protection; protective effects for at least two days