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Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury

Abigail Hellman, Teresa Maietta, Kanakaharini Byraju, Yunseo Linda Park, Andrea Liss, Tarun Prabhala, Paul Neubauer, Emery Williams, Clif Burdette, Damian S. Shin, Goutam Ghoshal, Julia Nalwalk, Aira Agrawal, Jiang Qian, Julie Pilitsis

Neuroscience 2020 · 10.1016/j.neuroscience.2020.01.016

rodentchronic painbehaviourotherhistology molecular

Abstract

Non-invasive treatment methods for neuropathic pain are lacking. We assess how modulatory low intensity focused ultrasound (liFUS) at the L5 dorsal root ganglion (DRG) affects behavioral responses and sensory nerve action potentials (SNAPs) in a common peroneal nerve injury (CPNI) model. Rats were assessed for mechanical and thermal responses using Von Frey filaments (VFF) and the hot plate test (HPT) following CPNI surgery. Testing was repeated 24 h after liFUS treatment. Significant increases in mechanical and thermal sensory thresholds were seen post-liFUS treatment, indicating a reduction in sensitivity to pain (p < 0.0001, p = 0.02, respectively). Animals who received CPNI surgery had significant increases in SNAP latencies compared to sham CPNI surgery animals (p = 0.0003) before liFUS treatment. LiFUS induced significant reductions in SNAP latency in both CPNI liFUS and sham CPNI liFUS cohorts, for up to 35 min post treatment. No changes were seen in SNAP amplitude and there was no evidence of neuronal degeneration 24 h after liFUS treatment, showing that liFUS did not damage the tissue being modulated. This is the first in vivo study of the impact of liFUS on peripheral nerve electrophysiology in a model of chronic pain. This study demonstrates the effects of liFUS on peripheral nerve electrophysiology in vivo. We found that external liFUS treatment results in transient decreased latency in common peroneal nerve (CPN) sensory nerve action potentials (SNAPs) with no change in signal amplitude.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects8, 5swept animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsbehaviour, other, histology molecular — Von Frey filaments; hot plate test; common peroneal nerve sensory nerve action potential latency and amplitude; H&E and FluoroJade-B staining of L5 DRG
Direction of effectmixed or unclearExternal liFUS at the L5 DRG raised mechanical and thermal nociceptive thresholds in CPNI rats at 24 h and transiently shortened SNAP latency (up to about 30 min) in both CPNI and sham-CPNI rats, with no change in SNAP amplitude.
Adverse eventsnone observedH&E and FluoroJade staining of L5 DRG 24 h after liFUS showed no pyknosis, oedema or significant neuronal degeneration.

Exposures

Exposure 1: external liFUS to L5 DRG

Target: dorsal root ganglion — “L5 dorsal root ganglion (DRG)”
Device: other named manufacturer · Acoustic Medical Systems · TheraVision ultrasound system and ultrasonic therapy transducer probe ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)11,000✓✓✓
Pulse duration (ms)13✓✓✓⚑
Pulse repetition frequency (Hz)38✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 49.4%
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

liFUS was administered at 8 W for 3 min with 11 MHz pulsed at 38 Hz with a period of 90 ns, and a pulse width of 13 ms. SNAP recordings occurred concurrently with liFUS or sham treatment; behavioural testing repeated 24 h later.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Text gives a 13 ms pulse width and a 38 Hz PRF together with a 'period of 90 ns'; the three are not mutually consistent. Recorded as written.
  • n_subjects — Total never stated; group sizes from the Fig. 3 legend (CPNI liFUS 8, CPNI shamliFUS 6, sham CPNI liFUS 5, sham CPNI shamliFUS 4). Fig. 5 legend gives 13 CPNI and 9 sham animals, and the text gives n=12 and n=8, so counts differ between places.
  • exposures[0].free_field — Paper gives power (8 W) only; no pressure or intensity.
  • exposures[0].target — DRG treated percutaneously using external landmarks; a peripheral target, not CNS.