ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.
ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.
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DOI：
10.1177/1744806916641680
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Iwata K
中科院分区：
文献类型：
--
作者：
Nakaya Y;Tsuboi Y;Okada-Ogawa A;Shinoda M;Kubo A;Chen JY;Noma N;Batbold D;Imamura Y;Sessle BJ;Iwata K
众所周知，口干会引起口腔内结构的剧烈疼痛，许多口干患者一直遭受口内疼痛的折磨。在制定适当的治疗方案时，研究与口干相关的口内疼痛的机制是至关重要的，但详细的机制尚不完全清楚。为了评估与口干相关的疼痛机制，我们建立了干舌大鼠模型。因此，我们检测了干舌大鼠三叉神经尾侧亚核的机械反射或热伤害反射、磷酸化的细胞外信号调节激酶和磷酸化的GluR1-IR免疫组织化学以及单个神经元的活性。舌头干燥后第7天，机械刺激而非热刺激的头退缩反射阈值显著降低。第7天，干舌大鼠三叉神经尾侧亚核痛觉神经元的机械反应（而非热反应）明显增强。与假药大鼠相比，在第7天对干舌大鼠的舌头进行有害刺激后，三叉神经脊髓尾侧亚核中磷酸化的细胞外信号调节激酶免疫反应细胞的数量也显著增加。在内源性给予丝裂原激活的蛋白激酶激酶1抑制剂PD98059时，机械头退缩反射阈值（HWT）的下降被逆转。与给药大鼠相比，腹腔内给药PD98059后，三叉神经尾侧亚核神经元活性和磷酸化的细胞外信号调节激酶免疫反应细胞数量也显著减少。在干舌大鼠三叉神经脊髓尾侧亚核中发现磷酸化GluR1-IR细胞数量增加，而pd98059组的磷酸化GluR1-IR细胞数量明显低于对照组。这些发现表明，pERK-pGluR1级联参与了三叉神经脊髓尾侧亚核痛觉神经元的中枢致敏，从而导致与舌头干燥相关的舌头机械痛觉过敏。
Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying.