Skip to main content
SpringerLink
Log in
Book cover

Pathophysiology and Surgical Treatment of Unilateral Vocal Fold Paralysis pp 45–88Cite as

Denervation and Reinnervation of the Thyroarytenoid Muscle

  • Chapter

  • 827 Accesses

Abstract

The detailed effects of denervation on the intrinsic laryngeal muscles of rats were investigated. After denervation, the entire thyroarytenoid (TA) muscle and individual muscle fibers thereof gradually reduced in size over the next 10 weeks, but unlike muscles of the extremities, the dimensions then remained unchanged to 58 weeks of observation. Although nerve terminals disappeared within 24 h of nerve transection, approximately 70 % of the acetylcholine receptors (AchRs) were preserved at 10 weeks post-denervation. Subsequently, AchR numbers gradually decreased to 35 % of the initial value by 58 weeks after denervation. Nerve–muscle pedicle (NMP) flap implantation into the denervated TA muscle facilitated recovery of bulk muscle size, individual muscle fibers, neuromuscular junctions (NMJs), and function as reflected by evoked electromyography (EMG) testing. Such positive effects were noted even when the NMP procedure was performed 48 weeks post-injury, although treatment effects were less prominent as the time to treatment became extended. The NMP method also yielded favorable results in aged rats and animals in which the TA muscle became partially reinnervated after nerve injury.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Midrio M. The denervated muscle: facts and hypotheses. A historical review. Eur J Appl Physiol. 2006;98:1–21.

    Article  PubMed  Google Scholar 

  2. Schmalbruch H, Al-Amood WS, Lewis DM. Morphology of long-term denervated rat soleus muscle and the effect of chronic electrical stimulation. J Physiol. 1991;441:243–56.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Viguie CA, Lu DX, Huang SK, et al. Quantitative study of the effects of long-term denervation on the extensor digitorum longus muscle of the rat. Anat Rec. 1997;248:346–54.

    Article  CAS  PubMed  Google Scholar 

  4. Shindo ML, Herzon GD, Hanson DG, Cain DJ, Sahgal V. Effects of denervation on laryngeal muscles: a canine model. Laryngoscope. 1992;102:663–9.

    Article  CAS  PubMed  Google Scholar 

  5. Shinners MJ, Goding GS, McLoon LK. Effect of recurrent laryngeal nerve section on the laryngeal muscles of adult rabbits. Otolaryngol Head Neck Surg. 2006;134:413–8.

    Article  PubMed  Google Scholar 

  6. Winlow W, Usherwood PN. Ultrastructural studies of normal and degenerating mouse neuromuscular junctions. J Neurocytol. 1975;4:377–94.

    Article  CAS  PubMed  Google Scholar 

  7. Frank E, Gautvik K, Sommerschild H. Persistence of junctional acetylcholine receptors following denervation. Cold Spring Harb Symp Quant Biol. 1976;40:275–81.

    Article  CAS  PubMed  Google Scholar 

  8. Andreose JS, Fumagalli G, Lomo T. Number of junctional acetylcholine receptors: control by neural and muscular influence in the rat. J Physiol. 1995;483:397–406.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Portillo F, Pasaro R. Location of motoneurons supplying the intrinsic laryngeal muscles of rats. Horseradish peroxidase and fluorescence double-labeling study. Brain Behav Evol. 1988;32:220–5.

    Article  CAS  PubMed  Google Scholar 

  10. Lobera B, Pasaro R, Gonzalez-Baron S, Delgado-Garcia JM. A morphological study of ambiguus nucleus motoneurons innervating the laryngeal muscles in the rat and cat. Neurosci Lett. 1981;23:125–30.

    Article  CAS  PubMed  Google Scholar 

  11. Yoshida Y, Yatake K, Tanaka Y, et al. Morphological observation of laryngeal motoneurons by means of cholera toxin B subunit tracing technique. Acta Otolaryngol. 1998;118 Suppl 539:98–105.

    Article  Google Scholar 

  12. Komori M. Effects of neurotrophic factors on regeneration of denervated recurrent laryngeal nerve in the rat. Pract Otorhinolaryngol. 1999;92:677–86. (in Japanese)

    Google Scholar 

  13. Sanuki T, Yumoto E, Komori M, Hyodo M. Expression of fibroblast growth factor-2 in the nucleus ambiguus following recurrent laryngeal nerve injury in the rat. Laryngoscope. 2000;110:2128–34.

    Article  CAS  PubMed  Google Scholar 

  14. Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain. 1951;74:491–516.

    Article  CAS  PubMed  Google Scholar 

  15. Huber K, Meisinger C, Grotiie C. Expression of fibroblast growth factor-2 in hypoglossal motoneurons is stimulated by peripheral nerve injury. J Comp Neurol. 1997;382:189–98.

