One Molecule, Different Circuits? What Botulinum Toxin Can and Cannot Reveal About Craniocervical Comorbidity

Botulinum neurotoxin type A (BoNT-A) is used across coexisting craniocervical conditions, and therapeutic response is often overinterpreted as evidence of a shared generator. The bruxism literature shows why. Across six controlled studies with event-level outcome measurement, reported effects on event frequency track not dose or injection field but whether the rule used to detect an event could follow the amplitude the toxin had just reduced; none yet combines a placebo arm with an amplitude-independent event definition. This targeted critical narrative review interprets representative evidence mechanistically rather than assessing efficacy. It examines chronic migraine, tension-type headache, myogenous temporomandibular disorders, and bruxism, with somatosensory tinnitus as a cross-modal boundary case. Efficacy is protocol-specific in chronic migraine and uncertain elsewhere. Tracing studies locate somatosensory routes to the cochlear nucleus in the spinal trigeminal and dorsal column nuclei; a direct mesencephalic-trigeminal-to-cochlear projection has not been demonstrated in the tracing literature reviewed, so somatic–auditory plausibility does not establish the masticatory proprioceptive route invoked by muscle-targeted rationales. Because BoNT-A affects motor output, peripheral nociceptive signaling, and muscle spindle input—the last of these probably differing in availability across injection fields—we frame it as a site-dependent, multi-output perturbation. That pharmacology is established; what is offered here is the inferential framing and the anatomical constraint following from it.