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Chemodenervation From Physiology of the Skin, Third Edition

By: Zoe Draelos, MD, and Peter T. Pugliese, MD
Posted: January 5, 2011, from the January 2011 issue of Skin Inc. magazine.
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Botulinum toxin comes in several different types—A, B, C-1, D, E, F and G. All of the types have the same effect on the junction between the muscle and the nerve, known as the neuromuscular junction. Botulinum toxin functions to prevent the release of acetylcholine, a neurotransmitter that allows the signal from the nerve to be sent to the muscle. When the release of acetylcholine is prevented, the muscle never receives the message to contract and remains at rest. On the forehead, this means that the frown lines do not appear because the muscles do not contract, preventing this facial expression. Because some mature people seem to frown even at rest, resulting in an unattractive facial appearance not consistent with their true inner feelings, botulinum toxin can provide them with a more pleasant, youthful demeanor.

Several types of botulinum toxin have been commercialized. Botulinum toxin A, commercially known as Botox*, was the first approved in the United States and is the most popular today. The second product to be commercialized was botulinum toxin B, commercially known as Myoblock**, but this toxin is no longer used for cosmetic purposes. The third botulinum toxin approved was also a botulinum toxin A, but it had a slightly different protein content and was commercially labeled as Reloxin***. More new toxins, such as botulinum toxin C, are poised to enter the market, making for an area of great new product introductions.

Botulinum toxin physiology

The botulinum toxin molecule is a 150 kilodalton protein consisting of a 100 kilodalton heavy chain and a 50 kilodalton side chain that are held together by a disulfide bond and a zinc atom. The mechanism by which botulinum toxin prevents the nerve to communicate with the muscle is somewhat complex. The heavy chain allows the botulinum toxin to attach to the nerve, and it enters into the nerve cell as a vesicle. It does this through a process known as endocytosis. As the vesicle enters the nerve, the heavy chain and light chain dissociate by breaking the disulfide bond, and the light chain is released into the nerve cell cytoplasm. The light chain then travels to the neuromuscular junction and cleaves the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. By cleaving this SNARE complex, the muscle remains uncontracted.

The disruption of the SNARE complex is not permanent and botulinum toxin does not damage the nerve. It takes four to seven days for the muscle paralysis to occur, and the effect lasts for two to six months, depending on the location of the paralyzed muscle, the dose of toxin administered and other patient variables. In time, the nerve ending begins to form new nerve sprouts, and the neuromuscular junction is restored, along with muscle function. At this point, the patient receives another injection. Repeated botulinum toxin injections may cause some muscle atrophy in time, and this contributes to the improvement in wrinkles seen one to two years after injection.

Injecting botulinum toxin

Botulinum toxin is purchased in freeze-dried sterile vials containing 100 units of lyophilized material. Originally, the toxin contained a fair amount of protein, which could cause an allergic reaction or the creation of antibodies to the toxin. Antibodies would mean that the botulinum toxin would no longer be effective in relaxing the muscle. Allergic reactions have been minimal to nonexistent and while the antibodies are a theoretical concern, they have not been widely seen in practice. Nevertheless, the newer botulinum toxins have a lower protein load.