1 Department of Anatomy, Nihon University School of Dentistry, Japan.
2 Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Japan.
Mol Pain. 2018 Jan-Dec;14:1744806918763270. doi: 10.1177/1744806918763270. Epub 2018 Feb 15.
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.
与咬肌痛觉过敏相关的牙髓 hypersensitivity 的机制在很大程度上仍未得到充分研究。在本研究中，我们旨在确定每日电刺激引起的咬肌收缩是否会影响辣椒素应用于上颌第一磨牙牙髓时引起的机械性头部撤回阈值和颏舌肌肌电图活动。我们进一步研究了星形胶质细胞谷氨酰胺合成是否参与了与咬肌收缩相关的第一磨牙牙髓 hypersensitivity。
在咬肌收缩或假手术大鼠的第一磨牙牙髓上用辣椒素或载体处理后，应用星形胶质细胞谷氨酰胺合成酶抑制剂蛋氨酸亚砜或磷酸盐缓冲盐水 (PBS)。通过免疫组织化学评估星形胶质细胞激活。
与假手术大鼠相比，咬肌收缩大鼠的同侧咬肌机械性头部撤回阈值明显降低。咬肌收缩大鼠的颏舌肌肌电图活动明显高于假手术大鼠。咬肌收缩大鼠的胶质纤维酸性蛋白免疫反应性细胞密度明显高于假手术大鼠。与 PBS 处理相比，蛋氨酸亚砜胺给药不会引起胶质纤维酸性蛋白免疫反应性细胞密度的显著变化。然而，在蛋氨酸亚砜胺给药后，咬肌收缩大鼠的机械性头部撤回阈值明显高于 PBS 处理大鼠。与 PBS 处理大鼠相比，在第一磨牙牙髓用辣椒素处理后，蛋氨酸亚砜胺处理大鼠的颏舌肌肌电图活动明显较低。在同侧区域，在第一磨牙牙髓用辣椒素处理后，蛋氨酸亚砜胺处理大鼠的背根髓灰质中磷酸化细胞外信号调节蛋白激酶免疫反应性细胞总数明显小于 PBS 处理大鼠。
我们的结果表明，咬肌收缩诱导星形胶质细胞激活，并且这种激活从延髓的 obex 向尾侧扩散，导致与牙髓传入神经元的星形胶质细胞谷氨酰胺合成相关的神经元兴奋性增强。这些发现为与咬肌收缩相关的牙髓 hypersensitivity 的机制提供了重要的见解。
