Chemodenervation From Physiology of the Skin, Third Edition

Female Face

“A series of articles appearing in Skin Inc. magazine on various topics related to skin physiology formed the initial basis for the original book Physiology of the Skin (Allured Business Media, 1998). Throughout the years, the topics expanded so much that this additional information required a new edition, thus Physiology of the Skin II (Allured Business Media, 2001) was issued. Now, new advances in basic science have made it necessary for a subsequent book, Physiology of the Skin, Third Edition, to be released by Allured Business Media in early 2011. Zoe Draelos, MD, has helped prepare this new edition. She is not only a highly skilled dermatologist, but also a first-rate scientist and the editor of a national medical journal. I am pleased that this third edition will continue to provide estheticians with the relevant information so necessary for the understanding and delivery of professional skin care. Although my interest will always be to help estheticians increase their knowledge of the skin, I am happy to pass the torch to the competent and professional Dr. Draelos.”

—Peter T. Pugliese, MD

Chemodenervation is a new area of anti-aging therapy in which selected nerves are disabled within the face and body to create a more pleasing, youthful appearance. It’s accomplished with a toxin produced by an anaerobic spore-forming bacteria known as Clostridium botulinum, which can accidentally be consumed in spoiled food and results in a condition known as botulism. Its symptoms begin with blurred vision, dry mouth, dizziness and nausea, and progress to total body paralysis.

The first study demonstrating a medical use for botulinum toxin was published in 1973 by Alan Scott, MD, a pediatric ophthalmologist, showing that the toxin could be used to weaken eye muscles in monkeys. It was not until 1977 that the first injections were tried in humans to treat visual problems, and in 1979, the U.S. Food and Drug Administration (FDA) gave approval for botulinum toxin to be used in the treatment of strabismus, the medical term for crossed eyes. The use of botulinum toxin for cosmetic purposes was FDA-approved in 2003 for the treatment of frown lines, known as glabellar rhytides.

Understanding botulinum toxin

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.

The vials arrive on dry ice and must be placed in a freezer for storage. They are removed immediately before use and diluted with sterile water. The dilution depends on the wishes of the user. Some physicians add 1 cc of water per vial while others prefer a more dilute botulinum toxin, adding 2 cc of sterile water. The effect produced by the botulinum toxin is dependent on the number of units injected and not the volume. Once the botulinum toxin is diluted, it is drawn up into tiny insulin syringes. In the package insert for botulinum toxin, it states that it must be used within four hours of reconstitution; however, it can be used without loss of potency for three weeks.

Facial uses of botulinum toxin

Botulinum toxin can be used to relax facial muscles, primarily above the nose on the upper face. Paralyzing muscles below the nose would affect the mouth, making smiling, speaking and eating difficult. Fillers, not botulinum toxin, are primarily used for anti-aging wrinkle therapy below the nose. In some instances, botulinum toxin can be used to relax the wrinkles above the upper lip or below the chin, but very small amounts are used in the hands of a skilled injector.

The most effective and most popular use of botulinum toxin is to relax frown-line wrinkles between the eyes. This is actually the original cosmetic use of botulinum toxin that was approved by the FD. The injection points correspond with the muscles that pull to allow the contraction of the skin between the eyes. There is significant variability between individuals in facial muscle movement and attachment, thus the injecting physician must customize the injections for each face. This is the art of using botulinum toxin. Failure to customize the treatment may result in unusual, unattractive results.

Botulinum toxin can also be used to relax other facial muscles. Areas for treatment include the crow’s-feet around the eyes, as well as forehead wrinkles. Care must be taken not to place the botulinum toxin too close to the eyes or vision may be affected. Additionally, some individuals use their forehead muscles to keep redundant eyelid skin out of their eyes. If the forehead muscles are over-relaxed, the eyebrows and eyelids will descend, creating an unattractive appearance and vision problems. Watching the patient carefully for muscle use is key before performing any injections, or problems may occur.

More advanced techniques for botulinum administration can result in other subtle facial improvements. For example, injections of very small amounts under the eye can relax the lower eyelid muscles and decrease crepey skin texture, but only if the patient has excellent skin elasticity. Under-eye injections can result in huge under-eye bags if the skin is lax. Injections can also be performed on either side of the nose to relax wrinkles known as “bunny lines,” which are considered unattractive when smiling. Again, small amounts must be used. The eyebrow can also be lifted in certain individuals by injecting at the lateral eyebrow, but this may not work in all females and is not aesthetically pleasing in males. These examples point out the art of patient selection, injection location and injection amount in obtaining the optimal anti-aging result.

Botulinum toxin off the face

Botulinum toxin can also be used for other purposes. The most common off-face treatment area is the armpit where unwanted sweating, known as hyperhidrosis, can be controlled by botulinum toxin injections. In people who experience excessive axillary sweating, botulinum toxin can interrupt the communication between the nerve and the sweat duct, thereby stopping sweating. Injections for this purpose must cover the entire hair-bearing area of both armpits and requires at least one whole bottle for treatment, which can be quite expensive. Injections can also be performed on the palms to decrease sweating. The injections in both areas must be very close to the skin’s surface to reach the sweat duct. Accidental deep injections in the hands can weaken the muscles and cause problems using the thumb and hand.

