Abstract
Migraine is commonly reported among patients with temporomandibular disorders (TMDs), especially myogenic TMD. The pathophysiologic mechanisms related to the comorbidity of the two conditions remain elusive. In the present study, we combined masseter muscle tendon ligation (MMTL)-produced myogenic TMD with systemic injection of nitroglycerin (NTG)-induced migraine-like hypersensitivity in mice. Facial mechanical allodynia, functional allodynia, and light-aversive behavior were evaluated. Sumatriptan, an FDA-approved medication for migraine, was used to validate migraine-like hypersensitivity. Additionally, we examined the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis using immunohistochemistry. We observed that mice with MMTL pretreatment have a prolonged NTG-induced migraine-like hypersensitivity, and MMTL also enabled a non-sensitizing dose of NTG to trigger migraine-like hypersensitivity. Systemic injection of sumatriptan inhibited the MMTL-enhanced migraine-like hypersensitivity. MMTL pretreatment significantly upregulated the protein level of CGRP in the spinal trigeminal nucleus caudalis after NTG injection. Our results indicate that a pre-existing myogenic TMD can upregulate NTG-induced trigeminal CGRP and enhance migraine-like hypersensitivity.
Highlights
Both temporomandibular disorder (TMD) and migraine are highly prevalent and debilitating conditions [1,2]
By combining the masseter muscle tendon ligation (MMTL)-produced myogenic TMD with NTG-induced migraine-like hypersensitivity, we investigated the effect of a pre-existing myogenic TMD on migraine-like pain and the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis (Sp5C)
Establishing an animal model that mimics the occurrence of enhanced migraine-like hypersensitivity in TMD patients is the central premise for investigating such comorbid condition
Summary
Both temporomandibular disorder (TMD) and migraine are highly prevalent and debilitating conditions [1,2]. TMD is a set of complex conditions of the masticatory muscles, the temporomandibular joint (TMJ), and associated structures. The prevalence of TMD has been reported as 5% in the United. Among all the signs and symptoms produced by TMD, pain is the most significant as it directly reduces quality of life and the daily activities of affected individuals [5]. The etiology of TMD pain is multifactorial, including arthrogenic- and myogenic-originated disorders. The mechanisms underlying migraine headache have been studied for many years, yet it remains unclear how transition from acute to chronic migraine headache occurs and whether other facial pain conditions (e.g., TMD) affect chronicity of migraine headache
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