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Mechanims of CNS Autonomic Regulation by EA

EA对中枢神经系统自主调节的机制

基本信息

批准号：
8403737
负责人：
John C Longhurst
金额：
$ 36.05万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-20 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8403737
关键词：
Abdomen Acupuncture Points Acupuncture procedure Adverse effects Afferent Pathways Aminobutyric Acids Animals Antihypertensive Agents Arrhythmia Blood Pressure Bradycardia Butyric Acids C Fiber Cardiac Cardiopulmonary Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cell Nucleus Chemoreceptors Chest Chloralose Clinical Communities Complementary and alternative medicine Congestive Heart Failure Coronary Arteriosclerosis Cutaneous Data Depressed mood Disease Dorsal Dynorphins Electroacupuncture Endorphins Enkephalins Felis catus Fiber Frequencies Funding Gallbladder Glutamates Grant Health Heart Heart Rate Hypertension Hypotension Hypothalamic structure Imagery Incidence Ketamine Manuals Medial Mediating Medical Mental Depression Meridians Midbrain structure Modality Modeling Molecular Myocardial Ischemia Names National Center for Complementary and Alternative Medicine Nausea and Vomiting Nerve Neuraxis Neurons Neurotransmitters Nucleus solitarius Opioid Opioid Receptor Pain Pathway interactions Patients Peptide Receptor Pericardial body location Peripheral Physicians Rattus Reflex action Regulation Relative (related person)Research Risk Factors Role Serotonin Site Skin Specificity Spinal Spinal Cord Spinal Cord Column Spinal cord posterior horn Stomach Stroke Structure of radial nerve Syncope System Techniques Text Therapeutic Thoracic spinal cord structure United States Visceral Work Xylazine chronotropic clinically relevant design dorsal horn gamma-Aminobutyric Acid improved interest neuromechanism nociceptin nucleus ambiguus peroneal nerve phenyl biguanide raphe nuclei receptor relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): Acupuncture and its potent alternative, electroacupuncture (EA), are accepted treatments for pain, nausea and vomiting. Small trails further suggest that EA can lower elevated blood pressure. Studies conducted in the last two grant cycles have evaluated supra-spinal mechanisms underlying EA's ability to reduce elevated sympathetic outflow and blood pressure. Acupuncture is differentiated from non-specific somatosympathetic stimulation by its relative point specificity and its prolonged action. We recently demonstrated point specific blood pressure modulation with the largest effect occurring during low frequency, low intensity EA at the pericardial and stomach meridians, specifically at P5-P6 and St36-St37, since these sets of acupoints provide significant input to premotor sympathetic neurons in the rostral ventrolateral medulla (rVLM). We also have demonstrated that opioids, specifically endorphins and enkephalin, nociceptin and (-amino butyric acid (GABA), mediate the initial EA-related inhibition while opioids and GABA underlie prolonged modulation of blood pressure by EA. EA works both pre- and post- synaptically on rVLM glutamate release, to lower sympathetic outflow. This renewal extends our studies to investigate EA segmental regulation of elevated blood pressure through actions involving dynorphin and nociceptin in the spinal cord dorsal horn and intermediolateral columns. In addition, we recently have begun to explore the potential for acupuncture to elevate depressed blood pressure in two models of reflex vasodepression. The first uses phenylbiguanide (PBG) in chloralose anesthetized cats to stimulate 5- hydroxytryptamine-3 (5-HT3) cardiopulmonary receptors to reflexly lower heart rate and blood pressure through pathways in the medial nucleus tractus solitarii (mNTS) and nucleus ambiguus (NA). The second involves reflex cardiovascular depression during mild gastric distension in ketamine-xylazine anesthetized rats, which appears to inhibit the prevagal neurons in the NA and presympathetic neurons in the rVLM through a GABAA mechanism, likely originating from the caudal ventrolateral medulla (cVLM). Preliminary data suggest that EA modulates these cardiodepressor reflexes through GABAergic, 5-HT or opioidergic mechanisms in the mNTS, nucleus raphe pallidus and NA during PBG stimulation and through GABA in the cVLM and NA during gastric distension. Additional studies, which have important clinical implications, will investigate stimulation modality and the underlying mechanisms, including point specificity, frequency modulation and spatial summation by combining two sets of acupoints. An improved understanding of acupuncture's ability to normalize blood pressure through its spinal and supraspinal actions, as well as underlying mechanisms, will provide important clues that can assist in the clinical use of acupuncture in conditions of either elevated or depressed blood pressure and will contribute to increased acceptance of this therapeutic technique by the western medical and scientific communities.

描述（由申请人提供）：针灸及其有效的替代品，电针（EA），是公认的治疗疼痛，恶心和呕吐。小试验进一步表明，EA可以降低血压升高。在过去的两个资助周期进行的研究已经评估了超脊髓机制的基础EA的能力，以减少升高的交感神经流出和血压。针刺与非特异性躯体交感神经刺激的区别在于其相对的穴位特异性和作用时间的延长。我们最近证明了点特定的血压调制与最大的影响发生在低频率，低强度EA在心包和胃的经络，特别是在P5-P6和St 36-St 37，因为这些组的穴位提供了显着的输入到运动前交感神经元在延髓头端腹外侧（rVLM）。我们也已经证明，阿片类药物，特别是内啡肽和脑啡肽，痛敏素和β-氨基丁酸（GABA），介导的初始EA相关的抑制，而阿片类药物和GABA的基础上延长调制的血压EA。电针在突触前和突触后作用于rVLM谷氨酸释放，以降低交感神经流出。这一更新扩展了我们的研究，以探讨EA节段性调节血压升高，通过涉及脊髓背角和中间外侧柱的强啡肽和痛敏素的行动。此外，我们最近已经开始探索针灸在两种反射性血管抑制模型中升高血压的潜力。第一种是在氯醛糖麻醉的猫中使用苯基双胍（PBG）来刺激5-羟色胺-3（5-HT 3）心肺受体，以通过内侧孤束核（mNTS）和疑核（NA）中的通路反射性地降低心率和血压。第二个涉及氯胺酮-甲苯噻嗪麻醉大鼠轻度胃扩张期间的反射性心血管抑制，其似乎通过GABAA机制抑制NA中的迷走神经前神经元和rVLM中的前交感神经元，可能源自尾侧腹外侧髓质（cVLM）。初步数据表明，EA调节这些心脏降压反射通过GABA能，5-HT或阿片类药物的机制，在mNTS，中缝苍白核和NA在PBG刺激和通过GABA的cVLM和NA在胃扩张。具有重要临床意义的其他研究将研究刺激方式和潜在机制，包括结合两组穴位的点特异性，频率调制和空间总和。对针灸通过其脊柱和脊髓上作用使血压正常化的能力以及潜在机制的进一步了解，将提供重要的线索，可以帮助针灸在血压升高或降低的情况下的临床应用，并将有助于增加西方医学和科学界对这种治疗技术的接受。