    Article  CAS  PubMed  Google Scholar 

  16. Fujimoto E, Mizoguchi A, Hanada K, Yajima M, Ide C. Basic fibroblast growth factor promotes extension of regenerating axons of peripheral nerve. In vivo experiments using a Schwann cell basal lamina tube model. J Neurocytol. 1997;26:511–28.

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi J, Mackinnon SE, Watanabe O, Ball DJ, Gu XM, Hunter DA, Kuzon Jr WM. The effect of duration of muscle denervation on functional recovery in the rat model. Muscle Nerve. 1997;20:858–66.

    Article  CAS  PubMed  Google Scholar 

  18. Johns MM, Urbanchek M, Chepeha DB, Kuzon Jr WM, Hogikyan ND. Thyroarytenoid muscle maintains normal contractile force in chronic vocal fold immobility. Laryngoscope. 2001;111:2152–6.

    Article  CAS  PubMed  Google Scholar 

  19. Kirchner JA. Atrophy of laryngeal muscles in vagal paralysis. Laryngoscope. 1966;76:1753–65.

    Article  CAS  PubMed  Google Scholar 

  20. Kirchner JA. Intrathoracic injury to the motor nerve supply of the larynx. Acta Otolaryngol. 1977;83:163–9.

    Article  CAS  PubMed  Google Scholar 

  21. Kawakita S, Aibara R, Kawamura Y, Yumoto E, Desaki J. Motor innervation of the guinea pig interarytenoid muscle: reinnervation process following unilateral denervation. Laryngoscope. 1998;108:398–402.

    Article  CAS  PubMed  Google Scholar 

  22. Gacek M, Gacek RR. Cricoarytenoid joint mobility after chronic vocal cord paralysis. Laryngoscope. 1996;106:1528–30.

    Article  CAS  PubMed  Google Scholar 

  23. Müller A, Paulsen FP. Impact of vocal cord paralysis on cricoarytenoid joint. Ann Otol Rhinol Laryngol. 2002;111:896–901.

    Article  PubMed  Google Scholar 

  24. Brown MC, Holland RL, Hopkins WG. Motor nerve sprouting. Ann Rev Neurosci. 1981;4:17–42.

    Article  CAS  PubMed  Google Scholar 

  25. Miyauchi A, Matsusaka K, Kihara M, Matsuzuka F, Hirai K, Yokozawa T, Kobayashi A, Kuma K. The role of ansa-to-recurrent laryngeal nerve anastomosis in operations for thyroid cancer. Eur J Surg. 1998;164:927–33.

    Article  CAS  PubMed  Google Scholar 

  26. Miyauchi A, Inoue H, Tomoda C, Fukushima M, Kihara M, Higashiyama T, Takamura Y, Ito Y, Kobayashi K, Miya A. Improvement in phonation after reconstruction of the recurrent laryngeal nerve in patients with thyroid cancer invading the nerve. Surgery. 2009;146:1056–62.

    Article  PubMed  Google Scholar 

  27. Yumoto E, Sanuki T, Kumai Y. Immediate recurrent laryngeal nerve reconstruction and vocal outcome. Laryngoscope. 2006;116:1657–61.

    Article  PubMed  Google Scholar 

  28. Sanuki T, Yumoto E, Minoda R, Kodama N. The role of immediate recurrent laryngeal nerve reconstruction for thyroid cancer surgery. J Oncol. 2010;2010:846235.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Aitken JT. Problems of reinnervation of muscle. Prog Brain Res. 1965;14:232–62.

    Article  CAS  PubMed  Google Scholar 

  30. Anzil AP, Wernig A. Muscle fibre loss and reinnervation after long-term denervation. J Neurocytol. 1989;18:833–45.

    Article  CAS  PubMed  Google Scholar 

  31. Su WF, Hsu YD, Chen HC, Sheng H. Laryngeal reinnervation by ansa cervicalis nerve implantation for unilateral vocal cord paralysis in humans. J Am Coll Surg. 2007;204:64–72.

    Article  PubMed  Google Scholar 

  32. Frey M, Gruber H, Holle J, Freilinger G. An experimental comparison of the different kinds of muscle reinnervation: nerve suture, nerve implantation, and muscular neurotization. Plast Reconstr Surg. 1982;69:656–67.

    Article  CAS  PubMed  Google Scholar 

  33. Cedars MG, Miller TA. A review of free muscle grafting. Plast Reconstr Surg. 1984;74:712–20.

    Article  CAS  PubMed  Google Scholar 

  34. Hogikyan ND, Johns MM, Kileny PR, Urbanchek M, Carroll WR, Kuzon WM. Motion-specific laryngeal reinnervation using muscle-nerve-muscle neurotization. Ann Otol Rhinol Laryngol. 2001;110:801–10.

