Neural Substrates of EA in Cardiovascular Control

EA 在心血管控制中的神经基质

• 批准号: 6747727
• 负责人: John C Longhurst
• 金额: $ 37.88万
• 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/6747727
• 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）：在过去的三十年里，针灸的使用在美国显着增加。虽然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，但对其影响的机制知之甚少。我们已经证明，电针（EA）在内关穴位正中神经减少交感神经兴奋心血管反射反应。通过阿片机制，涉及头端腹外侧延髓（rVLM）的μ和δ受体，EA抑制运动前交感神经元，这些神经元从正中神经和内脏（胆囊）神经接收会聚输入。然而，除了电针反应中的rVLM外，还可能存在涉及弓状核（ARC）和尾侧腹外侧导水管周围灰质（PAG）的长环反射。初步的解剖和电生理数据表明，这些区域在EA-心血管反应中发挥作用。目前的建议将使用一个综合的神经解剖学，电生理学和药理学的方法来评估ARC和PAG在这种反应中的作用，通过三个假设。首先，刺激内关穴增加ARC、PAG和rVLM中的c-Fos免疫反应性，而刺激胆囊仅增加PAG和rVLM中的c-Fos表达。这些区域中的细胞将与含有免疫反应性β-内啡肽或甲硫氨酸脑啡肽的神经元或轴突共同标记或紧密接近。第二，电针增加ARC神经元的活动，这些神经元投射到PAG，并通过阿片机制促进PAG中的内脏躯体会聚抑制。第三，PAG中接受来自正中神经和内脏神经的会聚抑制的神经元投射到rVLM，在rVLM中它们抑制交感前运动神经元的诱发活动和由此产生的心血管反应。了解电针内关穴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机制。这些知识，沿着目前的临床试验，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。