Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A

J Physiol. 2013 Feb 15;591(4):1017-29. doi: 10.1113/jphysiol.2012.239178. Epub 2012 Oct 8.


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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Botulinum Toxins, Type A / pharmacology*
  • Female
  • Femoral Nerve / drug effects
  • Femoral Nerve / physiology
  • H-Reflex / drug effects
  • Humans
  • Male
  • Middle Aged
  • Motor Neurons / drug effects
  • Motor Neurons / physiology
  • Muscle Spasticity / drug therapy*
  • Muscle Spasticity / physiopathology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Stroke / complications
  • Stroke / physiopathology
  • Tibial Nerve / drug effects
  • Tibial Nerve / physiology


  • Botulinum Toxins, Type A
  • incobotulinumtoxinA