title: Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.
abstract: BACKGROUND
  Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months.
  
  
  METHODS
  Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8).
  
  
  RESULTS
  The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping.
  
  
  CONCLUSIONS
  These experiments demonstrate a disproportionately greater effect of repeated BoNT injections.
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA.
authors.forename: Viviane B
authors.initials: VB
authors.lastname: Minamoto
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA.
authors.forename: Kentaro P
authors.initials: KP
authors.lastname: Suzuki
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Bremner
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA.|Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.|Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA.|Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.|Department of Radiology, University of California San Diego, La Jolla, California, USA.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004334:Drug Administration Schedule; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D007273:Injections, Intramuscular; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009465:Neuromuscular Agents / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D009465:Neuromuscular Agents; D020033:Protein Isoforms; D003094:Collagen; D019274:Botulinum Toxins, Type A; D018995:Myosin Heavy Chains
keywords: Botox®; denervation; fiber type; muscle physiology; neurotoxin