(347) A Myogenic Temporomandibular Disorder Enhances Migraine-Like Pain

Abstract

Migraine is commonly reported among individuals with temporomandibular disorders (TMDs), especially in the patients with myogenic TMDs. This relationship can potentially add to the significant burden already experienced by migraineurs. Despite the prevalence of this comorbidity, most of previous studies focus on its epidemiological statistics. To date, the pathophysiologic mechanisms related to the comorbidity of these two conditions remain elusive. To better address this issue, an animal model that represents the comorbidity of migraine-like pain and TMDs in a clinical population is needed. Thus, in the present study, we developed a new mouse model to study the comorbidity association between myogenic TMDs and migraine-like pain. We combined masseter muscle tendon ligation (MMTL) with systemic injection of nitroglycerin (NTG) in the new model, in which MMTL was carried out to produce a myogenic TMD and NTG was injected to induce migraine-like pain. We observed that a preexisting myogenic TMD not only prolongs NTG-induced migraine-like pain, but also enables a normally subthreshold dose of NTG to trigger migraine-like pain. Moreover, MMTL pretreatment significantly upregulated the expression of calcitonin gene-related peptide in the spinal trigeminal nucleus caudalis after NTG injection. We further observed that topiramate, an antiepileptic drug frequently used for migraine prophylaxis, significantly inhibits the myogenic TMD-enhanced migraine-like pain. Topiramate delayed the onset of TMD-enhanced migraine-like pain and reduced the pain thereafter in a dose-dependent manner. Together, our results indicate that a preexisting TMD can enhance migraine-like pain. The mouse model we developed in this study mimics the comorbid migraine headache and TMDs found in the clinical population. This model can be used to further investigate the underlying mechanisms of this comorbidity, and thus help us identify new therapeutic targets for such association.