Spinal Excitatory Amino Acids in Postoperative Pain

术后疼痛中的脊髓兴奋性氨基酸

• 批准号: 6830201
• 负责人: TIMOTHY JOHN BRENNAN
• 金额: $ 29.4万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6830201
• 关键词: AMPA receptors; NMDA receptors; aspartate; behavior test; disease /disorder model; dorsal horn; electrophysiology; excitatory aminoacid; glutamate receptor; glutamates; hyperalgesia; inhibitor /antagonist; laboratory rat; microdialysis; neural information processing; neurochemistry; neurons; neurophysiology; neuropsychology; pathologic process; postoperative state; protein structure function; stimulus /response

DESCRIPTION (provided by applicant): Postoperative, incisional pain is a unique but common form of acute pain. Since effective postoperative analgesia reduces morbidity following surgery, new treatments continue to be investigated. The proposal is dedicated toward studies of the mechanisms that subserve acute postoperative pain, It is through the study of mechanisms that a better understanding of incisional pain can be achieved and new treatments can be advanced. The work proposed will specifically characterize the mechanisms for incisional pain at the neuronal level in the dorsal horn. Neurochemical and neurophysiological approaches will be used in concert to examine the mechanisms that contribute to the development and maintenance of primary and secondary hyperalgesia after incision. Our working hypothesis is that glutamate and aspartate act on nonNMDA (N-methyl-D-aspartate) receptors to induce changes in spinal cord processing and to maintain the sensitization of dorsal horn neurons. Specifically, we will: (1) Investigate the effect of NMDA, nonNMDA and metabotropic excitatory amino acid receptor antagonists on the response properties of spinal cord dorsal horn neurons sensitized by an incision. (2) Determine the role of NMDA and nonNMDA receptors, including calcium-permeable AMPA (amino-3-hydroxy-5-methylisoxazole-4-propionic acid ) receptors and kainate receptors, on the secondary hyperalgesia caused by an incision of the gastrocnemius region. Neurophysiologic studies will determine the effect of NMDA and nonNMDA receptor antagonists on a specific measure of central sensitization of dorsal horn neurons caused by incision and in so doing reveal the specific contribution of central sensitization to pain behaviors. (3) Confirm that incision results in an increased basal or evoked release of the excitatory amino acids, aspartate and glutamate, in the spinal cord dorsal horn. These studies will use microdialysis to examine the time course and magnitude of glutamate and aspartate release during and after incision under quiescent conditions and conditions of repetitive stimulation. Insights gained into the role of excitatory amino acids, and in particular the role of calcium-permeable AMPA and kainate receptors, will advance our understanding of postoperative incisional pain and provide a basis for rationale design of new pharmacologic treatment

描述（由申请人提供）：术后，切口疼痛是一种独特的疼痛 但常见的急性疼痛。由于有效的术后镇痛可减少 手术后的发病率，新的治疗方法仍在研究中。这 提案致力于研究促进急性发作的机制 术后疼痛，是通过机制的研究，更好的 可以了解切口疼痛并可以开发新的治疗方法 先进的。拟议的工作将具体描述以下机制的特征： 背角神经元水平的切口痛。神经化学和 将同时使用神经生理学方法来检查其机制 有助于小学和中学的发展和维持 切口后痛觉过敏。我们的工作假设是谷氨酸和 天冬氨酸作用于非 NMDA（N-甲基-D-天冬氨酸）受体，诱导 脊髓处理并维持背角的敏化 神经元。具体来说，我们将：（1）研究NMDA、nonNMDA和 代谢型兴奋性氨基酸受体拮抗剂对反应的影响 切口致敏的脊髓背角神经元的特性。 (2) 确定 NMDA 和非 NMDA 受体（包括钙渗透性受体）的作用 AMPA（氨基-3-羟基-5-甲基异恶唑-4-丙酸）受体和 红藻氨酸受体，对切口引起的继发性痛觉过敏 腓肠肌区域。神经生理学研究将确定其效果 NMDA 和非 NMDA 受体拮抗剂对中枢神经系统的特定测量 切口引起的背角神经元的敏化揭示了 中枢敏化对疼痛行为的具体贡献。 (3) 确认切口导致基础或诱发释放增加 脊髓背侧的兴奋性氨基酸、天冬氨酸和谷氨酸 喇叭。这些研究将使用微透析来检查时间进程和 切口期间和之后谷氨酸和天冬氨酸释放量 静态条件和重复刺激条件。获得的见解 兴奋性氨基酸的作用，特别是 钙渗透性 AMPA 和红藻氨酸受体，将增进我们对 术后切口疼痛，为新方案的合理设计提供依据 药物治疗