Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission
10.1007/s12264-020-00617-0
- Author:
Wen-Juan HAN
1
;
Hai-Ning WU
1
;
Hua HAN
1
;
Wen-Juan HAN
2
;
Sui-Bin MA
2
;
Rou-Gang XIE
2
;
Zhen-Zhen LI
2
;
Fei WANG
2
;
Sheng-Xi WU
2
;
Ceng LUO
2
;
Wen-Bin WU
3
;
Fu-Dong WANG
3
;
Xiu-Li CAO
4
;
Min-Hua ZHENG
4
;
Dong-Hao WANG
5
Author Information
1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fourth Military Medical University
2. Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University
3. The Fourth Regiment, School of Basic Medicine, Fourth Military Medical University
4. Department of Medical Genetics and Developmental Biology, Fourth Military Medical University
5. National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, College of Life Sciences, Shaanxi Normal University
- Publication Type:Journal Article
- Keywords:
Inflammatory pain;
Long-term potentiation;
Peripheral sensitization;
Ttyh1
- From:
Neuroscience Bulletin
2021;37(4):478-496
- CountryChina
- Language:Chinese
-
Abstract:
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 inflammation-evoked 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.
