Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission

• 作者: Wen-Juan Han Sui-Bin Ma Wen-Bin Wu Fu-Dong Wang Xiu-Li Cao Dong-Hao Wang Hai-Ning Wu Rou-Gang Xie Zhen-Zhen Li Fei Wang Sheng-Xi Wu Min-Hua Zheng Ceng Luo Hua Han
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original Articles
• 页码范围: 478-496
• 页数: 19页
• 语种: 英文

摘要

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases.However,its functional significance in pain processing is not understood.By disrupting the gene encoding Ttyh1,we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice,along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state.More importantly,the peripheral inflammationevoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice.Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release.Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief.Thus,in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.