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: 8011962
• 负责人: John C Longhurst
• 金额: $ 38.25万
• 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/8011962
• 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（由申请人提供）：针灸及其有效的替代方法电针（EA）是公认的治疗疼痛、恶心和呕吐的方法。小试验进一步表明 EA 可以降低高血压。过去两个拨款周期中进行的研究评估了 EA 降低交感神经流出和血压升高能力的脊髓上机制。针灸与非特异性躯体交感神经刺激的区别在于其相对的点特异性和长期作用。我们最近证明了点特异性血压调节，在心包经络和胃经络的低频、低强度 EA 期间，特别是在 P5-P6 和 St36-St37 处，产生最大的效果，因为这些穴位组为延髓头端腹外侧 (rVLM) 的运动前交感神经元提供重要的输入。我们还证明阿片类药物，特别是内啡肽和脑啡肽、伤害感受肽和（GABA）介导最初的 EA 相关抑制，而阿片类药物和 GABA 是 EA 对血压的长期调节的基础。EA 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。这一更新将我们的研究扩展到 研究 EA 通过脊髓背角和中外侧柱中强啡肽和伤害感受肽的作用对血压升高的节段调节。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血压的潜力。第一种方法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-HT3) 心肺受体通过内侧孤束核 (mNTS) 和疑核 (NA) 中的通路反射性降低心率和血压。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，这似乎抑制了前迷走神经 NA 中的神经元和 rVLM 中的前交感神经元通过 GABAA 机制，可能起源于尾部腹外侧延髓 (cVLM)。初步数据表明，EA 在 PBG 刺激期间通过 mNTS、中缝苍白核和 NA 中的 GABA 能、5-HT 或阿片能机制调节这些心脏抑制反射，并通过 胃扩张期间 cVLM 和 NA 中的 GABA。具有重要临床意义的其他研究将调查刺激方式和潜在机制，包括点特异性、频率调制和通过组合两组穴位进行空间求和。更好地了解针灸通过脊柱和脊柱上的作用使血压正常化的能力以及潜在的机制，将为针灸治疗提供重要线索。 针灸在血压升高或降低的情况下的临床应用将有助于提高西方医学和科学界对这种治疗技术的接受度。公众健康相关性：项目叙述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效果不佳，因为许多患者往往不愿意使用标准药物治疗。今天在 在美国，越来越多的患者正在寻找更容易接受的治疗血压异常的综合疗法。 尽管针灸可能是一种可行的廉价替代疗法，而且副作用发生率非常低，但医生通常不愿意推荐这种疗法，因为关于其功效、特别是其作用机制的数据很少。当前的申请将提供有关针灸治疗高或低血压的功效和作用机制的重要新信息。 血压。