    Article  CAS  PubMed  Google Scholar 

  35. Debnath I, Rich JT, Paniello RC. Intrinsic laryngeal muscle reinnervation using muscle-nerve-muscle technique. Ann Otol Rhinol Laryngol. 2008;117:382–8.

    Article  PubMed  Google Scholar 

  36. Sato F, Ogura JH. Functional restoration for recurrent laryngeal paralysis: an experimental study. Laryngoscope. 1978;88:855–71.

    Article  CAS  PubMed  Google Scholar 

  37. Meikle D, Trachy RE, Cummings CW. Reinnervation of skeletal muscle: a comparison of nerve implantation with neuromuscular pedicle transfer in an animal model. Ann Otol Rhinol Laryngol. 1987;96:152–7.

    Article  CAS  PubMed  Google Scholar 

  38. Tucker HM. Reinnervation of the unilaterally paralyzed larynx. Ann Otol Rhinol Laryngol. 1977;86:789–94.

    Article  CAS  PubMed  Google Scholar 

  39. Tucker HM, Rusnov M. Laryngeal reinnervation for unilateral vocal cord paralysis: long-term results. Ann Otol Rhinol Laryngol. 1981;90:457–9.

    Article  CAS  PubMed  Google Scholar 

  40. May M, Beery Q. Muscle-nerve pedicle laryngeal reinnervation. Laryngoscope. 1986;96:1196–200.

    CAS  PubMed  Google Scholar 

  41. Zheng H, Zhou S, Chen S, Li Z, Cuan Y. An experimental comparison of different kinds of laryngeal muscle reinnervation. Otolaryngol Head Neck Surg. 1998;119:540–7.

    Article  CAS  PubMed  Google Scholar 

  42. Sayers H, Tonge DA. A study of factors influencing synapse formation by a foreign nerve in skeletal muscleof Rana pipiens. J Physiol Lond. 1986;375:449–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Aoyama T, Kumai Y, Yumoto E, Ito T, Miyamaru S, Sanuki T. Effects of nerve-muscle pedicle on the rat immobile vocal fold in the presence of partial innervations. Ann Otol Rhinol Laryngol. 2010;119:823–9.

    Article  PubMed  Google Scholar 

  44. Dupont-Versteegden EE, Houle JD, Gureley CM, Peterson CA. Early changes in the muscle fiber size and gene expression in response to spinal cord transection and exercise. Am J Physiol. 1998;275:1124–33.

    Google Scholar 

  45. Keilhoff G, Fansa H. Successful intramuscular neurotization is dependent on the denervation period. A histomorphological study of the gracilis muscle in the rats. Muscle Nerve. 2005;31:221–8.

    Article  PubMed  Google Scholar 

  46. Kumai Y, Ito T, Matsukawa A, Yumoto E. Effects of denervation on neuromuscular junctions in the thyroarytenoid muscle. Laryngoscope. 2005;115:1869–72.

    Article  PubMed  Google Scholar 

  47. Widenmann B, Frank WW. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell. 1985;41:1017–28.

    Article  Google Scholar 

  48. Anderson MJ, Cohen MW. Fluorescent staining of acetylcholine receptors in vertebrate skeletal muscle. J Physiol. 1974;237:385–400.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Miyamaru S, Kumai Y, Ito T, Yumoto E. Effects of long-term denervation on the rat thyroarytenoid muscle. Laryngoscope. 2008;118:1318–23.

    Article  PubMed  Google Scholar 

  50. Nomoto M, Yoshihara T, Kanda T, Kaneko T. Synapse formation by autonomic nerves in the previously denervated neuromuscular junctions of the feline intrinsic muscles. Brain Res. 1991;539:276–86.

    Article  CAS  PubMed  Google Scholar 

  51. Dedo HH, Ogura JH. Vocal cord electromyography in the dog. Laryngoscope. 1965;75:201–11.

    Article  CAS  PubMed  Google Scholar 

  52. Tucker HM. Long-term results of nerve-muscle pedicle reinnervation for laryngeal paralysis. Ann Otol Rhinol Laryngol. 1989;98:674–6.

    Article  CAS  PubMed  Google Scholar 

  53. Hengener AS, Tucker HM. Restoration of abduction in the paralyzed canine vocal fold. Arch Otolaryngol. 1973;97:247–50.

    Article  Google Scholar 

  54. Lyons RM, Tucker HM. Delayed restoration of abduction in the paralyzed canine larynx. Arch Otolaryngol. 1974;100:176–9.

    Article  CAS  PubMed  Google Scholar 

  55. Anonsen CK, Patterson HC, Trachy RE, Gordon AM, Cummings CW. Reinnervation of skeletal muscle with a neuromuscular pedicle. Otolaryngol Head Neck Surg. 1985;93:48–57.

    CAS  PubMed  Google Scholar 

  56. Fata JJ, Malmgren LT, Gacek RR, Dum R, Woo P. Histochemical study of posterior cricoarytenoid muscle reinnervation by a nerve-muscle pedicle in the cat. Ann Otol Rhinol Laryngol. 1987;96:479–87.

