Transcranial Focused Ultrasound Stimulation of Periaqueductal Gray for Analgesia
Tao Zhang, Zhen Wang, Huageng Liang, Zhengjie Wu, Jiapu Li, Jun Ou-Yang, Xiaofei Yang, Yuan Bo Peng, Benpeng Zhu
IEEE Transactions on Biomedical Engineering 2022, 69, 3155-3162 · 10.1109/tbme.2022.3162073
Abstract
Objective Transcranial focused ultrasound (tFUS) is regarded as a promising non-invasive stimulation tool for modulating brain circuits. The aim of this study is to explore the feasibility of tFUS stimulation for analgesia applications. Methods 50 µl of 3% formalin solution was injected into the rat's left hindpaw to build a pain model, and then the local field potential (LFP) activities of the dorsal horn were tracked after a recording electrode was placed in the spinal cord. Rats were randomly divided into two groups: control group and tFUS group. At the 30 th minute after formalin injection, tFUS (US-650 kHz, PD = 1 ms, PRF = 100 Hz, 691 mW/cm 2 ) was conducted to stimulate the periaqueductal gray (PAG) for 5 minutes (on 5 s and off 5 s) in the tFUS group, but there was no treatment in the control group. In addition, the analgesia mechanism (LFP recording from the PAG) and safety assessment (histology analysis) were carried out. Results The tFUS stimulation of the PAG can suppress effectively the nociceptive activity generated by formalin. The findings of the underlying mechanism exploration indicated that the tFUS stimulation was able to activate the PAG directly without causing notable temperature change and tissue injury. Conclusion The results illustrated that the tFUS stimulation of the PAG can achieve the effect of analgesia. Significance This work provides new insights into the development of non-invasive analgesic technology in the future.
Abstract via europepmc.
Exposures
Exposure 1: tFUS stimulation of the periaqueductal gray (PAG)
Target: periaqueductal gray — “periaqueductal gray (PAG)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | ⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 470 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.691 | ✓✓✓ |
tFUS (650 kHz, PD=1 ms, PRF=100 Hz, DC=10%) was applied to the PAG for a 5-min session structured as repeating 5-s-on/5-s-off cycles, beginning 30 min after formalin injection (or, in the separate mechanistic recording, delivered directly while an electrode recorded PAG LFP).
Flags from extraction
n_subjects— Paper states a total of 14 rats used in the study but only explicitly labels 6 as the tFUS (ultrasound-exposed) group in the main electrophysiology experiment; how the remaining rats (temperature measurement, PAG mechanism recording) were allocated to ultrasound exposure is not clearly separated.exposures[0].free_field.pressure_kpa— Only relative attenuation without skull (~25-29% of with-skull intensity) is given; no absolute free-field pressure/intensity value is stated in the text.