Systematic test of neurotoxin dose and volume on muscle function in a rat model

Introduction: 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.