Anatomical Rationale for Motor Endplate Zone-Targeted Botulinum Toxin Injection in the Masseter Muscle: A Hypothesis-Generating Review

Botulinum neurotoxin (BoNT) injection into the masseter muscle is used in selected conditions associated with excessive or painful masseter activity, including oromandibular dystonia, masseter-related myalgia, and bruxism-associated masticatory muscle pain. However, clinical outcomes and adverse-event profiles vary widely, partly because injection technique, dose, dilution, injection depth, anatomical targeting, patient selection, and injector experience have not been consistently standardized. This review examines the anatomical and pharmacological rationale for motor endplate zone (MEZ)-targeted BoNT injection into the masseter muscle. MEZ-targeted injection is not presented as an established clinical guideline or as a proven superior technique but as a hypothesis-generating framework for future controlled studies. Anatomical and electrophysiological studies indicate that neuromuscular junctions in the masseter muscle are concentrated within relatively restricted MEZs. From a pharmacological perspective, delivery of BoNT close to these zones may allow more efficient neuromuscular blockade with lower doses, although direct clinical evidence demonstrating superiority over conventional techniques remains insufficient. Reported adverse events may be influenced by excessive dosing, inaccurate injection depth, diffusion into adjacent structures, or repeated high-dose injections. Future studies should evaluate anatomically informed, dose-minimized injection strategies using clearly defined clinical populations, standardized diagnostic criteria, detailed reporting of injection technique, objective functional outcomes, and systematic adverse-event assessment.