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）：在过去的三十年中，美国使用针灸明显增加。尽管NCCAM正在赞助有关心血管疾病中针灸的临床试验，包括高血压，冠状动脉疾病或心律不齐，但其影响的机制知之甚少。我们已经表明，中位神经上的Neiguan穴位上的电针（EA）减少了交感神经反射反应。 EA通过涉及MU和Delta受体的阿片机制（RVLM）中的MU和Delta受体，EA抑制了从中位和bl骨（胆囊）神经接收到收敛输入的前交感神经交感神经元神经元。然而，除EA响应中的RVLM外，还可能存在涉及弧形核（ARC）和尾腹外侧周围灰色（PAG）的较长环反射。初步的解剖学和电生理数据表明，这些区域在EA-毛血管反应中起作用。本提案将使用神经解剖学，电生理和药理方法组合来评估ARC和PAG通过三个假设在此反应中的作用。首先，对Neiguan穴位的刺激会增加ARC，PAG和RVLM中的C-FOS免疫反应性，而胆囊的刺激仅在PAG和RVLM中增加C-FOS表达。这些区域中的细胞将是共同标记的，或靠近含有免疫反应性β-内啡肽或Met-Enkephalin的神经元或轴突。其次，EA增加了电弧神经元的活性，该神经元投射到PAG并通过阿片类药物机制促进了PAG内脏的体细胞收敛抑制。第三，pAG中的神经元从中位和斑点神经向RVLM收敛抑制，在那里它们抑制了交感神经前神经元中的诱发活性以及由此产生的心血管反应。了解Neiguan穴位上的EA抑制反射兴奋性心血管反应的途径和中心神经整合，将通过这种替代疗法对对心血管系统的有益调节的基础机制有更深入的了解。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。