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，其作用机制只是最近才被定义。虽然临床试验正在定义疼痛，感染和心血管疾病（包括高血压，心肌缺血和心律失常）等领域的疗效，但很明显，我们对其作用机制知之甚少。在过去的三年里，该基金探索了一个长回路通路的功能，包括腹侧下丘脑的弓状核（ARC），中脑的腹外侧导水管周围灰质（vIPAG）和延髓头端腹外侧（rVLM）在内脏交感神经兴奋性反射的调节中。我们已经证明了兴奋性输入从位于沿着远端正中和腓深体神经电针（EA）激活ARC，vIPAG和rVLM的穴位。ARC向vIPAG提供兴奋性投射，vIPAG又向rVLM提供抑制性投射，rVLM最终调节交感神经前运动神经元，交感神经前运动神经元支配脊髓交感神经流出到心血管系统。目前的赠款完善和扩展了我们以前的观察，有三个具体目标。第一个目标是评估ARC和vIPAG之间相互投射的意义，我们假设这加强了EA期间体细胞传入刺激在ARC中的输入。第二个目的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，我们假设这些系统抑制γ-氨基丁酸的释放以解除vIPAG神经元活性的抑制，并最终增强vIPAG对rVLM的抑制。第三个目的是检查中线髓核的作用，特别是中缝暗核，大核和苍白球，我们认为，从vIPAG接收兴奋性输入，反过来，抑制rVLM活动。研究将使用解剖学、细胞电生理学、药理学、微量收集-微量测定和整个动物反射方法的组合来测试这些假设。这些额外的知识将为医生和科学家提供对EA心血管影响的更深入的机械理解，这将增加其临床接受度，例如，心血管疾病患者。此外，针灸的机械基础的知识，可以让从业者优化治疗的临床心血管反应。