Fang Li, Wu Jing, Lin Qing, Willis William D
Department of Anatomy and Neurosciences, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
J Neurosci. 2002 May 15;22(10):4196-204. doi: 10.1523/JNEUROSCI.22-10-04196.2002.
Calcium/calmodulin-dependent protein kinase II (CaMK II) is found throughout the CNS. It regulates calcium signaling in synaptic transmission by phosphorylating various proteins, including neuronal membrane receptors and intracellular transcription factors. Inflammation or injuries to peripheral tissues cause long-lasting increases in the responses of central nociceptive neurons to innocuous and noxious stimuli. This change can occur independently of alterations in the responsiveness of primary afferent neurons and has been termed central sensitization. Central sensitization is a form of activity-dependent plasticity and results from interactions in a set of intracellular signaling pathways, which modulate nociceptive transmission. Here we demonstrate an increased expression and phosphorylation of CaMK II in rat spinal dorsal horn neurons after noxious stimulation by intradermal injection of capsaicin. Local administration of a CaMK II inhibitor in the spinal cord significantly inhibits the enhancement of responses of spinal nociceptive neurons and changes in exploratory behavior evoked by capsaicin injection. In addition, spinal CaMK II activity enhances phosphorylation of AMPA receptor GluR1 subunits during central sensitization produced by capsaicin injection. This study reveals that CaMK II contributes to central sensitization in a manner similar to its role in the processes underlying long-term potentiation.
钙/钙调蛋白依赖性蛋白激酶II（CaMK II）存在于整个中枢神经系统中。它通过磷酸化各种蛋白质（包括神经元膜受体和细胞内转录因子）来调节突触传递中的钙信号。外周组织的炎症或损伤会导致中枢伤害性神经元对无害和有害刺激的反应长期增加。这种变化可以独立于初级传入神经元反应性的改变而发生，被称为中枢敏化。中枢敏化是一种活动依赖性可塑性形式，由一组调节伤害性传递的细胞内信号通路相互作用产生。在这里，我们证明在皮内注射辣椒素进行伤害性刺激后，大鼠脊髓背角神经元中CaMK II的表达和磷酸化增加。在脊髓中局部施用CaMK II抑制剂可显著抑制脊髓伤害性神经元反应的增强以及辣椒素注射引起的探索行为变化。此外，在辣椒素注射产生的中枢敏化过程中，脊髓CaMK II活性增强了AMPA受体GluR1亚基的磷酸化。这项研究表明，CaMK II以与其在长期增强作用基础过程中所起作用类似的方式促成中枢敏化。
