背景:三叉神经痛(TN)是临床实践中常见且难以治疗的神经性疼痛障碍。先前的研究表明,Toll样受体4(TLR4)调节NF-κB通路的激活以影响大鼠的神经性疼痛。已知电压门控钠通道(VGSC)在神经性疼痛电活动中起重要作用。
目的:探讨眶下神经慢性压迫性损伤(ION-CCI)后TLR4是否通过TRAF6/NF-κBp65通路调节Nav1.3。
方法:对SD(SpragueDawley)大鼠进行ION-CCI建模。为了验证建模的成功,我们需要检测机械痛阈值和ATF3。然后,检测大鼠TG中TLR4、TRAF6、NF-κBp65、p-p65和Nav1.3的表达。随后,鞘内注射LPS-rs(TLR4拮抗剂),探讨TLR4/TRAF6/NF-κB通路在ION-CCI模型中的作用,C25-140(TRAF6抑制剂),和PDTC(NF-κBp65抑制剂)。
结果:ION-CCI手术可降低大鼠机械痛阈,增加ATF3、TLR4、TRAF6、NF-κBp-p65和Nav1.3的表达,但NF-κBp65表达无差异。注射TLR4/TRAF6/NF-κB通路拮抗剂或抑制剂后,Nav1.3表达降低,机械性痛阈升高。
结论:在ION-CCI大鼠模型中,大鼠三叉神经节TLR4通过TRAF6/NF-κBp65通路调节Nav1.3,TLR4拮抗剂可减轻ION-CCI大鼠的神经病理性疼痛。
BACKGROUND: Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4) modulates the activation of the NF-κB pathway to affect neuropathic pain in rats. Voltage-gated sodium channels (VGSCs) are known to play an important role in neuropathic pain electrical activity.
OBJECTIVE: To investigate whether TLR4 can regulate
Nav1.3 through the TRAF6/NF-κB p65 pathway after infraorbital nerve chronic constriction injury (ION-CCI).
METHODS: ION-CCI modeling was performed on SD (Sprague Dawley) rats. To verify the success of the modeling, we need to detect the mechanical pain threshold and ATF3. Then, detecting the expression of TLR4, TRAF6, NF-κB p65, p-p65, and
Nav1.3 in rat TG. Subsequently, investigate the role of TLR4/TRAF6/NF-κB pathway in ION-CCI model by intrathecal injections of LPS-rs (TLR4 antagonist), C25-140 (TRAF6 inhibitor), and PDTC (NF-κB p65 inhibitor).
RESULTS: ION-CCI surgery decreased the mechanical pain threshold of rats and increased the expression of ATF3, TLR4, TRAF6, NF-κB p-p65 and
Nav1.3, but there was no difference in NF-κB p65 expression. After inject antagonist or inhibitor of the TLR4/TRAF6/NF-κB pathway, the expression of
Nav1.3 was decreased and mechanical pain threshold was increased.
CONCLUSIONS: In the rat model of ION-CCI, TLR4 in the rat trigeminal ganglion regulates
Nav1.3 through the TRAF6/NF-κB p65 pathway, and TLR4 antagonist alleviates neuropathic pain in ION-CCI rats.