Therapeutic Effects and Mechanistic Insights of Low-Intensity Focused Ultrasound in Peripheral Neuropathic Pain
Tianqi Zhao, Jing Hu, Qiaoyu Zheng, Qi Shu, Junfeng Weng, Lian Yang, Yufeng Zhou, Min Feng
Journal of Pain Research 2026 · 10.2147/jpr.s617919
Abstract
Objective To investigate the therapeutic effects and underlying mechanisms of low-intensity focused ultrasound (LIFU) in peripheral neuropathic pain (NP). Methods Eight-week-old Sprague-Dawley rats were randomly assigned to four groups: Normal (no treatment), Sham (sciatic nerve exposure only), chronic constriction injury (CCI), and CCI + LIFU (LIFU applied after injury). Behavioral tests were conducted 7-9 days post-intervention. Rats were then anesthetized and sacrificed for dorsal root ganglion (DRG) collection. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to assess inflammatory cytokines. Electrophysiological changes were evaluated using electromyography and patch-clamp techniques at both nerve fiber and cellular levels. Results Compared with the CCI group, rats in the CCI + LIFU group showed significantly increased mechanical and thermal pain thresholds (n = 7, P P Conclusion LIFU can alleviate peripheral NP by inhibiting the transmission of pain signals from peripheral injury sites to the DRG, thereby achieving sustained blockade of nociceptive signaling and effectively reducing peripheral sensitization.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to CCI sciatic nerve (transcutaneous) and exposed nerve for EMG
Target: sciatic nerve — “sciatic nerve”
Device: other named manufacturer · Chongqing Haifu · SY23WX002 FU probe ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,745 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 100 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 0.5 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| Sonication duration (s) | 60, 180swept | ✓✓✓⚑ |
| 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) | 750 | ✓✓✓⚑ |
Transcutaneous stimulation for 3 min at 0.5 Hz PRF, 5% duty cycle (Figure 1 legend states 4 min); for EMG the exposed nerve was irradiated for 1 min with the same parameters. Frequency of treatment sessions not stated.
Exposure 2: LIFU to cultured DRG neurons
Target: dorsal root ganglion culture — “primary DRG neurons”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 200 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable | |
| Isppa, domain unspecified (W/cm²) | 0.05 | ✓?⚑ |
Cultured neurons exposed for 30 s at 1 Hz PRF, 20% duty cycle; recorded immediately or after 1 h or 2 h incubation.
Flags from extraction
n_subjects— n=7 per group for behaviour; n=5 for EMG/patch clamp and n=4 for ELISA; total rats exposed not stated (60 rats purchased).exposures[0].timing.sonication_duration_s— Methods say 3 min; Figure 1 legend says 4 min; EMG exposure was 1 min.exposures[0].unspecified_domain.pressure_kpa— 0.75 MPa given as acoustic pressure without stating domain.exposures[1].unspecified_domain.isppa_w_cm2— Given as acoustic intensity without stating metric (isppa vs ispta) or domain; placed in isppa.exposures[0].timing.pulse_duration_ms— Pulse duration not stated; at 0.5 Hz PRF and 5% DC the pulse would be 100 ms but not computed.anaesthesia— Anaesthesia during LIFU stimulation not stated (isoflurane used for surgery and terminal procedures).exposures[1].device— Device for patch-clamp culture exposure not named separately.