Botulinum toxin in the masseter muscle: Lingering effects of denervation

Abstract

Botulinum neurotoxins (BoNTs) are paralytic agents used to treat a variety of conditions in jaw muscles. Although their effect is considered temporary, there are reports of persistent functional changes. Using rabbits that received BoNT injection in one masseter muscle, the recovery of neuromuscular connection was investigated using nerve stimulation to evoke an electromyographic (EMG) response, and the recovery of muscle fibers was investigated using histological morphometry and bromodeoxyuridine (BrdU) immunohistochemistry. One month after treatment, evoked EMG was greatly reduced in both amplitude and duration, indicating that little reinnervation had taken place. Muscle fibers were atrophied and collagenous tissue was increased. Three months after treatment, evoked EMG duration was normal, indicating that at least some neuromuscular junctions were functional. Histologically, some muscle fibers were hypertrophied, some were still atrophied, and some appeared to have died. Fibrosis was still apparent amid slight increases in dividing cells and regenerating fibers. The histological effects of BoNT were evident although attenuated at a distance of about 1 cm from the injection level, but no regional differences could be discerned for the evoked EMGs. In conclusion, there were persistent muscular deficits seen 3 months after BoNT treatment that may have been caused by the failure of some affected muscle fibers to become reinnervated.

Bilateral treatment of the masseter with botulinum toxin: Consequences for mastication, muscle force and the mandibular condyle

“…11 Weight loss has been reported after bilateral masseter treatment in two other studies, one on adult rats 18 and one on juvenile macaques 19 although young rats receiving a lower dose did not lose mass. 20 In contrast to the contralateral hypertrophy observed after unilateral treatment, 7,17 the present bilateral study found no compensatory increase in size or activity by other muscles. Muscle coordination, responsible for the transverse excursion of the mandible during mastication, was also disrupted by bilateral treatment.…”

“…Rabbit masseters average 7 g, so 10 units/muscle is 1.4 units/g. Furthermore, a dosage of 10 units/masseter is the most common reported dose for rabbits, not only in our own work, but also that of others 15–17 . Surface EMG of mastication was repeated 48 h after injection and at Weeks 1, 2, 3, 5, 7, 9 and 11 post‐injection.…”

“…Furthermore, a dosage of 10 units/masseter is the most common reported dose for rabbits, not only in our own work, but also that of others. [15][16][17] Surface EMG of mastication was repeated 48 h after injection and at Weeks 1, 2, 3, 5, 7, 9 and 11 post-injection. Anaesthesia with wire EMG of mastication and incisor bite force was repeated at Weeks 1, 3, 7 and 11 and incisor bite force alone was recorded at Weeks 4 and 12.…”

Effect of Botulinum Toxin Injection on EMG Activity and Bite Force in Masticatory Muscle Disorder: A Randomized Clinical Trial

“…EMG and bite force are both important parameters in evaluating masticatory muscle performance and the measurement methods are reliable, convenient, and safe. In addition, decreased EMG implies that neuromuscular junctions have not been restored, which directly reflects BoNT-A's denervation effect [14]. Our study showed that the recovery of EMG occurs by 33 weeks and bite-force by 25 weeks after a moderate dose of BoNT-A.…”

“…The studies evaluating bony changes corroborate the drug's long-lasting hidden effect [12,13]. Permanent damage to neuromuscular function has also been considered [14]. The effect is likely to be cumulative if the structures are not allowed to recover before the repeated injections [15].…”