Mechanisms of CNS Autonomic Regulation by EA

EA对中枢神经系统自主调节的机制

• 批准号: 6989078
• 负责人: John C Longhurst
• 金额: $ 28.66万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-20 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989078
• 关键词: AMPA receptors; NMDA receptors; acupuncture /acupressure; afferent nerve; autonomic nervous system; autonomic reflex; blood pressure; cardiovascular system; cats; electrophysiology; electrostimulus; gallbladder; glutamate receptor; glutamates; high performance liquid chromatography; laboratory rat; medulla oblongata; microdialysis; neurophysiology; neuroregulation; opioid receptor; radioimmunoassay; vascular smooth muscle nervous control; vasomotion

DESCRIPTION (provided by applicant): Acupuncture increasingly is becoming a mainstay of treatment for a number of diseases. Although its acceptance by physicians and scientists in the western world is increasing, reluctance remains strong because its mechanisms of action are poorly defined. This application represents a competitive renewal of our grant to study the neural influence of electroacupuncture (EA) on the autonomic nervous and cardiovascular systems. In the previously funded period we have shown that EA at Neiguan and Zusanli acupoints reduces demand-induced myocardial ischemia by reducing the pressor response during excitatory cardiovascular reflexes. This influence occurs, in part, in the rostral ventral lateral medulla (rVLM) where acupuncture causes prolonged inhibition of premotor sympathoexcitatory neurons that receive convergent input from visceral and somatic nerves. This modulation involves the opioid system, particularly mu- and delta-opioid receptors, suggesting that endorphins and enkephalins are important neurotransmitters. The present grant will extend our prior studies by proposing five mechanistic hypotheses relevant to EA. We will determine: 1) the role of glutamate and its ionotropic NMDA and AMPA excitatory amino acid receptors in rVLM excitatory convergent input during reflex and EA stimulation using pharmacological antagonism; 2) the synaptic location of opioid inhibition of rVLM excitation using both microdialysis and exogenous glutamate to examine pre- and post-synaptic influences; 3) the function of nociceptin and its associated ORL-1 receptor in EA-related modulation of rVLM neuronal activity; 4) using pharmacological and electrophysiological approaches, the transmitter mechanisms of prolonged inhibition of rVLM activity by EA, focusing on opioids, nociceptin and y-aminobutyric acid; and 5) spinal cord dorsal horn delta- and K-opioid and nociceptin ORL-1 mechanisms in segmental and extra-segmental influence of EA on sensory input. These studies will provide important new information about the mechanisms underlying the influence of EA on the autonomic and cardiovascular systems. Much of this knowledge will be applicable clinically. Improved understanding of acupuncture will assist practicing acupuncturists and will provide physicians and scientists with a stronger rationale for using and studying this alternative therapy.

描述（由申请人提供）：针灸越来越多地成为多种疾病的治疗中的主要治疗方法。尽管西方世界中医生和科学家的接受程度在增加，但由于其作用机制的定义很差，因此不情愿仍然很强大。该应用代表了我们赠款的竞争性更新，以研究电针仪（EA）对自主神经神经和心血管系统的神经影响。在先前资助的时期，我们已经表明，Neiguan和Zusanli穴位的EA通过在兴奋性心血管反射期间减少压力反应来减少需求引起的心肌缺血。这种影响部分发生在the鼻腹侧髓质（RVLM）中，其中针灸会导致长时间抑制前交感神经能激发性神经元，这些神经元从内脏和体细胞神经接收到收敛的输入。该调节涉及阿片类药物系统，尤其是Mu-和Delta-阿片受体，表明内啡肽和enkephalins是重要的神经递质。目前的赠款将通过提出与EA相关的五种机械假设来扩展我们先前的研究。我们将确定：1）使用药理拮抗作用，在反射和EA刺激过程中，谷氨酸及其离子型NMDA和AMPA兴奋性氨基酸受体在RVLM兴奋性收敛输入中的作用； 2）使用微透析和外源性谷氨酸抑制阿片类药物抑制RVLM激发的突触位置，以检查前后突触后的影响； 3）Nocteptin及其相关的ORL-1受体在RVLM神经元活性的调节中的功能； 4）使用药理学和电生理方法，通过EA延长RVLM活性的发射机机制，重点是阿片类药物，Nocceptin和Y-氨基丁酸； 5）EA对EA对感觉输入的节段和分段影响中的脊髓背角三角形和K-阿普素和NociTptin ORL-1机制。这些研究将提供有关EA对自主神经和心血管系统影响的机制的重要新信息。这些知识的大部分将在临床上适用。提高对针灸的理解将有助于实践针灸师，并将为医生和科学家提供使用和研究这种替代疗法的更强理由。