The P2Y14 receptor in the trigeminal ganglion contributes to the maintenance of inflammatory pain
The P2Y14 receptor in the trigeminal ganglion contributes to the maintenance of inflammatory pain
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三叉神经节中的 P2Y14 受体有助于维持炎性疼痛
DOI：
10.1016/j.neuint.2019.104567
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发表时间：
2019-12-01
影响因子：
4.2
通讯作者：
Shen, Jie-fei
中科院分区：
文献类型：
--
作者：
Lin, Jiu;Zhang, Yan-yan;Shen, Jie-fei
三叉神经节(TG)神经元和卫星胶质细胞(SGCs)表达的P2Y嘌呤能受体参与炎症性疼痛和神经病理性疼痛。据报道，P2Y(14)受体在脊髓、背根神经节和三叉神经节表达。本研究探讨了P2Y(14)受体在SD大鼠口腔炎性疼痛的TG中的作用。外周注射完全弗氏佐剂(CFA)可引起机械性痛敏，TG中的P2Y(14)受体、胶质纤维酸性蛋白(GFAP)、白介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、C-C趋化因子CCL2、磷酸化细胞外信号调节蛋白1/2(p-ERK1/2)和磷酸化p38(p-p38)蛋白迅速上调。此外，免疫荧光染色证实了CFA诱导的P2Y(14)受体表达上调。免疫组织化学双重染色显示，P2Y(14)受体与谷氨酰胺合成酶(GS)和神经元核(NeuN)共存。最后，三叉神经注射选择性的P2Y(14)受体拮抗剂(PPTN)可减弱CFA诱导的机械性痛敏。PPTN还可降低GFAP、IL-1β、TNF-α、CCL2、p-ERK1/2和p-p38蛋白的表达。我们的结果表明，TG中的P2Y(14)受体可能通过调节SGCs的激活、释放细胞因子(IL-1β、TNF-α和CCL2)以及磷酸化ERK1/2和p38来参与口腔炎性疼痛。
P2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contribute to inflammatory and neuropathic pain. P2Y(14) receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y(14) receptor in the TG in inflammatory orofacial pain of Sprague-Dawley (SD) rats was investigated. Peripheral injection of complete Freund's adjuvant (CFA) induced mechanical hyperalgesia with the rapid upregulation of P2Y(14) receptor, glial fibrillary acidic protein (GFAP), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), C-C chemokine CCL2, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated p38 (p-p38) proteins in the TG. Furthermore, immunofluorescence staining confirmed the CFA-induced upregulation of P2Y(14) receptor. Double immunostaining showed that P2Y(14) receptor colocalized with glutamine synthetase (GS) and neuronal nuclei (NeuN). Finally, trigeminal injection of a selective antagonist (PPTN) of P2Y(14) receptor attenuated CFA-induced mechanical hyperalgesia. PPTN also decreased the upregulation of the GFAP, IL-1 beta, TNF-alpha, CCL2, p-ERK1/2, and p-p38 proteins. Our findings showed that P2Y(14) receptor in TG may contribute to orofacial inflammatory pain via regulating SGCs activation, releasing cytokines (IL-1 beta, TNF-alpha, and CCL2), and phosphorylating ERK1/2 and p38.