Neural Substrates of EA in Cardiovascular Control

描述(由申请人提供)：在过去的三十年里，针灸在美国的使用显著增加。尽管NCCAM正在赞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，但其影响的机制尚不清楚。我们已经证明，电针正中神经上的内关穴可降低交感兴奋心血管反射反应。通过一种阿片机制，涉及延髓头端腹外侧区(RVLM)的Mu和Delta受体，电针抑制运动前交感兴奋神经元，这些神经元接受正中神经和内脏(胆囊)神经的汇聚输入。然而，除了电针反应中的RVLM外，可能还存在涉及弓状核(ARC)和尾侧中脑导水管周围灰质(PAG)的长环反射。初步的解剖学和电生理学数据表明，这些区域在电针心血管反应中发挥作用。本提案将使用神经解剖学、电生理学和药理学相结合的方法，通过三个假说来评估ARC和PAG在这一反应中的作用。首先，刺激内关穴增加了ARC、PAG和RVLm的c-Fos免疫反应，而刺激胆囊穴只增加了PAG和RVLm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的β-内啡肽或甲硫氨酸脑啡肽的神经元或轴突。第二，电针增加投射到PAG的ARC神经元的活动，并通过阿片类机制促进PAG的内脏躯体会聚抑制。第三，PAG中的神经元从正中神经和内脏神经接受会聚抑制，投射到RVLM，在那里它们抑制交感运动前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一替代疗法有益于心血管系统调节的机制。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.