A pre-existing myogenic temporomandibular disorder increases trigeminal calcitonin gene-related peptide and enhances nitroglycerin-induced hypersensitivity in mice

Hui Shu, Sufang Liu, Yuanyuan Tang, Brian L. Schmidt, John C. Dolan, Larry L. Bellinger, Phillip R. Kramer, Steven D. Bender, Feng Tao

Research output: Contribution to journalArticlepeer-review

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 lightaversive 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.

Original languageEnglish (US)
Article number4049
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
StatePublished - Jun 1 2020

Keywords

  • Calcitonin gene-related peptide
  • Comorbidity
  • Migraine pain
  • Spinal trigeminal nucleus caudalis
  • Temporomandibular disorder

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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