title: Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex.
abstract: Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system. Investigations have mainly focused on the spinal mechanisms of neuropathic pain, and less is known about cortical changes in neuropathic pain. Here, we report that peripheral nerve injury triggered long-term changes in excitatory synaptic transmission in layer II/III neurons within the anterior cingulate cortex (ACC). Both the presynaptic release probability of glutamate and postsynaptic glutamate AMPA receptor-mediated responses were enhanced after injury using the mouse peripheral nerve injury model. Western blot showed upregulated phosphorylation of GluR1 in the ACC after nerve injury. Finally, we found that both presynaptic and postsynaptic changes after nerve injury were absent in genetic mice lacking calcium-stimulated adenylyl cyclase 1 (AC1). Our studies therefore provide direct integrative evidence for both long-term presynaptic and postsynaptic changes in cortical synapses after nerve injury, and that AC1 is critical for such long-term changes. AC1 thus may serve as a potential therapeutic target for treating neuropathic pain.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Wu
authors.forename: Hansen
authors.initials: H
authors.lastname: Wang
authors.forename: Xuehan
authors.initials: X
authors.lastname: Zhang
authors.forename: Kunjumon I
authors.initials: KI
authors.lastname: Vadakkan
authors.forename: Susan S
authors.initials: SS
authors.lastname: Kim
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Steenland
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D006179:Gyrus Cinguli / Q000502:physiology*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000235:genetics / Q000503:physiopathology*; D010543:Peroneal Nerve; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology