Botox dispersion: Animal study documents functional weakness in non-injected muscles

Key Points

Calgary, Alberta - Botulinum toxin A injections produce a measurable loss of force in both targeted and nearby nontargeted muscles, according to a recent small study.

But representatives of Botox (botulinum toxin A) manufacturer Allergan say the study used a research-grade, laboratory preparation of the toxin that is not suitable for human use.

Researchers at the University of Calgary and at Wilfrid Laurier University in Waterloo, Ontario, injected one soleus muscle of six cats with 3.2 to 3.5 units of botulinum toxin A/kg, using the untreated leg as a control. They injected the toxin into each of two sites - one toward the proximal, the other toward the distal end of the soleus.

Researchers calculated decreases in peak force as the difference in the force produced by the injected limb and that produced by the contralateral limb as a percentage of the contralateral limb's peak force, at the length where peak contralateral force was obtained for each of three frequencies.

They then calculated the mean of these decreases across all frequencies for a given muscle.

Based on five usable comparisons for the soleus and four for the plantaris, researchers found a statistically significant decrease in force production in the botulinum toxin-injected soleus compared to the contralateral control across all muscle lengths and stimulation frequencies (p<0.001; Yaraskavitch M, Leonard T, Herzog W. J Biomech. 2008;41(4):897-902. Epub 2008 Jan 8).

Researchers also found a statistically significant decrease in force production of plantaris muscles in treated limbs versus nontreated limbs at all frequencies.

Four weeks after injection, soleus peak forces across all stimulation frequencies declined by an average of 29 percent, and peak forces in neighboring, noninjected plantaris muscles fell by around 14 percent.

"These results are of particular importance in therapeutic procedures where isolated muscles are targeted for treatment," the authors say.

"They should also be considered in neurophysiological studies in which botulinum toxin A injections are used to selectively diminish muscle function."

Allergan responds

However, Caroline Van Hove, vice president of corporate communications for Allergan, says the study involved "a laboratory experiment using doses that would not normally be used in a therapeutic situation."

Furthermore, Ms. Hove says it's inappropriate to draw conclusions about the safety of Botox in humans based on a study conducted in cats.

Dermatologists and cosmetic surgeons seem to agree that the study raises no undue concerns about cosmetic botulinum toxin treatments.

"If you inject 0.05 cc of Botox, it can spread for up to a centimeter. We've known that for more than 15 years. That's not news," says Edward B. Lack, M.D., past president of the American Academy of Cosmetic Surgery.

"As you increase the dilution and number of units, it's no surprise that you would get spread beyond the local injection area," says Joseph Sozio, M.D., principal at SkinCentre in New York.

With Botox Cosmetic, he says, "The experience of the physician to safely administer the appropriate dose in the appropriate location with appropriate instructions to the patient is important in decreasing the risks."

To that end, he suggests icing the area to decrease discomfort and spasming of the vessels, keeping patients' heads up during facial Botox injections, and asking them to move the target muscles so the toxin is absorbed locally.

Disclosures: The study authors and Dr. Sozio report no relevant financial interests.