Involvement of TRPV4 ionotropic channel in tongue mechanical hypersensitivity in dry-tongue rats
Involvement of TRPV4 ionotropic channel in tongue mechanical hypersensitivity in dry-tongue rats
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DOI：
10.2334/josnusd.18-0468
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发表时间：
2020-01-01
影响因子：
1.9
通讯作者：
Iwata, Koichi
中科院分区：
文献类型：
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作者：
Chen, Jui Yen;Kubo, Asako;Iwata, Koichi
虽然口干症会导致持续性的口腔疼痛，但这种疼痛背后的机制尚不清楚。为探讨三叉神经节(Tg)神经元中磷酸化的p38(Pp38)-TRPV4机制是否参与了舌燥症的机械性痛敏反应，采用大鼠舌燥症模型，研究了舌燥症大鼠三叉神经节神经元的伤害性反射及其pp38和TRPV4的表达。舌窝机械刺激舌头反射阈值明显低于假手术组。干舌大鼠三叉神经节内TRPV4和PP38免疫反应阳性细胞数明显高于假手术组。许多TRPV4-IR细胞也呈pp38免疫反应阳性。诱导舌燥后，舌质中TRPVI-IR细胞的数量无明显变化。局部注射TRPV4阻滞剂可减轻干舌大鼠的舌机能过敏反应。脊神经节内注射选择性p38 MAPK抑制剂可消除干舌大鼠的舌过敏反应，并抑制三叉神经节神经元TRPV4的表达。本研究结果提示，TG神经元通过p38磷酸化激活TRPV4参与了舌燥的机械性超敏反应。这些机制可能在与口干症相关的疼痛中起作用。
Although xerostomia can cause persistent oral pain, the mechanisms underlying such pain are not well understood. To evaluate whether a phosphorylated p38 (pp38)-TRPV4 mechanism in trigeminal ganglion (TG) neurons has a role in mechanical hyperalgesia of dry tongue, a rat model of dry tongue was used to study the nocifensive reflex and pp38 and TRPV4 expression in TO neurons. The head-withdrawal reflex threshold for mechanical stimulation of the tongue was significantly lower in dry-tongue nits than in sham rats. The numbers of TRPV4- and pp38-immunoreactive cells in the TG were significantly higher in dry-tongue rats than in sham rats. Many TRPV4-IR cells were also pp38-immunoreactive. The number of TRPVI-IR cells was unchanged in the TG after induction of tongue dryness. Local injection of a TRPV4 blocker attenuated tongue mechanical hypersensitivity in dry-tongue rats. Intraganglionic injection of a selective p38 MAP kinase inhibitor eliminated tongue hypersensitivity in dry-tongue rats and suppressed TRPV4 expression in TG neurons. The present findings suggest that TRPV4 activation via p38 phosphorylation in TG neurons is involved in mechanical hypersensitivity associated with dry tongue. These mechanisms may have a role in pain associated with xerostomia.