Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics
Thomas Anthony Anderson, Jorge Delgado, Sharon Sun, Negin Behzadian, Jose Vilches-Moure, Robert B Szlavik, Kim Butts-Pauly, David Yeomans
Regional Anesthesia & Pain Medicine 2022 · 10.1136/rapm-2021-103115
Abstract
Background In animal models, focused ultrasound can reversibly or permanently inhibit nerve conduction, suggesting a potential role in managing pain. We hypothesized focused ultrasound's effects on action potential parameters may be similar to those of local anesthetics. Methods In an ex vivo rat sciatic nerve model, action potential amplitude, area under the curve, latency to 10% peak, latency to 100% peak, rate of rise, and half peak width changes were assessed after separately applying increasing focused ultrasound pressures or concentrations of bupivacaine and ropivacaine. Focused ultrasound's effects on nerve structure were examined histologically. Results Increasing focused ultrasound pressures decreased action potential amplitude, area under the curve, and rate of rise, increased latency to 10% peak, and did not change latency to 100% peak or half peak width. Increasing local anesthetic concentrations decreased action potential amplitude, area under the curve, and rate of rise and increased latency to 10% peak, latency to 100% peak, and half peak width. At the highest focused ultrasound pressures, nerve architecture was altered compared with controls. Discussion While some action potential parameters were altered comparably by focused ultrasound and local anesthetics, there were small but notable differences. It is not evident if these differences may lead to differences in clinical pain effects when focused ultrasound is applied in vivo or if focused ultrasound pressures that result in clinically relevant changes damage nerve structures. Given the potential advantages of a non-invasive technique for managing pain conditions, further investigation may be warranted in an in vivo pain model.
Abstract via europepmc.
Exposures
Exposure 1: HIFU of ex vivo rat sciatic nerve in a bath
Target: excised nerve, sciatic nerve — “ex vivo rat sciatic nerve”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,470 | ✓✓✓ |
| Pulse duration (ms) | 25 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 15 | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 1,300, 2,870swept | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 52, 255.5swept | ✓✓✓⚑ |
Pulse train of 25 ms on and 25 ms off (duty cycle 50%) applied for 15 s; HIFU reapplied every 2 min at pressures increasing in 0.11 MPa increments from 1.30 MPa until the CAP amplitude fell to zero; CAPs recorded 30 and 90 s after the start of each application.
Flags from extraction
exposures[0].free_field.pressure_kpa— Initial pressure stated as peak-to-peak (1.30 MPa); the 1.30 to 2.87 MPa range is not labelled as peak-to-peak or peak negative; paper says pressures were measured during transducer calibration with a fiber optic hydrophoneexposures[0].unspecified_domain.ispta_w_cm2— Ispta given as corresponding to pressures; paper says intensities are estimates based on assumed nerve acoustic impedancen_subjects— HIFU experiments used 26 nerves from 18 rats; a separate histology cohort of 20 nerves from 10 rats included 'low HIFU' and 'high HIFU' arms; recorded 26 preparationsexposures[0].timing.pulse_repetition_frequency_hz— PRF not stated; only 25 ms on / 25 ms off givenexposures[0].device.family— Transducer maker not named; hydrophone (Precision Acoustics) is not the transducer