PDF(Pubmed)
Abstract：
The CXCR2 chemokine receptor is known to have a significant impact on the initiation and control of inflammatory processes. However, its specific involvement in the sensation of itch is not yet fully understood. In this study, we aimed to elucidate the function of CXCR2 in the trigeminal ganglion (TG) by utilizing orofacial itch models induced by incision, chloroquine (CQ), and histamine. Our results revealed a significant up-regulation of CXCR2 mRNA and protein expressions in the primary sensory neurons of TG in response to itch stimuli. The CXCR2 inhibitor SB225002 resulted in notable decrease in CXCR2 protein expression and reduction in scratch behaviors. Distal infraorbital nerve (DION) microinjection of a specific shRNA virus inhibited CXCR2 expression in TG neurons and reversed itch behaviors. Additionally, the administration of the PI3K inhibitor LY294002 resulted in a decrease in the expressions of p-Akt, Akt, and CXCR2 in TG neurons, thereby mitigating pruritic behaviors. Collectively, we report that CXCR2 in the primary sensory neurons of trigeminal ganglion contributes to orofacial itch through the PI3K/Akt signaling pathway. These observations highlight the potential of molecules involved in the regulation of CXCR2 as viable therapeutic targets for the treatment of itch.
摘要：
已知CXCR2趋化因子受体对炎症过程的启动和控制具有显著影响。然而,它在瘙痒感觉中的具体参与尚未完全理解。在这项研究中,我们旨在阐明CXCR2在三叉神经节（TG）中的功能，利用切口诱导的口面瘙痒模型，氯喹（CQ），和组胺.我们的结果表明，响应瘙痒刺激，TG的初级感觉神经元中CXCR2mRNA和蛋白质表达显着上调。CXCR2抑制剂SB225002导致CXCR2蛋白表达的显著降低和划痕行为的降低。特定shRNA病毒的眶下神经（DION）远端注射抑制了TG神经元中CXCR2的表达并逆转了瘙痒行为。此外,PI3K抑制剂LY294002的给药导致p-Akt的表达减少，Akt,和CXCR2在TG神经元，从而减轻瘙痒行为。总的来说，我们报道三叉神经节初级感觉神经元中的CXCR2通过PI3K/Akt信号通路促进口面瘙痒。这些观察结果突出了参与CXCR2调节的分子作为治疗瘙痒的可行治疗靶标的潜力。
