NOCICEPTION AND NMDA RECEPTOR PHOSPHORYLATION

描述(改编自《调查者摘要》)：慢性或持久性 在美国，疼痛是一个主要的健康问题，这导致了 医疗保健和生产力损失高达数十亿美元。两种症状 慢性或持续性疼痛，导致投诉数量最多 来自患者的是超感痛症(疼痛到通常非疼痛的刺激)和 痛觉过敏(对疼痛刺激的痛感增强)。 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂的研究进展 表明有相当大比例的痛觉异常和痛觉过敏 由脊髓NMDA受体介导。这项工作表明，有一个 脊髓NMDA受体活性在反应中的功能变化 对持续的伤害性刺激。NMDA受体受多种基因调控 因素，包括磷酸化。受体的磷酸化导致 感受器活性的增加。NMDA的两个亚单位 受体(NR1和NR2)对几种激酶有共同的位点，并具有活性 从脊髓中的一些激酶中提取出来的蛋白与 痛觉过敏和痛觉过敏。因此，这个项目的主要假设是 NMDA受体被持续的伤害性感觉所磷酸化。为了测试这一点 然而，假设，PI作为一个新的调查者，需要开发新的 他实验室里的技术。由于需要开发新技术， 这个应用程序的范围已经缩小到检验这样一个假设 NMDA受体的NR1亚单位在持续的过程中被磷酸化 伤害性感受。这一小额赠款申请将：1)允许PI开发和 检测免疫沉淀技术对NR1亚基的特异性 转染人HEK-293细胞，2)将这些技术应用于研究 体内NR1亚基的变化，以及3)评估NR1在体内的磷酸化变化 对伤害性刺激的反应。对……动态的全面理解 疼痛反应中NMDA受体的磷酸化是这个的最终目标 项目。这些知识应该会对脊髓疼痛有价值的见解。 治疗，并有望获得新的有效治疗方法。

DESCRIPTION (Adapted from the Investigator's Abstract): Chronic or persistent pain is a major health problem in the United States, which results in medical care and productivity losses in the billions of dollars. Two symptoms of chronic or persistent pain, which result in the greatest number of complaints from sufferers, are allodynia (pain to normally non-painful stimuli) and hyperalgesia (enhanced sensation of pain in response to painful stimuli). Recent work with antagonists for the N-methyl-D-aspartate (NMDA) receptor demonstrates that a significant proportion of allodynia and hyperalgesia is mediated by spinal cord NMDA receptors. This work suggests that there is a functional change in the activity of the spinal cord NMDA receptors in response to persistent nociceptive stimuli. NMDA receptors are regulated by a number of factors, including phosphorylation. Phosphorylation of the receptors results in an increase in the activity of the receptors. The two subunits of the NMDA receptor (NR1 and NR2) have consensus sites for several kinases, and activity from some of these kinases in the spinal cord has been associated with allodynia and hyperalgesia. Thus, the major hypothesis of this project is that NMDA receptors are phosphorylated by persistent nociception. To test this hypothesis, however, the PI, who is a new investigator, needs to develop new techniques in his laboratory. Because of the need to develop new techniques, the scope of this application has been narrowed to testing the hypothesis that the NR1 subunit of the NMDA receptor is phosphorylated during persistent nociception. This small grant application will: 1) allow the PI to develop and test the specificity of immunoprecipitation techniques on NR1 subunits transfected into HEK-293 cells, 2) transfer these techniques to the study of NR1 subunits in vivo, and 3) evaluate changes in NR1 phosphorylation in response to nociceptive stimuli. A complete understanding of the dynamics of NMDA receptor phosphorylation in response to pain is the ultimate goal of this project. This knowledge should lead to valuable insights into spinal cord pain processing and, hopefully, to new effective therapies.