Injections for hyperhidrosis may last around six months, but there is great variability in response. These injections can also be quite painful, since the botulinum toxin must be placed every quarter inch until the entire area of sweating is covered. Sweating can be decreased with toxin injections, but not completely eliminated. It is important to help the patient develop realistic expectations.

Botulinum toxin can also be used to relax wrinkles on the neck and chest. For example, longitudinal muscle bands running down the neck can be relaxed, smoothing the neck skin. Very few units are used for the injections because too much toxin can make the neck muscles weak and cause problems speaking, swallowing and holding up the head. Botulinum toxin has also been placed in the upper chest to minimize wrinkling on the décolleté and provide a mild breast lift. These uses of toxin are very patient-specific, and the results are highly variable.

One last use for botulinum toxin off the face is in the treatment of migraine headaches. People who have a trigger point for their headaches that is located over a muscle may benefit. For example, patients with a trigger in the muscle between the eyes from frowning and squinting may find that botulinum toxin injections relax the muscle and prevent the onset of headaches. It is also possible to inject trigger points at the base of the scalp and on the neck.

The safety and versatility of botulinum toxin injections are sure to expand the applications for this technology. New and more inventive uses, including the possibility of topical cream botulinum toxin, are certainly on the horizon.

Side effects

Botulinum toxin is quite safe, if used in experienced hands. Proper dilution and correct injection techniques are a must. Problems arose several years ago because an inexperienced physician in Florida purchased animal botulinum toxin and injected an overdose into himself and several friends. One person required hospitalization due to difficulty breathing from the overdose. Only branded botulinum toxin designed for human use should ever be injected. Only people experienced with its use should be injectors, and the dose must be carefully calculated.

More common side effects of botulinum toxin injection are either too little or too much effect. Patients who elect to undergo toxin treatment need to realize that not every wrinkle on their face will go away with treatment. Toxin does not work where it is not injected. For example, a frown injection in the glabella will not help with crow’s-feet. Furthermore, an injection in the glabella is intended to relax the majority of the muscles and minimize—not eliminate—movement. If all movement is eliminated from the eyebrows, a “deer in the headlight” stunned look is achieved, which is quite unnatural and unattractive. Movement of the face is important to emote, and lack of movement is simply not human.

On occasion, too much botulinum toxin that has been poorly placed may cause problems, such as drooping of the eyebrows. The problem should be assessed by the injecting physician and changes should made to prevent a recurring problem. All physicians should keep an injection map detailing how many units were placed in a given location. This can prevent problems and ensure that the same excellent placement is used in the future. Fortunately, if a problem occurs, in time, the toxin effect will resolve and no harm will be done. There are no long-lasting side effects to botulinum toxin, and perhaps this accounts for its safety.

Esthetic considerations

Botulinum toxin is an important topic for the esthetician to consider. Understanding how botulinum toxin works and how it may influence other esthetic facial procedures is important. For example, a facial massage should not be performed immediately after botulinum toxin injections. It is possible to move the toxin to unwanted areas and relax muscles that should not be relaxed. It was also originally recommended that the patient remain upright for four hours after botulinum toxin injections and not fly in an airplane, again to prevent movement of the toxin. Although these restrictions may not be as important today, it is probably best to wait one day after botulinum toxin injections before offering any services. This will prevent any problems and minimize worries for the esthetician.

Zoe Draelos, MD, is a practicing board-certified dermatologist and a Fellow of the American Academy of Dermatologywith a research interest in cosmetics, toiletries and biologically active skin medications. She is in private practice in High Point, North Carolina, and is a consulting professor of dermatology at Duke University in Durham, North Carolina. In 1988, she founded Dermatology Consulting Services, serves on eight journal editorial boards and functions as the editor in chief of the Journal of Cosmetic Dermatology. She is also a member of the 2010–2011 Skin Inc. magazine advisory board.

Peter T. Pugliese MD, earned a Bachelor of Science degree from Franklin and Marshall College in Lancaster, Pennsylvania, and in 1957, a Doctor of Medicine from the School of Medicine at the University of Pennsylvania in Philadelphia. Since 1972, he has been engaged in the study of skin physiology, and is a member the American Academy of Dermatology, the Society of Investigative Dermatology, the Society of Bioengineers of the Skin, the American Chemical Society and the Society of Cosmetic Chemists. He has written more than 60 scientific papers, has published four books and is a member of the 2010–2011 Skin Inc. magazine advisory board.


* Botox is a trade name of Allergan, Inc., Irvine, CA.

** Myoblock is a trade name of Solstice Neurosciences, LLC, Louisville, KY.

*** Reloxin is a trade name of Medicis Pharmaceutical Corporation, Scottsdale, AZ.

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