    Article  CAS  PubMed  Google Scholar 

  57. Rice DH, Owens O, Burstein F, Verity A. The nerve-muscle pedicle. Arch Otolaryngol. 1983;109:233–4.

    Article  CAS  PubMed  Google Scholar 

  58. Crumley RL. Experiments in laryngeal reinnervation. Laryngoscope. 1982;92 Suppl 3:1–27.

    Article  CAS  PubMed  Google Scholar 

  59. Kumai Y, Ito T, Udaka N, Yumoto E. Effects of a nerve-muscle pedicle on the denervated rat thyroarytenoid muscle. Laryngoscope. 2006;116:1027–32.

    Article  PubMed  Google Scholar 

  60. Windidch A, Gundersen K, Szabolcs M, Gruber H, Lømo T. Fast to slow transformation of denervated and electrically stimulated rat muscle. J Physiol. 1998;510:623–32.

    Article  Google Scholar 

  61. Sterne GD, Coulton GR, Brown RA, et al. Neurotrophin-3-enhanced nerve regeneration selectively improves recovery of muscle fibers expressing myosin heavy chains 2b. J Cell Biol. 1997;139:709–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Miyamaru S, Kumai Y, Ito T, Sanuki T, Yumoto E. Nerve-muscle pedicle implantation facilitates re-innervation of long-term denervated thyroarytenoid muscle in rats. Acta Otolaryngol. 2009;129:1486–92.

    Article  PubMed  Google Scholar 

  63. Nguyen QT, Sanes JR, Lichtman JW. Pre-existing pathways promote precise projection patterns. Nat Neurosci. 2002;5:861–7.

    Article  CAS  PubMed  Google Scholar 

  64. Bader D. Reinnervation of motor endplate-containing and motor endplate-less muscle grafts. Dev Biol. 1980;77:315–27.

    Article  CAS  PubMed  Google Scholar 

  65. Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol. 2001;91:534–51.

    CAS  PubMed  Google Scholar 

  66. Miyamaru S, Kumai Y, Minoda R, Yumoto E. Nerve-muscle pedicle implantation in the denervated thyroarytenoid muscle of aged rats. Acta Otolaryngol. 2012;132:210–7.

    Article  PubMed  Google Scholar 

  67. Connor NP, Suzuki T, Lee K, Sewall GK, Heisey DM. Neuromuscular junction changes in aged rat thyroarytenoid muscle. Ann Otol Rhinol Laryngol. 2002;111:579–86.

    Article  PubMed  Google Scholar 

  68. McMullen CA, Andrade FH. Functional and morphological evidence of age-related denervation in rat laryngeal muscles. J Gerontol A Biol Sci Med Sci. 2009;64:435–42.

    Article  PubMed  Google Scholar 

  69. Suzuki T, Connor NP, Lee K, Bless DM, Ford CN, Inagi K. Age-related alterations in myosin heavy chain isoforms in rat intrinsic laryngeal muscle. Ann Otol Rhinol Laryngol. 2002;111:962–7.

    Article  PubMed  Google Scholar 

  70. McMullen CA, Andrade FH. Contractile dysfunction and altered metabolic profile of the aging rat thyroarytenoid muscle. J Appl Physiol. 2006;100:602–8.

    Article  PubMed  Google Scholar 

  71. Malmgren LT, Jones CE, Bookman LM. Muscle fiber and satellite cell apoptosis in the aging human thyroarytenoid muscle: a stereological study with confocal laser scanning microscopy. Otolaryngol Head Neck Surg. 2001;125:34–9.

    Article  CAS  PubMed  Google Scholar 

  72. Mark RF. Selective innervation of muscle. Br Med Bull. 1974;30:122–5.

    CAS  PubMed  Google Scholar 

  73. Kumai Y, Aoyama T, Nishimoto K, Sanuki T, Minoda R, Yumoto E. Recurrent laryngeal nerve regeneration through a silicone tube produces reinnervation without vocal fold mobility in rats. Ann Otol Rhinol Laryngol. 2013;122:49–53.

    Article  PubMed  Google Scholar 

  74. Crumley R. Laryngeal synkinesis revisited. Ann Otol Rhinol Laryngol. 2000;109:365–71.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otlaryngology Head and Neck Surgery, Graduate School of Medical Sciences Kumamoto University, Kumamoto, Japan

    Eiji Yumoto

Authors
  1. Eiji Yumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Yumoto, E. (2015). Denervation and Reinnervation of the Thyroarytenoid Muscle. In: Pathophysiology and Surgical Treatment of Unilateral Vocal Fold Paralysis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55354-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55354-0_3

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55353-3

  • Online ISBN: 978-4-431-55354-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation