Role of medullary astroglial glutamine synthesis in tooth pulp hypersensitivity associated with frequent masseter muscle contraction.

Abstract

Background The mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle hyperalgesia remain largely underinvestigated. In the present study, we aimed to determine whether masseter muscle contraction induced by daily electrical stimulation influences the mechanical head-withdrawal threshold and genioglossus electromyography activity caused by the application of capsaicin to the upper first molar tooth pulp. We further investigated whether astroglial glutamine synthesis is involved in first molar tooth pulp hypersensitivity associated with masseter muscle contraction. Methods The first molar tooth pulp was treated with capsaicin or vehicle in masseter muscle contraction or sham rats, following which the astroglial glutamine synthetase inhibitor methionine sulfoximine or Phosphate buffered saline (PBS) was applied. Astroglial activation was assessed via immunohistochemistry. Results The mechanical head-withdrawal threshold of the ipsilateral masseter muscle was significantly decreased in masseter muscle contraction rats than in sham rats. Genioglossus electromyography activity was significantly higher in masseter muscle contraction rats than sham rats. Glial fibrillary acidic protein-immunoreactive cell density was significantly higher in masseter muscle contraction rats than in sham rats. Administration of methionine sulfoximine induced no significant changes in the density of glial fibrillary acidic protein-immunoreactive cells relative to PBS treatment. However, mechanical head-withdrawal threshold was significantly higher in masseter muscle contraction rats than PBS-treated rats after methionine sulfoximine administration. Genioglossus electromyography activity following first molar tooth pulp capsaicin treatment was significantly lower in methionine sulfoximine-treated rats than in PBS-treated rats. In the ipsilateral region, the total number of phosphorylated extracellular signal-regulated protein kinase immunoreactive cells in the medullary dorsal horn was significantly smaller upon first molar tooth pulp capsaicin application in methionine sulfoximine-treated rats than in PBS-treated rats. Conclusions Our results suggest that masseter muscle contraction induces astroglial activation, and that this activation spreads from caudal to the obex in the medullary dorsal horn, resulting in enhanced neuronal excitability associated with astroglial glutamine synthesis in medullary dorsal horn neurons receiving inputs from the tooth pulp. These findings provide significant insight into the mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle contraction.

• Authors: Tetsuro Watase, Kohei Shimizu, Kinuyo Ohara, Hiroki Komiya, Kohei Kanno, Keisuke Hatori, Noboru Noma, Kuniya Honda, Yoshiyuki Tsuboi, Ayano Katagiri, Masamichi Shinoda, Bunnai Ogiso, Koichi Iwata
• Journal: Molecular pain (Mol Pain) 2018 Jan-Dec Vol. 14 Pg. 1744806918763270 ISSN: 1744-8069 [Electronic] United States
• PMID: 29448913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• Glutamine
• Methionine Sulfoximine
• Extracellular Signal-Regulated MAP Kinases
• Capsaicin

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Capsaicin (pharmacology)
• Dental Pulp (drug effects, metabolism, pathology, physiopathology)
• Electric Stimulation
• Electromyography
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Glutamine (metabolism)
• Hyperalgesia (pathology, physiopathology)
• Male
• Masseter Muscle (drug effects, pathology, physiopathology)
• Medulla Oblongata (drug effects, metabolism, physiopathology)
• Methionine Sulfoximine (administration & dosage, pharmacology)
• Molar (pathology)
• Muscle Contraction (drug effects)
• Phosphorylation (drug effects)
• Posterior Horn Cells (drug effects, metabolism)
• Rats, Sprague-Dawley