and reduces

Forebrain overexpression of CaMKII abolishes cingulate long term depression mechanical allodynia and thermal hyperalgesia. 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 Ca 2+ /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.

前脑钙/钙调蛋白依赖性激酶II（CaMKII）的过度表达消除扣带回长时程抑制、机械性异常性疼痛和热痛觉过敏 摘要 活动依赖性突触可塑性在学习与记忆、持续性疼痛和药物成瘾中具有重要作用。谷氨酸N - 甲基 - D - 天冬氨酸（NMDA）受体激活可刺激多种蛋白激酶，进而触发生化级联反应，导致突触效能改变。遗传学和药理学技术已被用于证明Ca²⁺/钙调蛋白依赖性激酶II（CaMKII）在突触可塑性和记忆形成中的作用。然而，尚不清楚前脑区域CaMKII活性的增加是否会影响对组织损伤的行为反应。利用遗传学和药理学技术，我们能够在时间和空间上限制前脑区域CaMKII的过度表达。在此我们表明，小鼠前脑CaMKII的基因过度表达选择性地抑制组织损伤诱导的行为敏化，包括异常性疼痛和痛觉过敏，而对急性有害刺激的行为反应保持不变。CaMKII过度表达还抑制了前扣带回皮质（ACC）中长时间重复刺激诱导的突触抑制，这表明CaMKII在扣带回神经元的调节中具有重要作用。我们的研究结果表明，前脑中神经元CaMKII的活性在持续性疼痛中起作用。