Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex
Bin Wang, Mo-Xian Chen, Shao-Chun Chen, Xiang-Jun Feng, Ye-Hui Liao, Yun-Xin Zhao, Jin-Shan Tie, Yao Liu, Li-Juan Ao
Neural Plasticity 2022 · 10.1155/2022/6472475
Abstract
Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT 50 ) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells ( P 50 decreased significantly ( P 50 were found in the CCI+LIFU group compared with the CCI group ( P P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to ACC
Target: anterior cingulate cortex — “anterior cingulate cortex (ACC)”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 4,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.0667 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | 10 | ✓✓✓ |
| Sonication duration (s) | 900 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 950 | ✓✓✓⚑ |
LIFU administered for 15 min/day for 21 days starting on day 91 after CCI surgery, under isoflurane anaesthesia, with a collimator placed over the ACC.
Flags from extraction
n_subjects— 42 mice in total includes controls: 6 LIFU(+) and 6 LIFU(-) safety mice and 10 each in sham, CCI and CCI+LIFU; the LIFU-exposed groups total 16.exposures[0].unspecified_domain.pressure_kpa— Reported as 'acoustic intensity of 0.95 MPa' measured with a hydrophone; medium and domain not stated.exposures[0].timing.sonication_duration_s— 15 min/day recorded as 900 s; whether sonication was continuous within that period is not stated.exposures[0].timing.pulse_duration_ms— Not stated; not computed from DC and PRF.exposures[0].device.family— No transducer maker named; hydrophone (Onda) and amplifier makers are not the transducer's.sham_type— CCI group received LIFU with the transducer turned off; sham group received anaesthesia only.