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

Authors

  • Jonah B. Hulst MD,

    1. Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, La Jolla, California, USA
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  • Viviane B. Minamoto PT, PhD,

    1. Department of Radiology, University of California San Diego, San Diego, California, USA
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  • Michael B. Lim MD,

    1. Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, La Jolla, California, USA
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  • Shannon N. Bremner BS,

    1. Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, La Jolla, California, USA
    2. Veterans Affairs San Diego Healthcare System, San Diego, California, USA
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  • Samuel R. Ward PT, PhD,

    1. Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, La Jolla, California, USA
    2. Department of Radiology, University of California San Diego, San Diego, California, USA
    3. Veterans Affairs San Diego Healthcare System, San Diego, California, USA
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  • Richard L. Lieber PhD

    Corresponding author
    1. Departments of Orthopaedic Surgery and Bioengineering, University of California San Diego, La Jolla, California, USA
    2. Department of Radiology, University of California San Diego, San Diego, California, USA
    3. Veterans Affairs San Diego Healthcare System, San Diego, California, USA
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  • Funding for this study was provided by the Department of Veterans Affairs Grant RX000670, NIH grants R24HD050837 and AR057013, and Allergan, Inc.

  • This work was presented, in part, at the Tetraplegia Hand meeting in Paris, September 10–12, 2010, as well as the American Academy of Cerebral Palsy and Developmental Medicine and Child Neurology in Toronto, September 12–14, 2012.

ABSTRACT

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. Muscle Nerve 49: 709–715, 2014

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