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Molecular Pain

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Open Access 01-12-2013 | Research

The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways

Authors: Dan Lyu, Wenli Yu, Ning Tang, Ruirui Wang, Zhenyu Zhao, Fang Xie, Yongjin He, Hongyin Du, Jun Chen

Published in: Molecular Pain | Issue 1/2013

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.

Conclusion

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.

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Title: The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways
Authors: Dan Lyu
Wenli Yu
Ning Tang
Ruirui Wang
Zhenyu Zhao
Fang Xie
Yongjin He
Hongyin Du
Jun Chen
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2013
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-9-64

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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