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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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Related in: MedlinePlus

Enhancement of mEPSC frequency by octopamine in transgenic mice. (A) Sample traces showing the effect of octopamine (50 μM) on mEPSCs in Ap oa1 mice. (B) The cumulative probability plot for inter-event intervals showing that octopamine increased the frequency of mEPSCs in a neuron shown in A. The inset is the pooled data showing that frequency of mEPSCs was significantly increased. (C) No significant change in the amplitude of mEPSCs after octopamine application in transgenic mice.
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Figure 5: Enhancement of mEPSC frequency by octopamine in transgenic mice. (A) Sample traces showing the effect of octopamine (50 μM) on mEPSCs in Ap oa1 mice. (B) The cumulative probability plot for inter-event intervals showing that octopamine increased the frequency of mEPSCs in a neuron shown in A. The inset is the pooled data showing that frequency of mEPSCs was significantly increased. (C) No significant change in the amplitude of mEPSCs after octopamine application in transgenic mice.

Mentions: The results have indicated that octopamine targeted to presynaptic neurons to increase glutamate release in the ACC in transgenic mice. To further examine the pre- or postsynaptic effect of octopamine, we tested the effects of octopamine on mEPSCs in ACC pyramidal neurons in Ap oa1 mice. We found that bath-applied octopamine (50 μM) significantly increased the frequency of mEPSCs from 3.9 ± 0.9 Hz to 5.6 ± 1.1 Hz (n = 8, P < 0.01, paired t-test, Figure 5A and 5B). However, there is no significant change in the amplitude of mEPSCs before and after octopamine application (from 10.5 ± 1.5 pA to 9.6 ± 1.8 pA, n = 8, P = 0.29, Figure 5A and 5C). These results further supported the idea that activation of octopamine receptor by exogenous octopamine increased presynaptic glutamate release in the ACC in Ap oa1 mice.


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)

Enhancement of mEPSC frequency by octopamine in transgenic mice. (A) Sample traces showing the effect of octopamine (50 μM) on mEPSCs in Ap oa1 mice. (B) The cumulative probability plot for inter-event intervals showing that octopamine increased the frequency of mEPSCs in a neuron shown in A. The inset is the pooled data showing that frequency of mEPSCs was significantly increased. (C) No significant change in the amplitude of mEPSCs after octopamine application in transgenic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Enhancement of mEPSC frequency by octopamine in transgenic mice. (A) Sample traces showing the effect of octopamine (50 μM) on mEPSCs in Ap oa1 mice. (B) The cumulative probability plot for inter-event intervals showing that octopamine increased the frequency of mEPSCs in a neuron shown in A. The inset is the pooled data showing that frequency of mEPSCs was significantly increased. (C) No significant change in the amplitude of mEPSCs after octopamine application in transgenic mice.
Mentions: The results have indicated that octopamine targeted to presynaptic neurons to increase glutamate release in the ACC in transgenic mice. To further examine the pre- or postsynaptic effect of octopamine, we tested the effects of octopamine on mEPSCs in ACC pyramidal neurons in Ap oa1 mice. We found that bath-applied octopamine (50 μM) significantly increased the frequency of mEPSCs from 3.9 ± 0.9 Hz to 5.6 ± 1.1 Hz (n = 8, P < 0.01, paired t-test, Figure 5A and 5B). However, there is no significant change in the amplitude of mEPSCs before and after octopamine application (from 10.5 ± 1.5 pA to 9.6 ± 1.8 pA, n = 8, P = 0.29, Figure 5A and 5C). These results further supported the idea that activation of octopamine receptor by exogenous octopamine increased presynaptic glutamate release in the ACC in Ap oa1 mice.

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