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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)12982-12991
Number of pages10
JournalJournal of Neuroscience
Issue number36
StatePublished - Sep 7 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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