title: Dose- and volume dependent-response to intramuscular injection of botulinum neurotoxin-A optimizes muscle force decrement in mice.
abstract: Botulinum neurotoxin-A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n = 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 µl) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 µl). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post-injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 µl injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone.
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. ausstone@wfubmc.edu
authors.forename: Austin V
authors.initials: AV
authors.lastname: Stone
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.forename: Michael F
authors.initials: MF
authors.lastname: Callahan
authors.forename: Beth P
authors.initials: BP
authors.lastname: Smith
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Garrett
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Smith
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Koman
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A