title: The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways.
abstract: BACKGROUND
  Our previous work demonstrated that persistent peripheral nociception (PPN) leads to synaptic plasticity and functional changes in the rat hippocampus. The protein kinase mTOR is a critical regulator of protein synthesis-dependent synaptic plasticity in the hippocampus as well as synaptic plasticity associated with central and peripheral pain sensitization. We examined the role of mTOR signaling in pain-associated entorhinal cortex (EC) - hippocampal synaptic plasticity to reveal possible cellular mechanisms underlying the effects of chronic pain on cognition and emotion.
  
  
  RESULTS
  Subcutaneous injection of bee venom (BV) into one hind paw to induce PPN resulted in sustained (> 8 h) mTOR phospho-activation and enhanced phosphorylation of the mTOR target p70 S6 kinase (S6K) in the hippocampus. The magnitude and duration of long-term potentiation (LTP) in both EC - dentate gyrus (DG) and EC - CA1 synaptic pathways were elevated in BV-treated rats as measured by microelectrode array recording. Moreover, the number of potentiated synapses in the hippocampus was markedly upregulated by BV-induced PPN. Both elevated mTOR-S6K signaling and enhanced LTP induced by BV injection were reversed by systemic injection of the mTOR inhibitor rapamycin (RAPA). Rats injected with BV exhibited markedly reduced ambulation and exploratory activity in the open field (signs of depression and anxiety) compared to controls, and these effects were also reversed by RAPA.
  
  
  CONCLUSIONS
  We suggest that PPN-induced enhancement of synaptic plasticity in EC - hippocampal pathways and the behavioral effects of PPN are dependent on mTOR-S6K signaling.
authors: Dan
authors: D
authors: Lyu
authors: Wenli
authors: W
authors: Yu
authors: Ning
authors: N
authors: Tang
authors: Ruirui
authors: R
authors: Wang
authors: Zhenyu
authors: Z
authors: Zhao
authors: Fang
authors: F
authors: Xie
authors: Yongjin
authors: Y
authors: He
authors: Department of Anesthesiology, Tianjin First Center Hospital, TianJin 300192, China. duhongyin@medmail.com.cn.
authors: Hongyin
authors: H
authors: Du
authors: Jun
authors: J
authors: Chen
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001514:Bee Venoms; D058570:TOR Serine-Threonine Kinases