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Analgesic Effects of Transcutaneous Ultrasound Nerve Stimulation in a Rat Model of Oxaliplatin-Induced Mechanical Hyperalgesia and Cold Allodynia

Yueh-Ling Hsieh, Han-Yu Chen, Ching-Hsiang Yang, Chen-Chia Yang

Ultrasound in Medicine & Biology 2017 · 10.1016/j.ultrasmedbio.2017.03.002

rodentchronic painbehaviourhistology molecular

Abstract

This study investigated the effects and underlying mechanisms of therapeutic ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy. Animals received a total of eight injections with oxaliplatin (4 mg/kg), administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm 2 ) started on the fifth oxaliplatin administration and continued for 10 consecutive d. Sensory behavioral examinations, protein levels of transient receptor potential channels (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal dorsal horn were examined. Results indicated that TUS can reduce mechanical and cold hyper-responsive behaviors caused by repeated administration of oxaliplatin. Oxaliplatin-related increases in protein levels of TRPM8 in DRG and SP in the dorsal horn were also reduced after TUS. Taken together, the results revealed beneficial effects of TUS on oxaliplatin-induced mechanical hyperalgesia and cold allodynia and suggested involvement of TUS biochemicals in suppressing TRPM8 in DRG and SP in spinal cords.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects6, 6swept animals
Sessions per subject10
Randomisedyes
Blindingsingle
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutsbehaviour, histology molecularvon Frey mechanical paw-withdrawal threshold; acetone and cold-water immersion withdrawal latency; menthol/capsaicin-evoked nocifensive response duration; Western blot for TRPM8/TRPV1 in DRG; immunohistochemistry for substance P in spinal dorsal horn
Direction of effectinhibitoryTUS reduced oxaliplatin-induced mechanical hyperalgesia and cold allodynia (increased paw withdrawal threshold/latency) and reduced oxaliplatin-related increases in TRPM8 protein in DRG and substance P in the spinal dorsal horn, versus sham-TUS.
Adverse eventsnot reported

Exposures

Exposure 1: Transcutaneous TUS to bilateral hindlimb (sural/peroneal nerve distribution)

Target: peroneal nerve, peripheral nerve — “bilateral hindlimbs innervated by sural and peroneal nerves
Device: other named manufacturer · ITO Co, Tokyo, Japan · US-750

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓
Pulse duration (ms)2✓✓
Pulse repetition frequency (Hz)250?
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)300✓✓
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

Pulsed-mode TUS (1 MHz, ISATA = 0.5 W/cm2, 50% duty cycle) was applied for 5 min per session, one session per day for 10 consecutive days (days 13-22), by slowly moving the sound head in a small circular direction on the bilateral hindlimbs innervated by sural and peroneal nerves.

Flags from extraction

  • n_subjectsStudy had 24 animals in 4 groups of 6; n_subjects here counts only the two groups receiving real TUS (Oxa-TUS, Veh-TUS = 12); the other 12 received sham TUS with device output set to zero.
  • exposures[0].unspecified_domain.ispta_w_cm2Paper gives ISATA (0.5 W/cm2) as a device setting without stating whether it is a free-field/water-tank calibration or an in-tissue value, so placed in unspecified_domain.
  • exposures[0].timing.pulse_repetition_frequency_hzPRF (250 Hz) computed as the reciprocal of the stated 2 ms on / 2 ms off cycle period; the paper does not itself use the term PRF.
  • blindingPaper states the behavioural tester was blinded to the oxaliplatin-vs-vehicle drug condition; it does not explicitly say whether the tester (or TUS administrator) was blinded to TUS-vs-sham-TUS assignment.
  • target.termsSural nerve has no dedicated vocabulary id; represented via the parent peripheral_nerve term alongside the more specific peroneal_nerve.