P2Y14 receptor in trigeminal ganglion contributes to neuropathic pain in mice
P2Y14 receptor in trigeminal ganglion contributes to neuropathic pain in mice
复制标题
三叉神经节中的 P2Y14 受体导致小鼠神经性疼痛
DOI：
10.1016/j.ejphar.2022.175211
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发表时间：
2022-08-17
影响因子：
5
通讯作者：
Shen, Jeifei
中科院分区：
文献类型：
--
作者：
Lin, Jiu;Fang, Xinyi;Shen, Jeifei
Trigeminal nerve injury is a common complication of various dental and oral procedures, which could induce trigeminal neuropathic pain but lack effective treatments. P2 purinergic receptors have emerged as novel therapeutic targets for such pain. Recent reports implied that the P2Y(14) receptor (P2Y(14)R) was activated and promoted orofacial inflammatory pain and migraine. However, the role and mechanism of P2Y(14)R in trigeminal neuropathic pain remain unknown. We induced an orofacial neuropathic pain model by chronic constriction injury of the infraorbital nerve (CCI-ION). Von-Frey tests showed that CCI-ION induced orofacial mechanical hypersensitivity. The increased activating transcription factor 3 (ATF3) expression in the trigeminal ganglion (TG) measured by immunofluorescence confirmed trigeminal nerve injury. Immunofluorescence showed that P2Y(14)R was expressed in trigeminal ganglion neurons (TGNs) and satellite glial cells (SGCs). RT-qPCR and Western blot identified increased expression of P2Y(14)R in TG after CCI-ION. CCI-ION also upregulated interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor-alpha (TNF-alpha) in TG. Notably, CCI-ION-induced mechanical hypersensitivity and pro-inflammatory cytokines production were decreased by a P2Y(14)R antagonist (PPTN). Trigeminal administration of P2Y(14)R agonist (UDP-glucose) evoked orofacial mechanical hypersensitivity and increased pro-inflammatory cytokines above in TG. Furthermore, CCI-ION induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 in TG, which also were reduced by PPTN. The inhibitors of ERK1/2 (U0126) and p38 (SB203580) decreased these upregulated pro-inflammatory cytokines after CCI-ION. Collectively, this study revealed that P2Y(14)R in TG contributed to trigeminal neuropathic pain via ERK- and p38-dependent neuroinflammation. Thus, P2Y(14)R may be a potential drug target against trigeminal neuropathic pain.
