Systematic test of neurotoxin dose and volume on muscle function in a rat model.
BACKGROUND
Onabotulinum toxin serotype A (BT-A) is used for a variety of motor and sensory disorders related to abnormal muscle activity.


METHODS
We developed a high-resolution rodent model to allow precise determination of the effect of BT-A dose (measured in units) and injectate volume (measured in μl) on the efficacy of the injection and systemic side effects. Dorsiflexion is the best indicator of injected and contralateral muscle function.


RESULTS
One month after injection, dorsiflexion torque of BT-A-injected limbs was decreased significantly in all experimental groups compared with saline controls (P < 0.05). Torque was also compared among the BT-A groups, which demonstrated a significant effect of dose (P < 0.001), but no effect of volume (P > 0.2) and no dose × volume interaction (P > 0.3). Similar results were observed for other parameters measured.


CONCLUSIONS
These data demonstrate that injection dose and not volume or concentration is the primary determinant of neurotoxin efficacy in a rodent model.
Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, 9500 Gilman Drive, MC0863, La Jolla, California, 92093-0863, USA.
Jonah B
JB
Hulst
Viviane B
VB
Minamoto
Michael B
MB
Lim
Shannon N
SN
Bremner
Samuel R
SR
Ward
Richard L
RL
Lieber
D000704:Analysis of Variance; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D003094:Collagen / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D019415:Torque
D009465:Neuromuscular Agents; D003094:Collagen; D019274:Botulinum Toxins, Type A
Onabotulinum toxin; cerebral palsy; fibrosis; myopathy; spasticity