Botulinum toxin type-A (BTX-A) injections have become a common treatment modality for a variety of neuromuscular disorders with the primary aim to relax spastic muscles, for example, in children with cerebral palsy, or following a stroke. Once injected, BTX-A prevents acetylcholine release at the motor nerve endings, thereby producing a dose-dependent muscle paralysis. Despite an exponential growth of patients receiving BTX-A treatment, there has been no systematic evaluation of the effects of the toxin on target and non-target muscles. Therefore, the general purpose of this PhD project was to evaluate muscle mass, strength, and contractile material in injected and contralateral non-injected quadriceps muscles of New Zealand White (NZW) rabbits following single and repeated BTX-A injections. Muscle mass was assessed as the wet weight of muscles following sacrifice, strength was assessed by stimulating the knee extensor muscles via femoral nerve stimulation and quantifying the knee extensor force, the amount of contractile material was quantified histologically.

We found that six-monthly BTX-A injections into the quadriceps caused substantial muscle weakness, atrophy, and contractile material loss in the injected and the contralateral non-injected muscles. Adding direct electrical muscle stimulation during the BTX-A injection help to alleviate muscle mass, strength and contractile material loss and the injected and contralateralnon injected muscles, and finally, BTX-A injections had long lasting effects that were not fully recovered at six months following the end of the injection protocol.

We concluded from the results of this series of studies that BTX-A treatment resulted in adverse effects on the injected and contralateral non-injected musculature up to six months following the injection protocol. Future studies should be aimed at identifying strategies that minimize/prevent adverse effects of BTX-A injections on target and non-target muscles.