Chen Jui Yen, Kubo Asako, Shinoda Masamichi, Okada-Ogawa Akiko, Imamura Yoshiki, Iwata Koichi
Department of Physiology, Nihon University School of Dentistry.
Department of Oral Diagnostic Sciences, Nihon University School of Dentistry.
J Oral Sci. 2020;62(1):13-17. doi: 10.2334/josnusd.18-0468.
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 TG neurons. The head-withdrawal reflex threshold for mechanical stimulation of the tongue was significantly lower in dry-tongue rats 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 TRPV1-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.
尽管口干症可导致持续性口腔疼痛，但其疼痛背后的机制尚未完全明确。为评估三叉神经节（TG）神经元中磷酸化p38（pp38）-TRPV4机制是否在舌干燥的机械性痛觉过敏中起作用，采用大鼠舌干燥模型研究伤害性反射以及TG神经元中pp38和TRPV4的表达。舌干燥大鼠对舌部机械刺激的撤头反射阈值显著低于假手术大鼠。舌干燥大鼠TG中TRPV4和pp38免疫反应性细胞的数量显著高于假手术大鼠。许多TRPV4免疫反应性细胞也呈pp38免疫反应性。诱导舌干燥后，TG中TRPV1免疫反应性细胞数量未发生变化。局部注射TRPV4阻断剂可减轻舌干燥大鼠的舌部机械性超敏反应。神经节内注射选择性p38丝裂原活化蛋白激酶抑制剂可消除舌干燥大鼠的舌部超敏反应，并抑制TG神经元中TRPV4的表达。目前的研究结果表明，TG神经元中通过p38磷酸化激活TRPV4参与了与舌干燥相关的机械性超敏反应。这些机制可能在与口干症相关的疼痛中起作用。
