Messenger RNA profiling of rabbit quadriceps femoris after repeat injections of botulinum toxin: Evidence for a dynamic pattern without further structural alterations.

Introduction: Onabotulinum toxin type A (BoNT-A) is widely used clinically, but it may cause adverse effects. Earlier studies showed repeat BoNT-A injections did not cause progressive atrophy or function loss. The purpose of this study was to assess the influence of repeat BoNT-A injections into rabbit muscle on subsequent molecular alterations.

Methods: Twenty-two rabbits received 0, 1, 2, or 3 BoNT-A injections in the quadriceps femoris muscle at 3-month intervals and were euthanized 6 months after the last injection. Aliquots of both injected and contralateral muscle were frozen, and the total RNA quantified.

Results: Total RNA per illigram wet weight tissue was significantly elevated compared with control after 1, 2, or 3 BoNT-A injections. Analysis of mRNA levels for inflammatory molecules, proteinases, adipokines, and mesenchymal stem cells were elevated with increasing BoNT-A injections in injected leg and contralateral leg.

Discussion: Future studies should focus on the safety and possible complications of repeat BoNT-A treatments. Muscle Nerve 57: 487-493, 2018.