10 Jun BOTOX: Mechanism of Action
Since the mathematical proof for the safety of BOTOX or Botulinum toxin A was shown in the previous post ‘Botulinum Toxin,’ we will now delve into the slightly less sexy ‘mechanism of action’ for botulinum toxin. First, a brief anatomy lesson. Skeletal muscles, those attached to bones, are under direct and usually deliberate control of the central nervous system (the brain and spinal cord). The muscles require input from the nerves in order to contract or move. The connection between the nerves and muscles takes place at the neuromuscular junction or motor end plate. Each muscle fiber has only one neuromuscular junction but each nerve can split to many muscle fibers; rule of thumb-the finer the movement, the fewer muscle fibers per nerve (see Figure 1).
Figure 1 shows a terminal nerve fiber or axon as it splits and ends at neuromuscular junctions (motor end plates). Courtesy of Dartmouth.edu.
Now, back to BOTOX, whereas we describe botulinum toxin as ‘softening’ the muscles and is injected either into or next to the muscles, it actually has no direct effect on the muscles. The botulinum toxin does its work in the nerves at the neuromuscular junctions. Normal signal transmission requires the interaction between proteins on acetylcholine containing vesicles and those in the neuron cell membrane (SNARE proteins in Figure 2). This interaction allows the vesicles to merge with the neuron cell membrane releasing acetylcholine into the synaptic cleft thereby signaling the muscle to contract.
Figure 2 shows a graphic representation of the neuromuscular junction and botulinum toxin effects on certain proteins1.
But after an injection of BOTOX (recommended) or ingestion of green beans from a bulging can (not recommended), the vesicle with acetylcholine picks up the botulinum toxin. The botulinum toxin is then brought into the neuron by the vesicle where it splits and runs around reeking havoc. SNARE proteins are cleaved preventing interaction between the vesicles and the cell membrane. BOTOX and Xeomin are both botulinum toxin type A which cleaves the SNAP-25 protein (SNAP = synaptosomal associated protein). No interaction, no acetylcholine release, no muscle contraction leads to softened facial features especially active wrinkles.
After three to four months the nerve recovers. During this time the nerve grows new axonal branches to form new neuromuscular junctions with the muscles.
Thanks for your attention,
Robert Zieber, MD
De Luz Medical Aesthetics
Next: Indications: yes BOTOX can do that…
1. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum Toxin as a Biological Weapon: Medical and Public Health Management. JAMA. 2001;285(8):1059-1070. doi:10.1001/jama.285.8.1059.