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Articles, Development/Plasticity/Repair

Mitochondrial Ca2+ Uptake Is Essential for Synaptic Plasticity in Pain

Hee Young Kim, Kwan Yeop Lee, Ying Lu, Jigong Wang, Lian Cui, Sang Jeong Kim, Jin Mo Chung and Kyungsoon Chung
Journal of Neuroscience 7 September 2011, 31 (36) 12982-12991; DOI: https://doi.org/10.1523/JNEUROSCI.3093-11.2011
Hee Young Kim
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Kwan Yeop Lee
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Ying Lu
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Jigong Wang
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Lian Cui
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Sang Jeong Kim
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Jin Mo Chung
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Kyungsoon Chung
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Abstract

The increase of cytosolic free Ca2+ ([Ca2+]c) due to NMDA receptor activation is a key step for spinal cord synaptic plasticity by altering cellular signal transduction pathways. We focus on this plasticity as a cause of persistent pain. To provide a mechanism for these classic findings, we report that [Ca2+]c does not trigger synaptic plasticity directly but must first enter into mitochondria. Interfering with mitochondrial Ca2+ uptake during a [Ca2+]c increase blocks induction of behavioral hyperalgesia and accompanying downstream cell signaling, with reduction of spinal long-term potentiation (LTP). Furthermore, reducing the accompanying mitochondrial superoxide levels lessens hyperalgesia and LTP induction. These results indicate that [Ca2+]c requires downstream mitochondrial Ca2+ uptake with consequent production of reactive oxygen species (ROS) for synaptic plasticity underlying chronic pain. These results suggest modifying mitochondrial Ca2+ uptake and thus ROS as a type of chronic pain therapy that should also have broader biologic significance.

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The Journal of Neuroscience: 31 (36)
Journal of Neuroscience
Vol. 31, Issue 36
7 Sep 2011
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Mitochondrial Ca2+ Uptake Is Essential for Synaptic Plasticity in Pain
Hee Young Kim, Kwan Yeop Lee, Ying Lu, Jigong Wang, Lian Cui, Sang Jeong Kim, Jin Mo Chung, Kyungsoon Chung
Journal of Neuroscience 7 September 2011, 31 (36) 12982-12991; DOI: 10.1523/JNEUROSCI.3093-11.2011

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Mitochondrial Ca2+ Uptake Is Essential for Synaptic Plasticity in Pain
Hee Young Kim, Kwan Yeop Lee, Ying Lu, Jigong Wang, Lian Cui, Sang Jeong Kim, Jin Mo Chung, Kyungsoon Chung
Journal of Neuroscience 7 September 2011, 31 (36) 12982-12991; DOI: 10.1523/JNEUROSCI.3093-11.2011
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