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Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and
Feng Wei1, Guo-Du Wang, Chao Zhang
1Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, University of Toronto, Toronto, M5S 1A8, Canada. fwei001@umaryland.edu
Abstract:
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.
Insights
Overexpressing Ca2+/calmodulin-dependent kinase II (CaMKII) in the mouse forebrain reduced pain sensitization without affecting acute pain responses. This suggests CaMKII
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Synaptic plasticity is crucial for learning, memory, pain, and addiction.
- Glutamate NMDA receptor activation and protein kinases, like Ca2+/calmodulin-dependent kinase II (CaMKII), modulate synaptic efficacy.
- CaMKII's role in synaptic plasticity and memory is established, but its effect on forebrain pain responses is unclear.
Purpose of the Study:
- To investigate the role of Ca2+/calmodulin-dependent kinase II (CaMKII) in forebrain areas on behavioral responses to tissue injury.
- To determine if increased CaMKII activity influences pain sensitization and related behaviors.
Main Methods:
- Utilized genetic and pharmacological techniques for temporal and spatial restriction of CaMKII overexpression in mouse forebrain.
- Assessed behavioral responses to tissue injury, including allodynia and hyperalgesia.
- Examined synaptic depression in the anterior cingulate cortex (ACC) following prolonged stimulation.
Main Results:
- Genetic overexpression of CaMKII in the mouse forebrain selectively inhibited tissue injury-induced behavioral sensitization (allodynia and hyperalgesia).
- Behavioral responses to acute noxious stimuli remained unaffected by CaMKII overexpression.
- CaMKII overexpression inhibited synaptic depression in the ACC, indicating a role in regulating cingulate neurons.
Conclusions:
- Neuronal CaMKII activity in the forebrain plays a significant role in the development and maintenance of persistent pain.
- Targeting CaMKII in the forebrain may offer a therapeutic strategy for managing persistent pain conditions.
