Mechanims of CNS Autonomic Regulation by EA

EA对中枢神经系统自主调节的机制

• 批准号: 8208060
• 负责人: John C Longhurst
• 金额: $ 37.87万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-20 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208060
• 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

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. PUBLIC HEALTH RELEVANCE: Project Narrative Blood pressure abnormalities are major risk factors for coronary artery disease, stroke, congestive heart failure and syncope. However, both hypertension and hypotension are poorly treated because many patients often are unwilling to use standard medical therapy. Today in the US, patients increasingly are looking for integrative therapies that are more acceptable for treatment of their blood pressure abnormality. Although acupuncture may be a viable inexpensive alternative that has a very low incidence of side effects, physicians generally are reluctant to recommend this therapy because little data are available on its efficacy and particularly on its mechanisms of action. The current application will provide important new information on both efficacy and mechanism of action in acupuncture treatment of either elevated or low blood pressure.

描述(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，恶心和呕吐的方法。小型试验进一步表明，电针可以降低升高的血压。在过去的两个赠款周期中进行的研究评估了EA减少交感神经流出和血压升高的能力背后的脊髓上机制。针刺与非特异性刺激躯体交感神经的区别在于其相对的穴位特异性和延缓作用。我们最近展示了穴位特定的血压调制，最大的效果发生在低频率、低强度的电针心包和胃经，特别是在P5-P6和ST36-St37，因为这些穴位为延髓头端腹外侧区(RVLM)的运动前交感神经元提供了重要的输入。我们还证明了阿片类物质，特别是内啡肽和脑啡肽，伤害素和-氨基丁酸(GABA)介导了最初的电针相关的抑制，而阿片类药物和GABA是电针延长血压调节的基础。电针作用于RVLM谷氨酸释放的突触前和突触后，以减少交感神经流出。这一更新扩展了我们的研究，以研究电针通过涉及脊髓、背角和中间外侧柱中的强啡肽和伤害素的作用来调节高血压的节段性。此外，我们最近开始探索针灸在两种反射性血管抑制模型中升高抑郁血压的可能性。第一种是在氯醛糖麻醉的猫体内使用苯双胍(PBG)刺激5-羟色胺-3(5-HT3)受体，通过孤束内侧核(MNTS)和疑核(NA)的通路反射性地降低心率和血压。第二种是氯胺酮-赛拉津麻醉大鼠轻度胃扩张时的反射性心血管抑制，它似乎通过GABAA机制抑制NA的前额神经元和RVLM的交感前神经元，可能起源于尾侧延髓腹外侧部(CVLM)。初步数据表明，电针通过GABA能、5-羟色胺或阿片能机制调节这些心脏降压反射。刺激胃扩张时，电针通过GABA调节mNTS、中缝苍白核和NA的GABA反应。其他具有重要临床意义的研究将探索刺激方式及其潜在机制，包括通过结合两组穴位来实现穴位特异性、频率调制和空间求和。更好地了解针灸通过其脊髓和脊髓上的作用使血压正常化的能力以及潜在的机制，将提供重要的线索，有助于在血压升高或降低的情况下使用针灸，并将有助于西方医学界和科学界更多地接受这种治疗技术。公共卫生相关性：项目简介血压异常是冠状动脉疾病、中风、充血性心力衰竭和晕厥的主要危险因素。然而，高血压和低血压的治疗都很差，因为许多患者往往不愿使用标准的药物治疗。如今，在美国，越来越多的患者正在寻找更容易被接受的综合疗法来治疗他们的血压异常。尽管针灸可能是一种可行的、廉价的、副作用发生率非常低的替代疗法，但医生通常不愿推荐这种疗法，因为关于其疗效，特别是其作用机制的数据很少。目前的应用将为针灸治疗高血压或低血压的疗效和作用机制提供重要的新信息。