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Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex
Journal article   Open access   Peer reviewed

Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex

Long-Jun Wu, Hendrik W Steenland, Susan S Kim, Carolina Isiegas, Ted Abel, Bong-Kiun Kaang and Min Zhuo
Molecular pain, Vol.4(1), pp.40-40
09/29/2008
DOI: 10.1186/1744-8069-4-40
PMCID: PMC2570662
PMID: 18823548
url
https://doi.org/10.1186/1744-8069-4-40View
Published (Version of record) Open Access

Abstract

Both presynaptic and postsynaptic alterations are associated with plastic changes of brain circuits, such as learning and memory, drug addiction and chronic pain. However, the dissection of the relative contributions of pre- and postsynaptic components to brain functions is difficult. We have previously shown peripheral inflammation caused both presynaptic and postsynaptic changes and calcium-stimulated cyclic AMP (cAMP) pathway in the anterior cingulate cortex (ACC) is critical in the synaptic plasticity and behavioral sensitization to pain. It remains to be elucidated whether presynaptic or postsynaptic modulation by cAMP in the ACC could be sufficient for enhancing inflammatory pain. In order to address this question, we took advantage of a novel transgenic mouse model, heterologously expressing an Aplysia octopamine receptor (Ap oa 1 ). This receptor is G protein-coupled and selectively activates the cAMP pathway. We found that activation of Ap oa 1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro . Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain. The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.
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