TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration

Sci Rep. 2020 Oct 9;10(1):16892. doi: 10.1038/s41598-020-72288-w.

Abstract

Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism
  • Animals
  • Collagen / metabolism
  • Laryngeal Muscles / innervation
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism
  • Motor Neurons / drug effects*
  • Motor Neurons / metabolism
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / metabolism
  • Nerve Regeneration / drug effects*
  • Peripheral Nervous System / drug effects
  • Peripheral Nervous System / metabolism
  • Polyglycolic Acid / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkA / antagonists & inhibitors*
  • Recurrent Laryngeal Nerve / drug effects*
  • Recurrent Laryngeal Nerve / metabolism
  • Recurrent Laryngeal Nerve Injuries / drug therapy*
  • Recurrent Laryngeal Nerve Injuries / metabolism
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / metabolism
  • Vocal Cords / drug effects
  • Vocal Cords / metabolism

Substances

  • Polyglycolic Acid
  • Collagen
  • Receptor, trkA