Mechanisms of CNS Autonomic Regulation by Acupuncture

针灸调节中枢神经系统自主神经的机制

• 批准号: 9243979
• 负责人: Zhi-Ling Guo
• 金额: $ 34.76万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243979
• 关键词: Acupuncture Points; Acupuncture Therapy; Acute; Adenosine; Adenosine A1 Receptor; Adverse effects; American; Anatomy; Aneurysm; Antihypertensive Agents; Area; Attenuated; Axon; Biochemical; Blood Pressure; Brain Stem; Butyric Acids; Cardiovascular Physiology; Cardiovascular system; Cell Nucleus; Cephalic; Chemicals; Chronic; Clinical; Coronary Arteriosclerosis; Data; Disease; Ear; Ear Acupuncture; Electric Stimulation; Electroacupuncture; Electrophysiology (science); Enkephalins; Essential Hypertension; Fiber; Funding; Grant; Heart; Heart failure; Hyperactive behavior; Hypertension; Hypothalamic structure; Incidence; Knowledge; Location; Manuals; Mechanical Stimulation; Mechanics; Mediating; Mediation; Medical; Midbrain structure; Modality; Modeling; Molecular; Morbidity - disease rate; Myocardial Ischemia; Nerve; Nerve Fibers; Neuromodulator; Neurotransmitters; Nucleus solitarius; Opioid; Opioid Receptor; Patients; Peripheral; Pharmacology; Physicians; Physiological; Purinoceptor; Rattus; Reflex action; Regulation; Role; Rupture; Sensory; Sensory Receptors; Spinal Ganglia; Stroke; Thinness; United States National Institutes of Health; Vanilloid; afferent nerve; aged; blood pressure reduction; clinical practice; gamma-Aminobutyric Acid; hypertension treatment; improved; insight; mortality; neuromechanism; novel; public health relevance; receptor; response; somatic afferent nerve

 DESCRIPTION (provided by applicant): We are investigating mechanisms by which acupuncture regulates cardiovascular function, focusing on its modulation of elevated blood pressure (BP). Electroacupuncture (EA) is capable of lowering acute and chronic elevations in BP and alleviating demand-induced myocardial ischemia. Acupuncture's actions are slow in onset, but the duration of action is prolonged. We have been funded previously to study neural mechanisms underlying acupuncture's cardiovascular effects. Although these studies have shown that both EA and manual acupuncture (MA) applied at acupoints overlying somatic afferent nerves attenuate cardiovascular sympathoexcitatory responses, the mechanisms by which various forms of acupuncture application activate sensory nerve fibers to lower elevated BP are largely unknown. In this regard, although EA and MA activate sensory nerves through electrical and mechanical stimulation, it is unclear whether these modalities stimulate sensory afferent nerves and their perikarya in dorsal root ganglia through direct depolarization of fibers in passage or through a chemical intermediate mediated by a receptor specific mechanism, such as transient receptor potential vanilloid type-1 (TRPV1) or ATP purinergic receptors. Our studies also have demonstrated that, following stimulation of sensory nerves, EA lowers reflex elevations in BP through opioids by modulating presympathetic activity in the rostral ventrolateral medulla (rVLM), a brain stem nucleus that importantly controls sympathetic outflow and hence cardiovascular function. However, it is unclear if opioids act alone or mediate the actions of other cardiovascular-suppressing neuromodulators like adenosine or γ-amino butyric acid (GABA) to facilitate the action of acupuncture in lowering elevated BP during cardiovascular excitatory responses as well in sustained hypertension. Additionally, there is no information available on the role of opioids and other neurotransmitters in lowering elevated BP with acupuncture applied at locations other than somatic acupoints, like auricular acupuncture (AA). In this respect, manual and electrical AA applied at "the heart point" in the ear, which likey activates vagal afferent nerves projecting to the medulla, is used empirically to manage elevated BP. However, medullary mechanisms underlying AA's hypotensive actions remain unknown. The central hypothesis of this application is that acupuncture at somatic and cranial vagal nerve acupoints lowers elevated BP by modulating rVLM presympathetic activity through opioid- mediated mechanisms, by stimulating sensory receptors (MA) or thin fiber axons in passage (EA). The present grant focuses on four new areas: 1) electrical and mechanical-chemical sensory neural mechanisms by which EA and MA inhibit cardiovascular function; 2) the role of rVLM adenosine in opioid mediation of acupuncture inhibition of excitatory cardiovascular reflex responses; 3) acupuncture's action in lowering BP in sustained hypertension through medullary enkephalins and adenosine and 4) medullary mechanisms of auricular acupuncture in modulating elevated BP through actions of opioids and GABA. Anatomical, biochemical, physiological, electrophysiological, pharmacological and molecular approaches will be used in the proposed studies that are highly relevant to patients with hypertension and sympathetic hyperactivity, who have the potential to benefit from clinical acupuncture.

 描述（由申请人提供）：我们正在研究针灸调节心血管功能的机制，重点关注其对血压（BP）的调节，电针（EA）能够降低血压的急性和慢性升高，并缓解需求引起的心肌升高。针灸的作用起效缓慢，但作用持续时间较长。研究表明，在躯体传入神经上方的穴位应用电针和手法针灸 (MA) 都会减弱心血管交感兴奋反应，但各种形式的针灸应用激活感觉神经纤维以降低升高的血压的机制在很大程度上尚不清楚。 EA和MA通过电和机械刺激激活感觉神经，目前尚不清楚这些方式是否刺激背根神经节的感觉传入神经及其核周通过通道中纤维的直接去极化或通过受体特异性机制介导的化学中间体，例如瞬时受体电位香草酸1型（TRPV1）或ATP嘌呤受体我们的研究还表明，在刺激感觉神经后，EA。通过阿片类药物调节延髓头端腹外侧 (rVLM) 的前交感神经活动，降低血压反射性升高，rVLM 是脑干核，重要控制交感神经流出，从而控制心血管然而，目前尚不清楚阿片类药物是否单独起作用或介导其他心血管抑制神经调节剂（如腺苷或γ-氨基丁酸（GABA））的作用，以促进针灸在心血管兴奋反应期间以及持续期间降低血压的作用。此外，没有关于阿片类药物和其他神经递质在通过针灸除躯体穴位以外的部位降低血压方面的作用的信息。耳针（AA）在这方面，在耳朵的“心脏点”应用手动和电耳针，这可能会激活投射到髓质的迷走神经传入神经，被经验性地用于控制血压升高。降血压作用尚不清楚，该申请的中心假设是针灸躯体和颅迷走神经穴位通过调节来降低血压升高。 rVLM 通过阿片类药物介导的机制，通过刺激通道中的感觉受体 (MA) 或细纤维轴突 (EA) 来发挥前交感神经活性。目前的资助重点关注四个新领域：1) EA 和 MA 所采用的电和机械化学感觉神经机制。抑制心血管功能；2) rVLM 腺苷在阿片类药物介导的针灸抑制兴奋性心血管反射反应中的作用；3) 针灸通过降低持续性高血压的血压作用；髓质脑啡肽和腺苷以及 4) 耳针通过阿片类药物和 GABA 的作用调节血压升高的髓质机制将用于与高血压患者高度相关的拟议研究。和交感神经亢进，他们有可能从临床针灸中受益。