Neural Substrates of EA in Cardiovascular Control

EA 在心血管控制中的神经基质

• 批准号: 7878742
• 负责人: John C Longhurst
• 金额: $ 38.07万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878742
• 关键词: Acetylcholine; Acupuncture Points; Acupuncture procedure; Aminobutyric Acids; Animals; Area; Arrhythmia; Blood Pressure; Cannabinoids; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Nucleus; Cholinergic Receptors; Clinical; Clinical Trials; Complement; Country; Data; Disease; Disinhibition; Distal; Educational workshop; Electroacupuncture; Endocannabinoids; Felis catus; Figs - dietary; Gallbladder; Glutamates; Grant; Hypertension; Hypothalamic structure; Infection; Investigation; Ischemia; Knowledge; Lateral; Limb structure; Manuals; Mediating; Medical; Medicine; Meridians; Metabolism; Midbrain structure; Modality; Modeling; Muscarinics; Myocardial Ischemia; N-Methylaspartate; Nerve; Nervous system structure; Neuraxis; Neurons; Neurotransmitters; Opioid; Opioid Receptor; Organ; Pain; Pathway interactions; Patients; Peripheral Nervous System; Physicians; Physiological; Process; Rattus; Reflex action; Regulation; Research; Research Personnel; Role; Scientist; Sensory; Sensory Nerve Endings; Skin; Spinal Cord; Stomach; Structure of nucleus infundibularis hypothalami; System; Testing; Therapeutic; United States; Visceral; Visceral Afferents; base; gamma-Aminobutyric Acid; information processing; interest; midbrain central gray substance; neuromechanism; neurophysiology; nociceptin; prevent; programs; raphe nuclei; receptor; relating to nervous system; response; transmission process

DESCRIPTION (provided by applicant): Acupuncture is an ancient therapeutic modality whose mechanisms of action only recently are being defined. While clinical trials are defining efficacy in areas such as pain, infections and cardiovascular disease, including hypertension, myocardial ischemia and arrhythmias, it is clear that we know little about its mechanisms of action. Over the last three year, this grant has explored the function of a long-loop pathway, including the arcuate nucleus (ARC) in the ventral hypothalamus, the ventrolateral periaqueductal gray (vIPAG) in the midbrain and the rostral ventrolateral medulla (rVLM) in regulation of visceral sympathoexcitatory reflexes. We have demonstrated excitatory input from acupuncture points located along the distal median and deep peroneal somatic nerves activated during electroacupuncture (EA) to the ARC, vIPAG and rVLM. The ARC provides an excitatory projection to the vIPAG, which in turn, provides an inhibitory projection to the rVLM that ultimately regulates sympathetic premotor neurons that innervate the spinal cord sympathetic outflow to the cardiovascular system. The present grant refines and extends our previous observations with three specific aims. The first aim evaluates the significance of reciprocal projections between the ARC and the vIPAG, which we hypothesize, reinforces input in the ARC from somatic afferent stimulation during EA. The second aim identifies the role of specific neurotransmitter systems, including glutamate and its ionotropic receptors in ARC and vIPAG, acetylcholine in ARC and the endocannabinoid system in vIPAG, which we hypothesize, inhibits the release of gamma-aminobutyric acid to disinhibit vIPAG neuronal activity and ultimately potentiate vIPAG inhibition of the rVLM. The third aim examines the role of midline medullary nuclei, especially the nuclei raphe obscurus, magnus and pallidus, which we believe receive excitatory input from the vIPAG and, in turn, inhibit rVLM activity. Studies will use a combination of anatomical, cellular electrophysiological, pharmacological, microcollection-microassay and whole animal reflex approaches to test these hypotheses. This added knowledge will provide physicians and scientists with a greater mechanistic understanding of EA's cardiovascular influence, which will increase its clinical acceptance, e.g., in patients with cardiovascular disease. Furthermore, knowledge of the mechanistic basis of acupuncture may allow practitioners to optimize the clinical cardiovascular responses to treatment.

描述（由申请人提供）：针灸是一种古老的治疗方式，其作用机制直到最近才被确定。虽然临床试验正在确定其在疼痛、感染和心血管疾病（包括高血压、心肌缺血和心律失常）等领域的功效，但显然我们对其作用机制知之甚少。在过去的三年里，这笔赠款探索了长环通路的功能，包括下丘脑腹侧的弓状核（ARC）、中脑的腹外侧导水管周围灰质（vIPAG）和延髓的头端腹外侧延髓（rVLM）。内脏交感兴奋反射的调节。我们已经证明了电针（EA）期间激活的位于远端正中和腓深体神经的穴位对 ARC、vIPAG 和 rVLM 的兴奋性输入。 ARC 向 vIPAG 提供兴奋性投射，而 vIPAG 又向 rVLM 提供抑制性投射，最终调节交感运动前神经元，支配脊髓交感神经流出至心血管系统。目前的资助完善并扩展了我们之前的观察，具有三个具体目标。第一个目标是评估 ARC 和 vIPAG 之间相互投射的重要性，我们假设这会增强 EA 期间体细胞传入刺激对 ARC 的输入。第二个目标是确定特定神经递质系统的作用，包括 ARC 和 vIPAG 中的谷氨酸及其离子型受体、ARC 中的乙酰胆碱和 vIPAG 中的内源性大麻素系统，我们假设它会抑制 γ-氨基丁酸的释放，从而抑制 vIPAG 神经元活动，最终增强 vIPAG 对 rVLM 的抑制。第三个目标是检查中线髓核的作用，特别是中缝暗核、大核和苍白核，我们认为它们接收来自 vIPAG 的兴奋性输入，进而抑制 rVLM 活性。研究将结合解剖学、细胞电生理学、药理学、微量采集微测定和整体动物反射方法来检验这些假设。这些新增知识将使医生和科学家对 EA 对心血管的影响有更深入的机制了解，从而提高其临床接受度，例如在心血管疾病患者中的接受度。此外，对针灸机制基础的了解可以使从业者优化临床心血管对治疗的反应。