Neural Substrates of EA in Cardiovascular Control

EA 在心血管控制中的神经基质

• 批准号: 7078637
• 负责人: John C Longhurst
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7078637
• 关键词: acupuncture /acupressure; antidromic impulse; blood pressure; cardiovascular disorder therapy; cardiovascular function; cats; electrodes; electrostimulus; enkephalins; gallbladder; gene expression; hypothalamus; neural inhibition; neuroimmunomodulation; neuroregulation; nontherapeutic iontophoresis; opioid receptor; periaqueductal gray matter; protooncogene; splanchnic nerves; stereotaxic techniques

DESCRIPTION (provided by applicant): The use of acupuncture has increased markedly in the US over the last three decades. Although NCCAM is sponsoring clinical trials on acupuncture in cardiovascular disease, including hypertension, coronary artery disease or arrhythmias, the mechanisms underlying its influence are poorly understood. We have shown that electro acupuncture (EA) at the Neiguan acupoint over the median nerve reduces sympathoexcitatorycardiovascular reflex responses. Through an opioid mechanism, involving mu and delta receptors in the rostral ventrolateral medulla (rVLM), EA inhibits premotor sympathoexcitatory neurons that receive convergent input from the median and splanchnic (gallbladder) nerves. However, a long loop reflex likely exists involving the arcuate nucleus (ARC) and the caudal ventrolateral periaqueductal gray (PAG), in addition to the rVLM in the EA response. Preliminary anatomical and electrophysiological data suggest that these regions play a role in EA-cardiovascular response. The present proposal will use a combined neuroanatomical, electrophysiological and pharmacological approach to evaluate the role of the ARC and PAG in this response through three hypotheses. First, stimulation of the Neiguan acupoint increases c-Fos immunoreactivity in the ARC, PAG and rVLM whereas stimulation of the gallbladder increases c-Fos expression only in the PAG and rVLM. Cells in these regions will either be co-labeled or in close proximity to neurons or axons containing immunoreactive beta-endorphin or met-enkephalin. Second, EA increases activity in neurons of the ARC, which project to the PAG and through an opioid mechanism facilitates visceral somatic convergent inhibition in the PAG. Third, neurons in the PAG receiving convergent inhibition from the median and splanchnic nerves project to the rVLM where they inhibit evoked activity in sympathetic premotor neurons and the resulting cardiovascular responses. Understanding the pathways and the central neural integration by which EA at the Neiguan acupoint inhibits reflex excitatory cardiovascular responses will provide a greater understanding of the mechanisms underlying the beneficial modulation of the cardiovascular system by this alternative therapy. Such knowledge, along with the current clinical trials, will encourage acceptance of this therapy by scientists and clinicians in the US and other Western countries.

描述（由申请人提供）：过去三十年来，针灸的使用在美国显着增加。尽管 NCCAM 正在赞助针灸治疗心血管疾病（包括高血压、冠状动脉疾病或心律失常）的临床试验，但其影响背后的机制却知之甚少。我们已经证明，电针（EA）正中神经上的内关穴可减少交感兴奋性心血管反射反应。通过涉及延髓头端腹外侧 (rVLM) 中的 mu 和 delta 受体的阿片类药物机制，EA 可抑制从正中神经和内脏（胆囊）神经接收汇聚输入的运动前交感兴奋神经元。然而，除了 EA 反应中的 rVLM 之外，还可能存在涉及弓状核 (ARC) 和尾部腹外侧导水管周围灰质 (PAG) 的长环反射。初步解剖学和电生理学数据表明这些区域在 EA 心血管反应中发挥作用。目前的提案将结合神经解剖学、电生理学和药理学方法，通过三个假设来评估 ARC 和 PAG 在这种反应中的作用。首先，刺激内关穴会增加 ARC、PAG 和 rVLM 中的 c-Fos 免疫反应性，而刺激胆囊只会增加 PAG 和 rVLM 中的 c-Fos 表达。这些区域中的细胞将被共同标记或靠近含有免疫反应性β-内啡肽或甲硫脑啡肽的神经元或轴突。其次，EA 增加 ARC 神经元的活性，该神经元投射到 PAG，并通过阿片类机制促进 PAG 中的内脏体细胞收敛抑制。第三，PAG 中的神经元受到来自正中神经和内脏神经的会聚抑制，投射到 rVLM，在那里它们抑制交感前运动神经元的诱发活动以及由此产生的心血管反应。了解内关穴位电针抑制反射性兴奋性心血管反应的途径和中枢神经整合，将有助于更好地理解这种替代疗法对心血管系统有益调节的潜在机制。这些知识以及当前的临床试验将鼓励美国和其他西方国家的科学家和临床医生接受这种疗法。