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Original research
Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain
  1. Thomas Anthony Anderson1,
  2. Cholawat Pacharinsak2,
  3. Jose Vilches-Moure2,
  4. Husniye Kantarci3,
  5. J Bradley Zuchero3,
  6. Kim Butts-Pauly4 and
  7. David Yeomans1
  1. 1Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA
  2. 2Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA
  3. 3Neurosurgery, Stanford University School of Medicine, Stanford, California, USA
  4. 4Radiology, Stanford University School of Medicine, Stanford, California, USA
  1. Correspondence to Dr Thomas Anthony Anderson, Anesthesiology, Perioperative and Pain Medicine, Stanford Medicine, Stanford, CA 94305, USA; tanders0{at}stanford.edu

Abstract

Background Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound’s effects on behavior and peripheral nerve structure.

Methods Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy.

Results Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy.

Discussion Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

  • nerve block
  • pain, postoperative
  • regional anesthesia
  • acute pain
  • pain management

Data availability statement

Data are available on reasonable request.

https://doi.org/10.1136/rapm-2022-104060

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Correction notice This article has been corrected since it published Online First. The figure 3 legend has been corrected.

    • Contributors CP, JV-M, HK and JBZ: This author helped with data analysis, data interpretation, writing and final approval of the manuscript. KB-P and DY: This author helped with research conceptualization, data interpretation, writing and final approval of the manuscript. TAA: This author helped with research conceptualization and design, data collection, data analysis, data interpretation, writing and final approval of the manuscript and is the author acting as guarantor.

    • Funding TAA received funding from a Foundation for Anesthesia Education and Research Mentored Research Training Grant (Washington D.C.). DY is supported by DOD CDMRP grant 13113162, NIH grant UG3NS11563701, and NIH grant R21NS08884102. JBZ is supported by NIH grant R01NS119823.

    • Disclaimer This manuscript’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or the National Institutes of Health.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.