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Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury

Weiguo Song, Alice Giannotti, Alexandra Bekiaridou, Ona Bloom, Stavros Zanos

Bioelectronic Medicine 2025 · 10.1186/s42234-025-00170-z

rodentchronic painbehaviourhistology molecular

Abstract

Low intensity, trans-spinal focused ultrasound (tsFUS) is a noninvasive neuromodulation approach that has been shown to modulate spinal circuit excitability in healthy rats. Here, we evaluated the potential of tsFUS for alleviating neuropathic pain by testing it in a chronic constriction injury (CCI) model. Male rats underwent CCI of the left sciatic nerve and then received tsFUS (2 kHz pulse repetition frequency; 40% duty cycle) or sham stimulation, targeted at spinal segment level L5 for 3 min daily over three days. As expected, CCI causes significant reduction of von Frey Threshold (vFT), a measure of mechanical sensitivity. We found that tsFUS treatment is associated with increased vFT compared to sham; this increase persists beyond the duration of treatment, through days 4 to 23 post-CCI. In spinal cords of tsFUS-treated animals, counts of spinal microglia (Iba1 + cells) and of activated, pro-inflammatory microglia (Iba1 + /CD86 + cells), are reduced compared to sham-treated animals. This reduction in microglia counts is limited to the insonified side of the spinal cord, ipsilateral to CCI. These findings suggest that tsFUS may be a promising approach for treatment of neuropathic pain at early stages, possibly by attenuating the development of microglial-driven inflammation.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects6, 5, 4swept animals
Sessions per subject3
Randomisednot reported
Blindingsingle
Sham / controlundescribed
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsbehaviour, histology molecular — von Frey threshold (dynamic aesthesiometer); Iba1 immunohistochemistry; CD86 flow cytometry of spinal microglia
Direction of effectinhibitoryEarly tsFUS after sciatic CCI was associated with recovery of von Frey threshold and fewer total and activated (CD86+) microglia ipsilateral to injury versus sham stimulation.
Adverse eventsnot reportedNo formal histological safety evaluation; a pilot test in a healthy rat showed no sign of tissue damage with the same protocol; animals were monitored daily for posture changes.

Exposures

Exposure 1: tsFUS at L5 spinal segment

Target: lumbar spinal cord — “L5 segment level of the spinal cord”
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)not reported⚑
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper)
Pulse repetition frequency (Hz)2,000✓✓✓
Duty cycle (%)40✓✓✓
Sonication duration (s)180✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

tsFUS delivered for 3 min daily on days 4, 5 and 6 after CCI under isoflurane; sham stimulation in controls.

Flags from extraction

  • n_subjects — 40 rats include sham CCI and CCI + sham-tsFUS animals; group sizes in cohorts are 4-6.
  • exposures[0].fundamental_frequency_khz — Carrier frequency, pressure and device not stated; refers to a previous paper.
  • exposures[0].timing.sonication_duration_s — 3 min per daily session recorded as 180 s.
  • direction_of_effect — Abstract says vFT increased; Fig. 2 legend says tsFUS animals show reduced VFT; direction in the text is recovery of threshold.