Neural Substrates of EA in Cardiovascular Control

描述（由申请人提供）：在过去的三十年中，针灸的使用在美国显着增加。尽管NCCAM正在资助针灸治疗心血管疾病的临床试验，包括高血压、冠状动脉疾病或心律失常，但其影响的潜在机制尚不清楚。我们已经证明电针（EA）在正中神经上的内关穴减少交感神经兴奋性心血管反射反应。EA通过一种阿片机制，包括吻侧腹外侧髓质（rVLM）的mu和delta受体，抑制运动前交感兴奋神经元，这些神经元接受来自正中神经和内脏神经（胆囊）的趋同输入。然而，除了EA反应中的rVLM外，长环反射可能还涉及弓形核（ARC）和尾侧腹外侧导水管周围灰质（PAG）。初步解剖和电生理数据表明，这些区域在ea -心血管反应中起作用。本研究将采用神经解剖学、电生理学和药理学相结合的方法，通过三个假设来评估ARC和PAG在这种反应中的作用。首先，刺激内关穴增加了ARC、PAG和rVLM中c-Fos的免疫反应性，而刺激胆囊只增加了PAG和rVLM中c-Fos的表达。这些区域的细胞要么被共标记，要么靠近含有免疫反应性-内啡肽或-脑啡肽的神经元或轴突。其次，EA增加了ARC神经元的活性，这些神经元投射到PAG，并通过阿片机制促进PAG的内脏躯体收敛抑制。第三，PAG中的神经元受到来自正中神经和内脏神经的收敛性抑制，它们投射到rVLM，在那里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EA内关穴抑制反射性兴奋性心血管反应的通路和中枢神经整合，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，加上目前的临床试验，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。

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.