title: Modulating neuromuscular junction density changes in botulinum toxin-treated orbicularis oculi muscle.
abstract: OBJECTIVE
  Botulinum toxin A is the most commonly used treatment for blepharospasm, hemifacial spasm, and other focal dystonias. Its main drawback is its relatively short duration of effect. The goal of this study was to examine the ability of corticotropin releasing factor (CRF) or antibody to insulin growth factor I-receptor (anti-IGFIR) to reduce the up-regulation of neuromuscular junctions that are associated with return of muscle function after botulinum toxin treatment.
  
  
  METHODS
  Eyelids of adult rabbits were locally injected with either botulinum toxin alone or botulinum toxin treatment followed by injection of either CRF or anti-IGFIR. After one, two, or four weeks, the orbicularis oculi muscles within the treated eyelids were examined for density of neuromuscular junctions histologically.
  
  
  RESULTS
  Injection of botulinum toxin into rabbit eyelids resulted in a significant increase in the density of neuromuscular junctions at one and two weeks, and an even greater increase in neuromuscular junction density by four weeks after treatment. Treatment with either CRF or anti-IGFIR completely prevented this increase in neuromuscular junction density.
  
  
  CONCLUSIONS
  The return of function after botulinum toxin-induced muscle paralysis is due to terminal sprouting and formation of new neuromuscular junctions within the paralyzed muscles. Injection with CRF or anti-IGFIR after botulinum toxin treatment prevents this sprouting, which in turn should increase the duration of effectiveness of single botulinum toxin treatments. Future physiology studies will address this. Prolonging botulinum toxin's clinical efficacy should decrease the number of injections needed for patient muscle spasm relief, decreasing the risk of negative side effects and changes in drug effectiveness that often occurs over a lifetime of botulinum toxin exposure.
authors.affiliation: Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Harrison
authors.forename: Zachary
authors.initials: Z
authors.lastname: Berbos
authors.forename: Renzo A
authors.initials: RA
authors.lastname: Zaldivar
authors.forename: Brian C
authors.initials: BC
authors.lastname: Anderson
authors.forename: Mollie
authors.initials: M
authors.lastname: Semmer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.forename: Linda K
authors.initials: LK
authors.lastname: McLoon
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005143:Eyelids / Q000187:drug effects; D008297:Male; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D017526:Receptor, IGF Type 1 / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D009465:Neuromuscular Agents; D003346:Corticotropin-Releasing Hormone; D017526:Receptor, IGF Type 1; D019274:Botulinum Toxins, Type A