Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia.
Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases, which then trigger biochemical cascades that lead to modifications in synaptic efficacy. Genetic and pharmacological techniques have been used to show a role for Ca2+/calmodulin-dependent kinase II (CaMKII) in synaptic plasticity and memory formation. However, it is not known if increasing CaMKII activity in forebrain areas affects behavioral responses to tissue injury. Using genetic and pharmacological techniques, we were able to temporally and spatially restrict the over expression of CaMKII in forebrain areas. Here we show that genetic overexpression of CaMKII in the mouse forebrain selectively inhibits tissue injury-induced behavioral sensitization, including allodynia and hyperalgesia, while behavioral responses to acute noxious stimuli remain intact. CaMKII overexpression also inhibited synaptic depression induced by a prolonged repetitive stimulation in the ACC, suggesting an important role for CaMKII in the regulation of cingulate neurons. Our results suggest that neuronal CaMKII activity in the forebrain plays a role in persistent pain.
Wei
Feng
F
Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, University of Toronto, Toronto, M5S 1A8, Canada. fwei001@umaryland.edu
Wang
Guo-Du
GD
Zhang
Chao
C
Shokat
Kevan M
KM
Wang
Huimin
H
Tsien
Joe Z
JZ
Liauw
Jason
J
Zhuo
Min
M
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D002908:Chronic Disease; D004558:Electric Stimulation; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006179:Gyrus Cinguli / Q000201:enzymology*; D006930:Hyperalgesia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D036881:Long-Term Synaptic Depression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010148:Intractable Pain / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D010766:Phosphorylation; D010812:Physical Stimulation; D016548:Prosencephalon / Q000201:enzymology*; D009435:Synaptic Transmission / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases