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

LongJun Wu, Hendrik W. Steenland, Susan S. Kim, Carolina Isiegas, Ted Abel, Bong Kiun Kaang, Min Zhuo

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 oa1). This receptor is G protein-coupled and selectively activates the cAMP pathway. We found that activation of Ap oa1 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.

Original languageEnglish (US)
Article number40
JournalMolecular Pain
Volume4
DOIs
StatePublished - Sep 29 2008
Externally publishedYes

Fingerprint

Gyrus Cinguli
Cyclic AMP
Glutamic Acid
Pain
Octopamine
Inflammation
Aplysia
Neuronal Plasticity
Brain
Acute Pain
Microinjections
G-Protein-Coupled Receptors
Synaptic Transmission
Chronic Pain
Transgenic Mice
Substance-Related Disorders
Dissection
Learning
Calcium

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex. / Wu, LongJun; Steenland, Hendrik W.; Kim, Susan S.; Isiegas, Carolina; Abel, Ted; Kaang, Bong Kiun; Zhuo, Min.

In: Molecular Pain, Vol. 4, 40, 29.09.2008.

Research output: Contribution to journalArticle

Wu, LongJun ; Steenland, Hendrik W. ; Kim, Susan S. ; Isiegas, Carolina ; Abel, Ted ; Kaang, Bong Kiun ; Zhuo, Min. / Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex. In: Molecular Pain. 2008 ; Vol. 4.
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