Some Relaxing News: Exploring How The Neuromodulator Landscape Is Evolving From Botox to Revance

Neuromodulators, also termed neurotoxins that are used in plastic surgery are derived from botulinum toxin A, a substance produced by Clostridium botulinum bacteria. Botox is the original product, with Dysport, Xeomin and Jeuveau also on the market in the United States.  I like the term relaxers for these medicines as it points out the muscle relaxing mechanism by which they work.

History of Cosmetic Use

Botulinum toxin A medicine and the illness botulism are totally different.  Many medicines are metabolic blockers –they block a specific pathway.  If they are very specific and precise that can be helpful for therapeutic purposes.  The relaxer medicines are very specific with a very high therapeutic index (the difference between the effective dose and the toxic dose).  The botulinum toxin was isolated in the 1940’s.  Very controlled amounts were used to treat some specific medical conditions leading to an FDA approval for Botox in 1989 for blepharospasm and strabismus, conditions relating to muscles around the eye.  In 2002 (Botox just had it’s 20th anniversary in April 2022) the medicine was approved for cosmetic treatments of wrinkles between the eyebrows.  Subsequent approvals of Botox for hyperhydrosis (2010), migraines (2013) and other medical applications have occurred.  New botulinum toxin A products have also been approved Dysport (2009), Xeomin (20110, and Jeuveau as the 4th.

These medications act at the nerve endings where vesicles of acetylcholine are released and dumped into the space between the nerve endings and muscle fibers causing the muscle to contract.  Botulinum toxin A  binds irreversibly to the SNAP25 receptor on the acetyl choline vesicles preventing them from releasing.  This leaves the muscle unable to contract until new vesicles are generated which takes several months.  Depending on dosing, the muscle relaxes partially or totally.

Treatment Experience

Treatments include carefully assessing the dynamic component of any feature which is caused by muscle contraction and the resting tension in the muscle.  Fixed wrinkling resulting from aging changes in the skin is not well treated by relaxers.  Careful assessment must also be made of where the muscle is active which requires good anatomic knowledge and an observant provider.  This tells us where the medicine needs to be placed.  The treatment targets the muscle not the wrinkle itself.    Numbing gel, topically applied cooling or vibrating devices are used to blunt the sensation of injecting.  The medicine is dotted in with small injections in several areas over the targeted muscle.  This only takes a few minutes after which you can return to work or routine social activities.  Every provider has different rules, but I ask my patients to avoid bending lifting and sports for the next four hours.  Over a few days the effect begins to show, peaking after a couple of weeks and lasting a few months.  This varies from person to person depending on their muscle dynamics and the dosing and injection scheme used.

Cosmetic Uses for Relaxers

The most common uses for relaxers, often performed simultaneously, include:

  • 11’s –the vertical lines formed between the eyebrows
  • Forehead lines –the horizontal lines across the forehead at rest or with animation
  • Crow’s feet –wrinkling at the corner of the eye, if dynamic, made worse on smiling

Other commonly treated areas:

  • Bunny lines –little wrinkling by the side of the nose
  • Chin –for cobblestone like dimpling during animation
  • Lip stick bleed lines –if there is a dynamic component
  • Marionette lines –if there is a dynamic component
  • Platysmal bands –vertical bands in the neck if visible and no significant loose skin

Newer uses:

  • Lip flip –helps to roll up the upper lip, providing more vermillion show (pink lip)
  • Masseter –to soften a square jaw to a more oval facial shape
  • Nefertiti lift –jawline injection to float up and sharpen mild laxity

Acetyl choline blocking also affects sweat production and sebum production.  Microinjections to modulate oiliness of skin, pore size and potentially acne are being tried.  Injections for hypertrophic scars also sometimes include small doses of relaxers.


Role of Neuromodulators/Takeaways:

  • Not for laxity prevention or treatment
  • Not for volume loss
  • Excellent for dynamic rhytids, the dynamic component of some folds
  • The future may include really different relaxer products with longer durability or topical application. Impossible to say when or if they will be approved.
  • Neuromodulators (relaxers) are the #1 cosmetic treatment with 65 million injections in 2020 according to statistics from The Aesthetic Society.  By comparison, fillers are the #2 treatment with 1.3million injections and liposuction, the most common surgical cosmetic treatment was performed 296,000 times in the same year.

Why are neuromodulators the most popular treatment?  Reason include the easy experience, speed, lack of downtime but most important the effect is exceptionally pleasing to most people, leaving them looking rested and natural in a way that really resonates and makes them love their appearance.