Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex.
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.
Wu
Long-Jun
LJ
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
Steenland
Hendrik W
HW
Kim
Susan S
SS
Isiegas
Carolina
C
Abel
Ted
T
Kaang
Bong-Kiun
BK
Zhuo
Min
M
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009655:Octopamine / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D009655:Octopamine; D018698:Glutamic Acid; D000242:Cyclic AMP