- • Botulinum neurototoxin type A (BoNT-A) is known to block central synapses after muscular injection due to retrograde transport in animal models.
- • BoNT-A-induced changes in the human CNS activity have been attributed so far to indirect mechanisms involving peripheral afferent inputs modified after muscular injection.
- • The question of a possible direct central action of BoNT-A in humans was further addressed by investigating the modification of spinal recurrent inhibition in stroke patients after BoNT-A muscular injection.
- • Recurrent inhibition from soleus motor axons to motoneurones supplying quadriceps was depressed after BoNT-A injection in ankle plantarflexors.
- • BoNT-A, through retrograde transport, affects spinal synaptic transmission in humans.
Abstract The natural target of the botulinum neurototoxin type A (BoNT-A) is the neuromuscular junction. When injected into a muscle, BoNT-A is internalized by motoneurone terminals where it functions as an endopeptidase, cleaving protein components of the synaptic machinery responsible for vesicle docking and exocytosis. As a result, BoNT-A induces a characteristic flaccid paralysis of the affected muscle. In animal models, BoNT-A applied in the periphery can also influence central activity via retrograde transport and transcytosis. An analogous direct central effect in humans is still debated. The present study was designed to address whether BoNT-A modifies the activity of the spinal recurrent inhibitory pathways, when injected at muscular level, in humans. To avoid methodological bias, the recurrent inhibition from an injected muscle (soleus) was investigated on an untreated muscle (quadriceps), and stimulation parameters (producing recurrent inhibition) were monitored on a third non-injected muscle but innervated by the same nerve as the soleus (flexor digitorum brevis). The experiments were performed on 14 post-stroke patients exhibiting spasticity in ankle plantarflexors, candidates for BoNT-A. One month after BoNT-A, the level of recurrent inhibition was depressed. It is suggested that the depression of recurrent inhibition was induced by BoNT-A, injected peripherally, through axonal transport and blockade of the cholinergic synapse between motoneurone recurrent collaterals and Renshaw cells.