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Ceftriaxone Relieves Trigeminal Neuropathic Pain Through Suppression of Spatiotemporal Synaptic Plasticity via Restoration of Glutamate Transporter 1 in the Medullary Dorsal Horn.
Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2020-06-08 , DOI: 10.3389/fncel.2020.00199
Xiao Luo 1 , Ting He 2, 3 , Yan Wang 2, 3 , Jiang-Lin Wang 2, 4 , Xue-Bin Yan 1 , Hao-Cheng Zhou 1 , Rui-Rui Wang 2, 3 , Rui Du 2 , Xiao-Liang Wang 2, 3 , Jun Chen 2, 3 , Dong Huang 1
Affiliation  

Using a rat model of trigeminal neuropathic pain (TNP) produced by chronic compression of the infraorbital nerve (CCI-ION), we investigated the analgesic effect and the underlying mechanisms of ceftriaxone (Cef), a β-lactam antibiotic, that is thought to be a potent stimulator of glutamate transporter 1 (GLT-1). First, repeated intraperitoneal (i.p.) injections of Cef (200 mg/kg) for 5-days since Day 1 of CCI-ION could significantly relieve both mechanical and thermal pain hypersensitivity from day 10 after drug administration. Western blot and immunofluorescent results demonstrated that 5-days administration of Cef resulted in the restoration of GLT-1 expression to a level equivalent to the sham control which was dramatically lost under the TNP condition. Moreover, multi-electrode (8 × 8) array recordings of network field excitatory postsynaptic potentials (fEPSPs) were performed on the acutely dissociated medullary dorsal horn slice evoked by electrical stimulation of the trigeminal spinal tract. The results showed that the increased number of fEPSPs, induction rate, and maintenance of long-term potentiation caused by CCI-ION were significantly suppressed by 5-days administration of Cef. Taken together, the results indicate that Cef can relieve TNP through suppression of spatiotemporal synaptic plasticity via GLT-1 restoration in the medullary dorsal horn of the trigeminal nerve.



中文翻译:

头孢曲松钠通过恢复延髓背角的谷氨酸转运蛋白1,通过抑制时空突触可塑性来减轻三叉神经痛。

我们使用大鼠慢性眶下神经(CCI-ION)压迫产生的三叉神经性神经痛(TNP)的大鼠模型,研究了β-内酰胺类抗生素头孢曲松(Cef)的镇痛作用及其潜在机制,是谷氨酸转运蛋白1(GLT-1)的有效刺激剂。首先,自CCI-ION第1天起连续5天腹膜内(ip)注射Cef(200 mg / kg)可以从给药后第10天起显着缓解机械和热痛超敏反应。蛋白质印迹和免疫荧光结果表明,Cef的5天给药可使GLT-1表达恢复到与假对照相当的水平,在TNP条件下该表达明显丧失。此外,对三叉神经脊髓电刺激诱发的急速分离的延髓背角切片进行网络场兴奋性突触后电位(fEPSPs)多电极(8×8)阵列记录。结果表明,Cef-ion给药5天可明显抑制fEPSP的增加,诱导率和CCI-ION引起的长期增强。两者合计,结果表明头孢可以通过抑制时空突触可塑性来缓解TNP Cef 5天的给药显着抑制了由CCI-ION引起的长期增强和维持。两者合计,结果表明头孢可以通过抑制时空突触可塑性来缓解TNP Cef 5天的给药显着抑制了由CCI-ION引起的长期增强和维持。两者合计,结果表明头孢可以通过抑制时空突触可塑性来缓解TNP通过 GLT-1在三叉神经的延髓背角中恢复。

更新日期:2020-06-30
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