Low-intensity low-frequency pulsed ultrasound ameliorates sciatic nerve dysfunction in a rat model of cisplatin-induced peripheral neuropathy
Busra Bilir-Yildiz, Fatma Bahar Sunay, Hatice Fulya Yilmaz, Ozlem Bozkurt-Girit
Scientific Reports 2022 · 10.1038/s41598-022-11978-z
Abstract
Chemotherapy-induced peripheral neuropathy is a neurological complication that frequently occurs during chemotherapeutic intervention, resulting in damaged myelin sheath, motor weakness and/or sensory impairment. This study aims to investigate the therapeutic efficiency of low-intensity pulsed low-frequency ultrasound on cisplatin-induced peripheral neuropathy. Rats were randomly divided into five experimental groups as control, cisplatin administration, 10 mg/kg melatonin treatment after cisplatin administration, 1 MHz frequency 0.5 W/cm 2 pulsed ultrasound treatment after cisplatin administration and 1 MHz frequency 1.5 W/cm 2 pulsed ultrasound treatment after cisplatin administration. Chemical neuropathy was induced by the injection of 3 mg/kg/week of cisplatin (i.p.) for 5 weeks. Afterwards, melatonin and pulsed ultrasound treatments were applied for 15 consecutive days. Cisplatin administration resulted in a decrease in nociceptive pain perception and nerve conduction velocities together with a decrease in myelin thickness and diameters of axons and myelinated fibers, indicating a dysfunction and degeneration in sciatic nerves. In addition, cisplatin administration led to a decrease, in superoxide dismutase activity, and an increase in malondialdehyde and IL-1β levels together with an increase in caspase-3 protein expression levels and a decrease in Bcl-2 and Parkin levels. The ultrasound treatments resulted in an increase in nociceptive pain perception and sciatic nerve conduction; led to a decrease in oxidative stress and inflammation, restored nerve degeneration and regulated apoptosis and mitophagy. Taken together, low-intensity pulsed low-frequency ultrasound was efficient in restoring the alterations attributable to cisplatin-induced peripheral neuropathy, and warrants further investigations.
Abstract via europepmc.
Exposures
Exposure 1: CP + US (0.5 and 1.5 W/cm2), sciatic nerve
Target: sciatic nerve — “approximately 5 cm2 skin area above the sciatic nerve on the lateral thigh of each leg”
Device: other named manufacturer · BTL Medical Technologies · BTL5710 SONO ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 180 | ✓✓✓⚑ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.5, 1.5swept | ✓?⚑ |
US applied for 3 min onto an approximately 5 cm2 skin area above the sciatic nerve of each leg (both legs), at 1 MHz and 0.5 or 1.5 W/cm2 in a pulsed mode at 20% duty cycle, for 15 consecutive days; rats restrained in prone position.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Paper gives only 'power density' of 0.5 and 1.5 W/cm2; whether this is Isppa or Ispta, and in what medium, is not stated. Placed under ispta by choice; treat as metric unknown.exposures[0].timing.pulse_duration_ms— Pulse duration and PRF not stated; only 20% duty cycle.exposures[0].timing.sonication_duration_s— 3 min per leg per day; the 3 min is the restraint and application time, per-leg split not stated.n_subjects— Only group sizes of the two US groups stated (10 each); total not given.exposures[0].device.family— Therapeutic physiotherapy device, not a TUS neuromodulation system; peripheral nerve treatment of neuropathy.sham_type— Paper states no US-applied sham or control groups were included.