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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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Normal NMDA receptor-mediated EPSCs in Ap oa1 mice. (A)No difference in input-output curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice. (B) No difference in I-V curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice.
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Figure 2: Normal NMDA receptor-mediated EPSCs in Ap oa1 mice. (A)No difference in input-output curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice. (B) No difference in I-V curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice.

Mentions: NMDA receptor in the ACC is critical for synaptic plasticity and chronic pain [9,35,37]. Therefore, we want to know whether the NMDA receptor-mediated EPSCs were normal in the transgenic mice. NMDA EPSCs were isolated in the presence of picrotoxin (100 μM) and non-NMDA receptor antagonist, CNQX (20 μM). Similarly, the input-output relationship and I-V curve were compared between two groups. We found that there was no significant difference in either input-output or I-V curve in ACC neurons from WT and transgenic mice (Figure 2A and 2B).


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)

Normal NMDA receptor-mediated EPSCs in Ap oa1 mice. (A)No difference in input-output curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice. (B) No difference in I-V curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Normal NMDA receptor-mediated EPSCs in Ap oa1 mice. (A)No difference in input-output curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice. (B) No difference in I-V curve of NMDA receptor-mediated EPSCs between WT and Ap oa1 mice.
Mentions: NMDA receptor in the ACC is critical for synaptic plasticity and chronic pain [9,35,37]. Therefore, we want to know whether the NMDA receptor-mediated EPSCs were normal in the transgenic mice. NMDA EPSCs were isolated in the presence of picrotoxin (100 μM) and non-NMDA receptor antagonist, CNQX (20 μM). Similarly, the input-output relationship and I-V curve were compared between two groups. We found that there was no significant difference in either input-output or I-V curve in ACC neurons from WT and transgenic mice (Figure 2A and 2B).

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