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Title: PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity
Author: Duan, Bo ; Liu, Di-Shi ; Huang, Yu ; Zeng, Wei-Zheng ; Wang, Xiang ; Yu, Hui ; Zhu, Michael X. ; Chen, Zhe-Yu ; Xu, Tian-Le(徐天乐)
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2012
Volume: 32, Issue:18, Pages:6351-6363
Keyword: DORSAL-HORN NEURONS ; INFLAMMATION-INDUCED HYPERALGESIA ; PROTEIN-KINASE-C ; RAT SPINAL-CORD ; GROWTH-FACTOR-I ; NEUROTROPHIC FACTOR ; NMDA RECEPTOR ; CENTRAL SENSITIZATION ; NEUROPATHIC PAIN ; SENSORY NEURONS
Subject: Neurosciences & Neurology
Corresponding Author: Xu, TL (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Biochem & Mol Cell Biol,Neurosci Div, 280 S Chongqing Rd, Shanghai 200025, Peoples R China,xu-happiness@shsmu.edu.cn
English Abstract: Central neural plasticity plays a key role in pain hypersensitivity. This process is modulated by brain-derived neurotrophic factor (BDNF) and also involves the type 1a acid-sensing ion channel (ASIC1a). However, the interactions between the BDNF receptor, tropomyosin-related kinase B (TrkB), and ASIC1a are unclear. Here, we show that deletion of ASIC1 gene suppressed the sustained mechanical hyperalgesia induced by intrathecal BDNF application in mice. In both rat spinal dorsal horn neurons and heterologous cell cultures, the BDNF/TrkB pathway enhanced ASIC1a currents via phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB/Akt) cascade and phosphorylation of cytoplasmic residue Ser-25 of ASIC1a, resulting in enhanced forward trafficking and increased surface expression. Moreover, in both rats and mice, this enhanced ASIC1a activity was required for BDNF-mediated hypersensitivity of spinal dorsal horn nociceptive neurons and central mechanical hyperalgesia, a process that was abolished by intrathecal application of a peptide representing the N-terminal region of ASIC1a encompassing Ser-25. Thus, our results reveal a novel mechanism underlying central sensitization and pain hypersensitivity, and reinforce the critical role of ASIC1a channels in these processes.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1487
Appears in Collections:神经所(总)_期刊论文

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Duan, Bo; Liu, Di-Shi; Huang, Yu; Zeng, Wei-Zheng; Wang, Xiang; Yu, Hui; Zhu, Michael X.; Chen, Zhe-Yu; Xu, Tian-Le.PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity,JOURNAL OF NEUROSCIENCE,2012,32(18):6351-6363
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