Botox produces functional weakness in non-injected muscles adjacent to the target muscle

Abstract

Botulinum type-A (BTX-A) neurotoxin exerts a paralytic effect on muscles and is used increasingly to treat a variety of muscle spasticity disorders. While its pathogenesis for muscle-induced weakness has been well elucidated, the functional effects of BTX-A administration are incomplete. Specifically, weakness as a function of muscle length and stimulation frequency has only been investigated qualitatively in a few muscles and the possible effect of the toxin on non-target muscles, although considered possible based on laboratory experiments, has not been studied widely and the functional implications remain unknown. Therefore, the purpose of this study was to measure the functional implications of BTX-A on force production and possible weakness of a target muscle and a non-injected neighbouring muscle. The cat soleus was chosen as the target muscle and was injected with 3.2-3.5U of BTX-A/kg in one hind limb, while the soleus of the other hind limb served as a non-injected control. Force-length properties within and exceeding the functional range of motion were determined at frequencies of stimulation of 10, 30 and 50Hz. Force-length properties of the adjacent non-injected plantaris were also determined in the experimental and contralateral hind limb. Four weeks following BTX-A injections, peak soleus forces were decreased by 30% (50Hz), 29% (30Hz) and 29% (10Hz) and peak plantaris forces were decreased by 11% (50Hz), 16% (30Hz) and 16% (10Hz), in the experimental compared to the contralateral hind limb. Absolute BTX-associated force loss was significantly different at all frequencies of stimulation and all lengths for the soleus, while in the plantaris there was a significant force loss across long (> or = -4mm) but not short muscle lengths. Decreases in peak force were independent of the stimulation frequency. We concluded from the results of this study that BTX-A injection in the target muscle caused a measurable effect on force production and that force production was decreased in non-target neighbouring muscles at and near lengths of peak force production. These results are of particular importance in therapeutic procedures where isolated muscles are targeted for treatment. They should also be considered in neurophysiological studies in which BTX-A injections are used to selectively diminish muscle function.