Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome
Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome
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DOI：
10.1097/j.pain.0000000000000322
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发表时间：
2015-12-01
期刊：
影响因子：
7.4
通讯作者：
Iwata, Koichi
中科院分区：
文献类型：
--
作者：
Shinoda, Masamichi;Takeda, Mamoru;Iwata, Koichi
灼口综合征的特征是感觉质量改变，即舌痛过敏。我们发现灼口综合征患者舌粘膜中青蒿素(Artemin，ARTN)的mRNA表达显著高于正常对照组，并用50%乙醇稀释的2，4，6-三硝基苯磺酸(TNBS)涂于舌背建立灼口综合征小鼠模型。TNBS治疗舌可引起持续性、长达一周的非炎症性舌痛，舌粘膜ARTN表达显著增加，舌热痛敏明显。在TNBS处理后，连续给予瞬时受体电位香草素1(TRPV1)拮抗剂SB366791或中和抗ARTN抗体完全抑制热痛敏。神经胶质细胞源性神经营养因子家族受体α3(GFRα3)阳性和TRPV1阳性的三叉神经节(TG)神经元的数量在TNBS治疗后显著增加，而在连续注射中和抗ARTN抗体后显著减少。经TNBS处理后，支配舌的三叉神经节细胞辣椒素诱发电流增强，舌局部注射中和抗ARTN抗体可抑制该电流。这些结果提示，在经TNBS处理的舌组织中，ARTN的过度表达增加了支配舌的TG神经元的膜兴奋性，从而增加了TRPV1的敏感性，从而导致热痛觉过敏。该模型可用于灼口综合征相关舌痛超敏反应的研究。
Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor alpha 3 (GFR alpha 3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome.