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

Wu LJ, Steenland HW, Kim SS, Isiegas C, Abel T, Kaang BK, Zhuo M - Mol Pain (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. longjun.wu@utoronto.ca

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.

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Presynaptic action of octopamine in transgenic mice. (A) Representative traces (upper) and pooled results (lower) showing that octopamine significantly decreased pair-pulse facilitation in transgenic mice. (B) Octopamine (50 μM) had no effect on puff-applied glutamate-induced current in transgenic mice.
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Figure 4: Presynaptic action of octopamine in transgenic mice. (A) Representative traces (upper) and pooled results (lower) showing that octopamine significantly decreased pair-pulse facilitation in transgenic mice. (B) Octopamine (50 μM) had no effect on puff-applied glutamate-induced current in transgenic mice.

Mentions: The enhanced amplitude of EPSCs by octopamine in Ap oa1 mice may be due to increased function of postsynaptic AMPA receptor or presynaptic glutamate release. To address the issue, we tested pair-pulse ratio, a commonly used criteria to study the presynaptic release [10], in ACC pyramidal neurons by octopamine in transgenic mice. Paired stimuli with 50 ms intervals were applied and pair-pulse facilitation (PPF) was calculated before and after application of octopamine in transgenic mice (Figure 4A). We found that bath application of octopamine (50 μM) significantly decreased PPF from 1.48 ± 0.09 to 1.28 ± 0.06 (n = 14, P < 0.05, paired t-test, Figure 4A). Therefore, the results demonstrate the enhanced presynaptic glutamate release after activation of Ap oa1 by application of octopamine.


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

Wu LJ, Steenland HW, Kim SS, Isiegas C, Abel T, Kaang BK, Zhuo M - Mol Pain (2008)

Presynaptic action of octopamine in transgenic mice. (A) Representative traces (upper) and pooled results (lower) showing that octopamine significantly decreased pair-pulse facilitation in transgenic mice. (B) Octopamine (50 μM) had no effect on puff-applied glutamate-induced current in transgenic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570662&req=5

Figure 4: Presynaptic action of octopamine in transgenic mice. (A) Representative traces (upper) and pooled results (lower) showing that octopamine significantly decreased pair-pulse facilitation in transgenic mice. (B) Octopamine (50 μM) had no effect on puff-applied glutamate-induced current in transgenic mice.
Mentions: The enhanced amplitude of EPSCs by octopamine in Ap oa1 mice may be due to increased function of postsynaptic AMPA receptor or presynaptic glutamate release. To address the issue, we tested pair-pulse ratio, a commonly used criteria to study the presynaptic release [10], in ACC pyramidal neurons by octopamine in transgenic mice. Paired stimuli with 50 ms intervals were applied and pair-pulse facilitation (PPF) was calculated before and after application of octopamine in transgenic mice (Figure 4A). We found that bath application of octopamine (50 μM) significantly decreased PPF from 1.48 ± 0.09 to 1.28 ± 0.06 (n = 14, P < 0.05, paired t-test, Figure 4A). Therefore, the results demonstrate the enhanced presynaptic glutamate release after activation of Ap oa1 by application of octopamine.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. longjun.wu@utoronto.ca

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.

Show MeSH
Related in: MedlinePlus