Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia
1 Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, University of Toronto, Toronto, M5S 1A8, Canada
2 Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California 94130-0450, USA
3 Center for Systems Neurobiology, Departments of Pharmacology and Biomedical Engineering, Boston University, Boston, MA 02118, USA
4 Dept. of Biomedical Sciences, University of Maryland Dental School, Baltimore, MD 21201, USA
Molecular Pain 2006, 2:21 doi:10.1186/1744-8069-2-21Published: 15 June 2006
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.